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Fbxo7 gets proactive with cyclin D/ cdk6. Paper-11361781.
CAK-independent activation of CDK6 by a viral cyclin. Paper-9145950.
The increased p27Kip1 bound preferentially to CDK6. Paper-995380.
Expression of p19INK4d, CDK4, CDK6 in glioblastoma multiforme. Paper-8397413.
There was no evidence for involvement of CDK4 or CDK6 in the blockade. Paper-1341485.
Recombinant p18 inhibits the kinase activity of cyclin D- CDK6. Paper-144006.
Identification of G1 kinase activity for cdk6, a novel cyclin D partner. Paper-113104.
Cyclin D1 binds to the Cdk4 and Cdk6 to form a pRB kinase. Paper-13178259.
We found that most variants were deficient in interaction with Cdk4 and Cdk6. Paper-368362.
This diminution of function was independent of CDK4 and CDK6 binding ability. Paper-1904097.
Regulation of cyclin dependent kinase 6 by microRNA 124 in medulloblastoma. Paper-12976346.
Moreover, CDK6 (but not CDK4) was detectable in all the populations investigated. Paper-936644.
The p16(INK4a) tumor suppressor inhibits cyclin-dependent kinases ( CDK4 and CDK6). Paper-2050306.
Downregulation of CCND1 and CDK6 by miR-34a induces cell cycle arrest. Paper-14309110.
Crystal structure of a viral cyclin, a positive regulator of cyclin-dependent kinase 6. Paper-8323611.
Interestingly, upregulation of either cdk4 or cdk6 was demonstrated in 85% of cases. Paper-1253721.
Modulation of beta-catenin by cyclin-dependent kinase 6 in Wnt-stimulated cells. Paper-12441209.
Caspases 3 and 8 were strongly activated while the amount of CDK6 was reduced by TNF-alpha. Paper-10559179.
The amounts of cdk4, cdk6, and the D type cyclins are not affected by 18 h of hypoxia. Paper-9515173.
Viral cyclin- cyclin-dependent kinase 6 complexes initiate nuclear DNA replication. Paper-8689567.
Furthermore, p18Ink4c inhibits CDK6 phosphorylation and activation by CAK. Paper-880241.
Normal melanocytes and all melanoma lines expressed Cdk4, Cdk6, and cyclins D1 and D3. Paper-827203.
The dephosphorylation of Cdk2 and Cdk6 by PP2C isoforms was inhibited by the binding of cyclins. Paper-8606392.
Overexpression of cyclin D1, CDK4, and CDK6 showed an association with normal Rb expression. Paper-12328674.
A novel cytoplasmic substrate for cdk4 and cdk6 in normal and malignant epithelial derived cells. Paper-418244.
Levels and activities of CDK6, cyclin A, and cyclin D1 were all suppressed by trastuzumab. Paper-12190201.
CDK4 and CDK6 delay senescence by kinase-dependent and p16INK4a-independent mechanisms. Paper-13260835.
The amount of p16INK4A, p21CIP1, p18INKAC and CDK6 was variable from one cell line to the other. Paper-8845289.
Furthermore, temporal alterations in the association of PCNA with p21 and with CDK6 were observed. Paper-562482.
We find that KSHV-cyclin can activate CDK6 independent of phosphorylation by CAK in vitro. Paper-9145950.
Its product inhibits the phosphorylation of the retinoblastoma protein (pRb) by CDK4 and CDK6. Paper-485804.
Thus, p16 mutant proteins that retain CDK4 and CDK6 binding may have more subtle functional defects. Paper-2000990.
The control of Cdk6 expression mediated by TDP-43 involves GT repeats in the target gene sequence. Paper-14293770.
Structural analysis of the inhibition of Cdk4 and Cdk6 by p16(INK4a) through molecular dynamics simulations. Paper-9643459.
In addition, CAK phosphorylation decreased the p16(INK4a) sensitivity of CDK6/KSHV-cyclin complexes. Paper-9145950.
We showed that CCND1- CDK6 phosphorylates beta-catenin on serine 45 (S45). Paper-12441209.
A possible mode of binding between p19(INK4d) and CDK4 and CDK6 could therefore involve the loop segments of p19(INK4d). Paper-1602091.
Overexpression of E2F1, cyclin D1, CDK4, and CDK6 was detected in 50.7%, 24.3%, 92.1%, and 10.5%, respectively. Paper-12328674.
Cdk6- cyclin D3 complex evades inhibition by inhibitor proteins and uniquely controls cell's proliferation competence. Paper-8838635.
Interestingly, CDK6 kinase activity was dramatically elevated due to high levels of cyclin D3 in association with CDK6. Paper-1493351.
The other INK4 family members form stable complexes with CDK6 but associate only transiently with CDK4. Paper-1767478.
Growth suppression by p18, a p16INK4/MTS1- and p14INK4B/ MTS2-related CDK6 inhibitor, correlates with wild-type pRb function. Paper-144006.
Both cdk4 and cdk6 phosphorylate the retinoblastoma protein (pRb) and are thought to be required for cell proliferation. Paper-533637.
Cdk6 blocks myeloid differentiation by interfering with Runx1 DNA binding and Runx1-C/EBPalpha interaction. Paper-13219214.
Analysis of proteins that co-immunoprecipitated with cdk6 showed that the 450 kDa complex contained both Hsp90 and CDC37. Paper-1328676.
Cell cycle and biochemical effects of PD 0183812. A potent inhibitor of the cyclin D-dependent kinases CDK4 and CDK6. Paper-8958178.
The D-type cyclin-dependent kinases CDK4 and CDK6 are complexed with many small cellular proteins (p14, p15, p16, p18, and p20). Paper-144006.
Removal of TDP-43 in human cells significantly increases cyclin-dependent kinase 6 ( Cdk6) protein and transcript levels. Paper-14293770.
D type cyclins interact with CDK4 and CDK6 to drive the progression of a cell through early/mid-G(1)in response to mitogen stimulation. Paper-9998626.
Immunohistochemistry revealed strong expression of PPM1D in 148 (88%) of 168 and CDK6 in 50 (30%) of 169 medulloblastomas. Paper-11164350.
This G(1) arrest is associated with inhibition of cyclin D3/ cdk6-mediated retinoblastoma protein phosphorylation by p18(INK4c). Paper-8624059.
All three D-type cyclins can be shown to associate with two specific kinases, cdk4 and cdk6, providing at least six possible combinations. Paper-120238.
The homologous cyclin-dependent kinases (CDK) CDK4 and CDK6 integrate mitogenic and oncogenic signaling cascades with the cell cycle. Paper-13886819.
Cyclin D/ CDK4 and CDK6 may conceivably also be activated by Myc, but the circumstances in which this occurs remain to be explored. Paper-11656255.
Although all three D cyclins bind and activate cdks 2, 4 and 6, Fbxo7 has been characterised as a selective enhancer of cdk6 activity. Paper-11361781.
We have isolated cDNA sequences corresponding to the MTS2 genomic fragment that encodes the CDK4- and CDK6-associated p14 protein. Paper-144006.
This timing suggests that cdk6, and by analogy its homolog cdk4, links growth factor stimulation with the onset of cell cycle progression. Paper-113104.
In vitro binding experiments established that the P48L mutant protein does not bind to cdk4 or cdk6 and thus is functionally abnormal. Paper-1937030.
The crystal structure of the cyclin D-dependent kinase Cdk6 bound to the p19 INK4d protein has been determined at 1.9 A resolution. Paper-1578318.
Immunohistochemical stains for proteins Rb, E2F1, cyclin D1, CDK4, CDK6, p16, and p27 were carried out on tissue microarrays. Paper-12328674.
There was also an increased binding of p16 to the Cdk6 kinase in senescent cells, and a decreased Cdk6 as well as Cdk2 kinase activity. Paper-1529407.
As a result, trastuzumab inhibited Rb phosphorylation that associates with CDK2, cyclin E, CDK6, cyclin A, or cyclin D1. Paper-12190201.
Immunocomplex Western blotting demonstrated increased association of p21 with CDK2 and CDK6 in A431 cells treated with 2.5 nm EGF. Paper-562482.
This phosphorylation is thought to contribute to the derepression of E2F-responsive genes and to be mediated, in part, by Cdk4 and Cdk6. Paper-8661771.
Rodent fibroblasts engineered to overexpress both Cdk6 and cyclin D3 highly resist serum starvation- or cell-cell contact-imposed G(1)-arrest. Paper-8838635.
Furthermore, increased protein-levels of PPM1D and CDK6 may link the TP53 and RB1 tumor suppressor pathways to medulloblastoma pathomechanisms. Paper-11164350.
Cyclin-dependent kinase 6 associates with the androgen receptor and enhances its transcriptional activity in prostate cancer cells. Paper-10784041.
Moreover, purified recombinant PP2C alpha and PP2C beta 2 proteins efficiently dephosphorylated monomeric Cdk2/ Cdk6 in vitro. Paper-8606392.
We demonstrate that the kinase activity associated with KSHV-cyc is sensitive to the cdk inhibitor p27 ( KIP) and due to activation of cdk6. Paper-1014651.
An immunoprofile of HGF, CDK6 and MET revealed a strong correlation between aCGH and immunohistochemical protein expression for CDK6 (P = 0.002). Paper-12821658.
TDP-43 regulates retinoblastoma protein phosphorylation through the repression of cyclin-dependent kinase 6 expression. Paper-14293770.
We have found that the Cdk6- cyclin D3 complex is unique among the D cyclin and kinase combinations in the ability to promote the cell cycle start. Paper-8838635.
CDK6 and p27 showed correlation with the histologic grade of the sarcomas, suggesting that these proteins could be used as prognostic markers. Paper-12328674.
Importantly, CDK6 cannot substitute for CDK4 in this role, which demonstrates that the 2 cyclin D-dependent kinases are functionally different. Paper-8533594.
Bone morphogenetic protein 2- induced osteoblast differentiation requires Smad- mediated down-regulation of Cdk6. Paper-10344140.
Our data strongly indicate that CDK6 is regulated by microRNA 124 in medulloblastoma and that miR 124 modulates medulloblastoma cell growth. Paper-12976346.
Here, c-Myb was identified as part of a protein complex from human T cells containing the cyclin-dependent kinase ( CDK) CDK6. Paper-10733463.
Tax stimulates the cell cycle in the G(1) phase by activating the cyclin-dependent kinase ( CDK) CDK4 and CDK6 holoenzyme complexes. Paper-9441141.
Hence, both the cyclin D1 and D3 as well as CDK4 and CDK6 subunits can confer substrate specificity on the overall cyclin D- CDK complex. Paper-1277357.
CDK6 is present in the chromatin structure of these cells in association with the AR and the promoter region of the prostate-specific antigen gene. Paper-10784041.
In contrast to CDK4, CDK6 does not contain such a proline and, unexpectedly, remained poorly phosphorylated and active in a variety of cells. Paper-13886819.
1. Cyclin D1, a candidate gene of that region was overexpressed in all tumor-derived cells but cyclinD1/ cdk4/ cdk6 kinase activity was not increased. Paper-8307430.
The T877A mutant of the AR frequently found in advanced cases of prostate cancer displays an exaggerated stimulation of transcriptional activity by CDK6. Paper-10784041.
These data attest to the functional importance of both CDK4 and CDK6 in astrocytic tumourigenesis, particularly during the later stages of tumour progression. Paper-8397413.
The p16Ink4/ CDKN2, D-type cyclins, their partners Cdk4/ Cdk6, and pRb constitute a G1 regulatory pathway commonly targeted in tumorigenesis. Paper-827203.
The tumor suppressor p16(INK4A) inhibits phosphorylation of pRb by CDK4 and CDK6 and can thereby block cell cycle progression at the G(1)/S boundary. Paper-8662454.
Despite the sequence and functional homology between CDK4 and CDK6, the role of germline mutations in CDK6 in melanoma predisposition is unknown. Paper-8498044.
The absence of p16 correlated with the phosphorylation of the retinoblastoma protein on cyclin D/ CDK4- or cyclin D/ CDK6-specific sites. Paper-13294476.
BACKGROUND: D-type cyclins, in association with the cyclin-dependent kinases CDK4 and CDK6, promote progression through the G1 phase of the cell cycle. Paper-1632282.
Both in vivo and in vitro, p18 interacts strongly with CDK6, weakly with CDK4, and exhibits no detectable interaction with the other known CDKs. Paper-144006.
Immunoprecipitation of CDK4 and CDK6 and their associated proteins from radiolabeled extracts from senescent HDFs showed no other CDK inhibitors. Paper-811959.
Cdc37 protein specifically interacts with Cdk4 and Cdk6, but not with Cdc2, Cdk2, Cdk3, Cdk5 and any of a number of cyclins tested. Paper-1007090.
PEG10, but not CDK14 or CDK6, was significantly overexpressed in 30 of 41 tumors (73%) from HCC patients, compared with their nontumorous counterparts. Paper-14694899.
Substitution of aspartic acid 92 by alanine instead increases the binding of the peptide to cdk4 and cdk6 and the kinase inhibitory activity. Paper-1328674.
All of the CDK6 and half of the CDK4 were complexed with p18 in terminally differentiated C2C12 cells as well as in adult mouse muscle tissue. Paper-887807.
CDK6 expression revealed a positive correlation with the histologic grade of the sarcoma, and p27 expression was inversely correlated with sarcoma grade. Paper-12328674.
These data suggest that even though there are cdk6/ cyclin D complexes detectable in both the cytoplasm and nucleus, only the cdk6 that is in the nucleus is active. Paper-1328676.
D-type cyclins bind to and activate the cyclin-dependent kinases Cdk4 and Cdk6, which in turn phosphorylate their downstream target, the retinoblastoma protein Rb. Paper-9313391.
In the present study, we show that ectopic expression of miR-34a reduces both mRNA and protein levels of cyclin D1 ( CCND1) and cyclin-dependent kinase 6 ( CDK6). Paper-14309110.
However, fetal adrenal Cdk2, Cdk4, and Cdk6 mRNA levels and protein immunoexpression were similar in the baboon fetal adrenal at early-, mid-, and late gestation. Paper-12397233.
We also demonstrate that miR-34a targets the 3'-untranslated mRNA region of CCND1 as well as CDK6, which in turn interferes with phosphorylation of retinoblastoma. Paper-14309110.
Immunodepletion analysis of p21 and p16 from the senescent cell extracts revealed that p16 is the major CDK inhibitor for both CDK4 and CDK6 kinases. Paper-811959.
The enforced expression of Cdk6 blocked BMP-2-induced osteoblast differentiation to various degrees, depending on the level of its overexpression. Paper-10344140.
In MNNG-transformed cells select cyclin D1-CDK6-CDI and cyclin D1-CDK2-CDI protein complexes were altered but CDK6 and CDK4 kinase activity remained unaffected. Paper-1493351.
Although CDK4 and CDK6 and their INK4-insensitive variants can extend the life span of HDFs, they also cause a substantial increase in the levels of endogenous p16(INK4a). Paper-13260835.
On the other hand, cycling Cdks such as Cdk2, Cdk4 and Cdk6, initiate death pathways by derepressing E2F-1/Rb-dependent transcription at the neuronal G1/S checkpoint. Paper-9653660.
Other amplified regions containing well-known oncogenes in GBMs were also detected at 7p12 ( EGFR), 7q21 ( CDK6), 4q12 ( PDGFRA), and 12q13-15 ( MDM2 and CDK4). Paper-12256696.
Within 17q23.2-qter and 7q21.2, two of the most frequently gained chromosomal regions, confined amplicons were identified that contained the PPM1D and CDK6 genes, respectively. Paper-11164350.
We propose that Cdk6 downregulation in myeloid progenitors releases Runx1 from Cdk6 inhibition, thereby allowing terminal differentiation. Paper-13219214.
PP2C alpha and PP2C beta 2 co-purified with Mg(2+)-dependent Cdk2/ Cdk6 phosphatase activity in DEAE-Sepharose, Superdex-200, and Mono Q chromatographies. Paper-8606392.
End-stage differentiation of neutrophil granulocytes in vivo is accompanied by up-regulation of p27kip1 and down-regulation of CDK2, CDK4, and CDK6. Paper-10390757.
Moreover, we found that PU.1, an Ets transcription factor that is oncogenic in erythroid cells and also can block their differentiation, controls the synthesis of CDK6 mRNA. Paper-9757807.
CONCLUSIONS: Our results indicate that in immature human BFU-E, TNF-alpha downregulates CDK6 but also directly produces apoptosis which is prevented by SCF. Paper-10559179.
Significantly, p16(INK4a) itself does not appear to form higher-order complexes, and the overwhelming majority remains either free or forms binary associations with CDK4 and CDK6. Paper-1767498.
Chemical modification resulted in the identification of PD 0183812 as a potent and highly selective inhibitor of both CDK4 and CDK6 kinase activity, which is competitive with ATP. Paper-8958178.
Chromosomal mapping of members of the cdc2 family of protein kinases, cdk3, cdk6, PISSLRE, and PITALRE, and a cdk inhibitor, p27Kip1, to regions involved in human cancer. Paper-177874.
Mutational analyses showed that highly conserved amino acids in the cyclin box of v-cyclin were important for association with cdk6 and for activation of cdk6 kinase activity. Paper-135952.
These results suggest that cooperation of Bcl-xL, Cdk4, and Cdk6 induced by CD40 signaling plays a key role in CD40-mediated selective growth of B cells. Paper-432598.
It is, however, surprising that this association has not been previously uncovered and that it is apparently not shared with cdk4, long understood to be a functional homolog of cdk6. Paper-11361776.
The 450 kDa complex was shown to be predominantly cytoplasmic, whereas the 170 kDa cyclin D/ cdk6 and the 50-70 kDa complexes were present in both nuclear and cytoplasmic compartments. Paper-1328676.
Furthermore, Wnt3a-stimulated cytosolic beta-catenin levels were higher in CDK6 knockout mouse embryonic fibroblasts (CDK6-/- MEFs) compared to wild-type MEFs. Paper-12441209.
1. Cdk6 inhibits Runx1 activity by binding to the runt domain of Runx1, interfering with Runx1 DNA binding and Runx1-C/EBPalpha interaction. Paper-13219214.
The cyclin encoded by Kaposi's sarcoma-associated herpesvirus stimulates cdk6 to phosphorylate the retinoblastoma protein and histone H1. Paper-1014651.
miR-449a and miR-449b are direct transcriptional targets of E2F1 and negatively regulate pRb- E2F1 activity through a feedback loop by targeting CDK6 and CDC25A. Paper-14053452.
These findings suggest that CDK6 may play an important role in the development and/or progression of a subset of human prostate cancers by stimulating the activity of the AR. Paper-10784041.
Here we demonstrate that cyclin-dependent kinase 6 ( CDK6), in association with cyclin D1 ( CCND1), directly binds to beta-catenin. Paper-12441209.
These results provide the grounds for new therapeutic strategies in ALL either targeting the epigenetic regulation of microRNAs and/or directly targeting the CDK6- Rb pathway. Paper-13774373.
In this study we have surveyed by immunoblotting the protein levels of Cyclin D1, D2, D3 and their catalytic partners, Cdk4 and Cdk6 in normal and transformed human cells. Paper-129183.
Functional analyses for the selected genes proved that these miRNAs act on C-MYC, E2F3, CDK6 and TGIF2, resulting in metastasis through aberrant methylation of the miRNAs. Paper-13509763.
Differential regulation of cyclin-dependent kinase 4 ( CDK4) and CDK6, evidence that CDK4 might not be activated by CDK7, and design of a CDK6 activating mutation. Paper-13886819.
In human immature BFU-E tumor necrosis factor-alpha not only downregulates CDK6 but also directly produces apoptosis which is prevented by stem cell factor. Paper-10559179.
RESULTS: cDNA array analysis showed that cyclin B1, MCM5, MCM7, RAD9, ubiquitin C, CDK6, SKP2, and APAF1 were up-regulated in malignant thyroid neoplasms. Paper-11848311.
Glucocorticoids induced a significant decrease in the percentage of cells in S-phase and in CDK1, CDK4 and CDK6 expression and an increase in the percentage of cells in subG1 peak. Paper-8458678.
Cdk6- mediated inhibition of granulocytic differentiation could be reversed by excess Runx1, consistent with Runx1 being the major target for Cdk6. Paper-13219214.
The 1p35-p31 region contains an excellent candidate tumor suppressor gene, p18, whose product is a cell cycle regulator that inhibits the cyclin D1- associated kinase CDK6. Paper-1228568.
SHP-1 knockdown decreases the CDK6 levels, inducing retinoblastoma protein hypophosphorylation, downregulation of cyclin E and thereby a decrease in the CDK2 activity. Paper-14214856.
Together, these data indicate that EVI1 activation is likely due not to the generation of a novel fusion gene with CDK6 but to a position effect dysregulating its transcriptional pattern. Paper-10350544.
Reverse transcriptase polymerase chain reaction ( RT-PCR) analysis showed overexpression of EVI1 in both cases, but excluded the presence of any CDK6/ EVI1 fusion transcript. Paper-10350544.
Furthermore, the activities of CDK2, CDK4- and CDK6- associated kinase were reduced and the lack of the CDK activity was paralleled by increased hypophosphorylation of Rb protein. Paper-9768567.
Distinct from the p21/p27 family of CDK inhibitors that form ternary complexes with cyclin-CDKs, only binary complexes of p14, p16, and p18 were found in association with CDK4 and/or CDK6. Paper-144006.
Cdk7 phosphorylates Cdk1, Cdk2, Cdk4, and Cdk6, but only Cdk1 and Cdk2 can phosphorylate Cdk7 and none of them is able to auto-phosphorylate. Paper-13231176.
Finally, kinase activity of CDK2 and CDK4 decreases as C2C12 cells differentiate, whereas the CDK6 kinase activity is low in both proliferating myoblasts and differentiated myotubes. Paper-887807.
Therefore, testicular GCTs were analyzed as to the expression of CDK2, CDK4, CDK6, and the expression of their catalytic partners cyclins D1, D2 and E by semiquantitative reverse transcription-PCR. Paper-8840207.
In murine C2C12 myoblast cells, G1 CDK enzymes ( CDK2, CDK4, and CDK6) associate with four CDK inhibitors: p18INK4c, p19INK4d, p21, and p27Kip1. Paper-887807.
Thus, CAK phosphorylated K cyclin/ cdk6 targets multiple sites in the retinoblastoma protein ( pRb) whereas the unphosphorylated complex targets a single site. Paper-8845728.
Surprisingly however, this could not explain arrest, since expression of mutant CDK4 and/or CDK6, incapable of binding p16(Ink4a), did not confer any greater lifespan extension than the wild-type CDKs. Paper-9494886.
The amino acid substitutions in mutants G101W and H83Y not only disrupted CDK4 and CDK6 binding, but decreased the protein half-lives by two- and three-fold, respectively, compared to wt p16. Paper-1181183.
Western blot analysis of cyclin D1 immunoprecipitates indicated complex formation with both cyclin-dependent kinase 4 ( Cdk4) and cyclin dependent kinase 6 ( Cdk6). Paper-2086842.
The results also indicate that CDK4 and CDK6 are functionally distinct and support our hypothesis that the two CDKs regulate cell division at different stages of erythroid maturation. Paper-8563109.
Indole-3-carbinol inhibits the expression of cyclin-dependent kinase-6 and induces a G1 cell cycle arrest of human breast cancer cells independent of estrogen receptor signaling. Paper-1344465.
However, in contrast to cdk6 activated by cellular type D cyclins, the cdk6 activated by KSHV-cyc is capable of phosphorylating not only the retinoblastoma protein but also histone H1. Paper-1014651.
As expected, induction of p16(INK4a) results in a G1 cell cycle arrest by inhibiting phosphorylation of the retinoblastoma protein (pRb) by the cyclin-dependent kinases CDK4 and CDK6. Paper-1767498.
Some of the candidate target genes of amplification ( EGFR, CDK6, MDM2, CDK4, and TNFSF13B) were tested in an independent set of 111 primary GBMs by using FISH and immunohistological assays. Paper-12256696.
CDK4 and CDK6, which are activated by D-type cyclins during the G(1) phase of the cell cycle, are thought to be responsible for phosphorylation of the retinoblastoma gene product (pRb). Paper-8662454.
The amino-acid residues of p16 important for its interaction with cdk4 and cdk6 and for the inhibition of pRb phosphorylation were defined by an alanine substitution series of peptides. Paper-726606.
When we examined the effects of this drug on ACHN cells, trichostatin decreased the levels of CDK4, CDK6, cyclin D1 and cyclin A proteins. p27 protein was increased by trichostatin. Paper-9768567.
Microarray CGH revealed frequent gains of EGFR, DAB2, MSH2, KCNK12, DDX15, CDK6, and LAMA3, and losses of CDH1, GLTSCR2, EGR1, CTSB, GATA3, and SULT2A1. Paper-11350956.
The D-type cyclins and their major kinase partners CDK4 and CDK6 regulate G0-G1-S progression by contributing to the phosphorylation and inactivation of the retinoblastoma gene product, pRB. Paper-1767478.
CDKN2A (also known as P16, INK4, p16INK4A and MTS1) is allelic to this locus and encodes a cdk4/ cdk6 kinase inhibitor that constrains cells from progressing through the G1 restriction point. Paper-1713943.
The concomitant high expression of the oncogenic protein CDK4 (and of CDK6), we observed, may amplify the leukemic advantage of prolonged lifespan blast cells by favoring cell progression through G1 phase. Paper-1741911.
By CD40 signalings, both Cdk4 and Cdk6 resume their normal expression levels, which are sufficient for passing the restriction point in G1 even in the presence of the apoptotic signals mediated by sIgM. Paper-432598.
On the other hand, there was no significant difference in expression of proteins such as Rb, p16, cdk4, cdk6, cyclin A and cyclin D1 between the normal and immortalized human fibroblasts. Paper-828445.
Overexpression of cyclin D1, the regulatory subunit of cyclin-dependent kinases ( cdk4 and cdk6) involved in cell cycle control, has often been found in breast cancer and other types of human cancer. Paper-9731599.
In contrast, Cdk4 was expressed at high levels in several tumor cell lines and Cdk6 was ectopically expressed in two sarcoma lines, suggesting a possible involvement of these two Cdks in oncogenesis. Paper-129183.
Molecular analysis did not detect any EVI1/ CDK6 chimeric transcript generated by t(3;7)(q26;q21), but did indicate overexpression of EVI1, which occurs frequently in progression to myeloid BC in CML. Paper-10857387.
Overexpression of its product, p16, has been shown to block the transition through the G1/ S phase of the cell cycle in a pRb-dependent fashion by inhibiting the cyclin D-dependent kinases cdk4 and cdk6. Paper-726606.
Multiple shRNAs against CDK6, MET, and MAP2K1 (also known as MEK1) preferentially inhibited the viability of 786-O and RCC4 VHL-/- cells compared with their wild-type pVHL-reconstituted counterparts. Paper-13060380.
Western blots also revealed that the G1-specific cell cycle regulators, CDK2, CDK4, CDK6, cyclin D1, and cyclin E, had been significantly (>60%) down-regulated in IFN/ PDF-treated cells. Paper-13543729.
Lineage specific composition of cyclin D- CDK4/ CDK6- p27 complexes reveals distinct functions of CDK4, CDK6 and individual D-type cyclins in differentiating cells of embryonic origin. Paper-14343177.
In the sixth tumor, which carried amplified sequences of Met but not of Cdk6, coexpression of Met and the normally silent hepatocyte growth factor gene ( Hgf; the ligand of Met) was observed. Paper-9097472.
A progression signal such as that delivered by interleukin-2 then induces a second phase of Cdk6, Cdk4, and Cdk2 activation, along with sustained phosphorylation of p110Rb in the activated T cells. Paper-397627.
Based on a mRNA overexpression criterion, 11 genes were selected: ELF3 and SLC45A3 on 1q; CLDN12, CDK6, SMURF1, ARPC1B, ZKSCAN1, MCM7, and COPS6 on 7q; and FDFT1 and CTSB on 8p. Paper-13589189.
No gene rearrangement or deletion was observed in the p19INK4d gene in these cell lines; however, expression of CDK4 and CDK6 was elevated relative to matched normal brain tissue in eight of 18 GBM tumours (44%). Paper-8397413.
The SK29-MEL-1 cell line harboring an R24C mutation in Cdk4 expressed wild-type pRb and overabundant p16, the latter preventing endogenous Cdk6 but not Cdk4 from associating with cyclin D1. Paper-827203.
These results suggest a mechanism for coupling proliferation and the block to differentiation in these leukemic cells through the action of an oncogenic transcription factor ( PU.1) on a key cell cycle regulator ( CDK6). Paper-9757807.
D-cyclin-cdk activity is required for Rb phosphorylation in v-Jun-transformed cells, since ectopic expression of the cdk4- and cdk6-specific inhibitor p16(INK4A) inhibits both DNA synthesis and cell proliferation. Paper-2149144.
This may have important physiological consequences in that the kinase activity triggered by this viral cyclin may abrogate cell cycle checkpoints in addition to those targeted by cellular cyclin D- cdk6 kinase. Paper-1014651.
These results indicate that Cdk6 is a critical regulator of BMP-2-induced osteoblast differentiation and that its Smads-mediated down-regulation is essential for efficient osteoblast differentiation. Paper-10344140.
In non-tumorigenic mouse liver cells cyclin D1 associated with CDK6, CDK4 or CDK2 to form binary ( cyclin D1-CDK), tertiary ( cyclin D1-CDK-p27KIP1) or quaternary ( cyclin D1-CDK-p21WAF1- PCNA) complexes. Paper-1493351.
Cdk6 up-regulation in TDP-43-depleted cells is accompanied by an increase in phosphorylation of two of its major targets, the retinoblastoma protein pRb and pRb-related protein pRb2/p130. Paper-14293770.
A recent meta-analysis of genome-wide association studies identified 6 genetic regions for susceptibility to autoantibody-positive RA: CD40, KIF5A/ PIP4K2C, CDK6, CCL21, PRKCQ, and MMEL1/TNFRSF14. Paper-13922212.
Since Runx transcription factors play central roles in hematopoietic, neuronal and osteogenic lineages, this novel, noncanonical Cdk6 function may control terminal differentiation in multiple tissues and cell types. Paper-13219214.
Of the G(1) cell cycle factors examined, the expression of cyclin-dependent kinase 6 ( Cdk6) was found to be strongly down-regulated by BMP-2/Smads signaling, mainly via transcriptional repression. Paper-10344140.
Thus, the CCND1- CDK6 complex is like to negatively regulate Wnt signaling by mediating beta-catenin phosphorylation and its subsequent degradation in Wnt-stimulated cells. Paper-12441209.
The structures of Cdk6 bound to p16INK4a and to the related p19INK4d reveal that the INK4 inhibitors bind next to the ATP-binding site of the catalytic cleft, opposite where the activating cyclin subunit binds. Paper-1578317.
Coexpression of p16 partially protected cells from cell death. p16 and KSHV-cyclin can form a ternary complex with CDK6 that can be detected by binding assays as well as by conformational changes in CDK6. Paper-9145950.
Here, we show that the representative members of both families of CDK inhibitors, p21waf1,cip1, p27kip1, and p18, can prevent the phosphorylation of their CDK partners, CDK2 and CDK6, by CDK-activating kinase. Paper-308575.
RESULTS: We have identified a 20-residue synthetic peptide--corresponding to amino acids 84-103 of p16--that interacts with cdk4 and cdk6, and inhibits the in vitro phosphorylation of pRb mediated by cdk4-cyclin D1. Paper-726606.
While p15INK4B and its binding to both cdk4 and cdk6 increased with increasing passage, some cyclin D1- bound cdk4 and cdk6 persisted in senescent cells, whose inhibition could not be attributed to p15INK4B. Paper-8645884.
The D-cyclin-associated kinases, cyclin-dependent kinase ( cdk) 4 and cdk6, are important regulators of the G(1)-S phase transition and are elevated in several types of cancers, including gliomas. Paper-9917481.
We now use an in vitro kinase assay, phosphopeptide-specific antiserum, and the cdk inhibitor roscovitine to demonstrate that S48 and S424 are also phosphorylated by cdk1 or cdk6 in hematopoietic cells. Paper-14333299.
The present study indicates that, in human prostate cancer cells, CDK6 can also bind to the androgen receptor ( AR) and stimulate its transcriptional activity in the presence of dihydrotestosterone. Paper-10784041.
Induced by growth factor stimulation, D-type cyclins assemble with cyclin-dependent kinases CDK4 and CDK6 to form holoenzymes that facilitate exit from G1 by phosphorylating key substrates, including the retinoblastoma protein. Paper-289153.
Mammalian cells require a cyclin D-dependent kinase for the cell cycle start, yet many mesenchymal cells express three seemingly redundant D cyclins and similarly, seemingly redundant Cdk4 and Cdk6 as their kinase partners. Paper-8838635.
Taken together, our data suggest that the effects of miR-34a on G1 cell cycle arrest are through the down-regulation of CCND1 and CDK6, which is associated with other targets of miR-34a either additively or synergistically. Paper-14309110.
By use of a yeast interaction screen to search for CDK6-interacting proteins, we have also identified an 18-kD human protein, p18, that is a homolog of the cyclin D- CDK4 inhibitors p16 (INK4A/MTS1) and p14 ( MTS2/ INK4B). Paper-144006.
Seventy-nine tag SNPs were used to evaluate 240 common SNPs found in the genes: CCND1, CCND2, CCND3, CCNE1, CDK2, CDK4, CDK6, CDKN1A, CDKNIB, CDKN2A/ CDKN2B, CDKN2C and CDKN2D. Paper-14288406.
Viral cyclin- cdk6 complexes share this capacity with cyclin A- cdk2, demonstrating that in addition to functioning as G(1)-phase cyclin-cdk complexes, they function as S-phase cyclin-cdk complexes. Paper-8689567.
Here, we found that Tax binds to a cyclin-dependent kinase inhibitor, p16Ink4a. p16Ink4a binds to cyclin-dependent kinases, CDK4 and CDK6, and inhibits their activity, resulting in suppression of G1 phase progression. Paper-1088900.
The protein expression of CDK6, CDK2, p21CIP1, p27KIP1 and phosphorylated RB (S807/S811) was evaluated using protein arrays as a novel and highly sensitive platform for profiling of protein abundance and protein phosphorylation. Paper-12827200.
Specific binding of the p16 product to the cyclin-dependent protein kinases cdk4 or cdk6 inhibits the catalytic activity of the cyclin D-cdk complex, and consequently arrests the cell cycle at the G1/ G2 phase. Paper-12339789.
The passage of mammalian cells through the restriction point into the S phase of the cell cycle is regulated by the activities of Cdk4 and Cdk6 complexed with the D-type cyclins and by cyclin E/ Cdk2. Paper-1217408.
We detected no CDK6 mutations within the p16 ( CDKN2A) binding domain in index cases from 60 melanoma-prone kindreds that lacked germline mutations in the coding regions of either CDKN2A or within the entire CDK4 coding region. Paper-8498044.
We demonstrate that transforming growth factor-alpha (TGFalpha) induces cyclin D1 mRNA in esophageal squamous epithelial cells, and this appears to correlate with increased cyclin D1 protein expression and cyclin-dependent kinase 6 activity. Paper-1277344.
Phosphorylation of pRb by cyclin-dependent kinase 6/4-cyclin D and of p130 did not occur and c-Myc, cyclin D3, and p107 were not induced, consistent with cell cycle inhibition early during the transition from G(0) to G(1). Paper-9090319.
Although complexes involving cdk4 or cdk6 were readily observed in many of the cell lines, no complexes were detectable in human cells harbouring DNA tumour virus oncoproteins or in which the retinblastoma gene product (pRb) is mutated or missing. Paper-120238.
Epigenetic down-regulation of miR-124a induced an up-regulation of its target, CDK6, and phosphorylation of retinoblastoma ( Rb) and contributed to the abnormal proliferation of ALL cells both in vitro and in vivo. Paper-13774373.
The substrate specificity, the expression pattern of this kinase, and the ability to deplete 50% of this kinase activity with a CDK6-specific antibody suggest that the CDK6 protein mediates, in part, the p27-associated Rb-kinase activity. Paper-918005.
METHODS: Sixteen cancer-associated p16 mutant proteins, resulting from missense mutations, were characterized for their ability to bind and inhibit the cyclin-dependent kinases ( CDK4 and CDK6) and to induce cell cycle arrest in G(1) phase. Paper-2000990.
The positive phenotypes identified were as follows: Rb, 39.1%; E2F1, 69.6%; cyclin D1, 30.4%; CDK4, 100%; CDK6, 30.4%; 39.1%; p27(KIP1), 47.8%; p21(WAF1/ CIP1), 39.1%; p53, 43.5%; Mdm2, 17.4%; Bcl-2, 91.3%; and Bax, 100%. Paper-12021570.
Inactivation of the tumor-suppressor gene p16(INK4a/ CDKN2), a specific inhibitor of the cyclin-dependent kinases CDK4 and CDK6, is the most common genetic alteration in human pancreatic cancer, making it an ideal target for gene replacement. Paper-8862847.
In cells, expression of CDK6 or to a lesser degree of a nonphosphorylatable CDK6(T177A) together with KSHV-cyclin induced apoptosis, indicating that CDK6 activation by KSHV-cyclin can proceed in the absence of phosphorylation by CAK in vivo. Paper-9145950.
Assays using model reporter constructs as well as endogenous target genes showed that the activity of c-Myb was inhibited by cyclin D1 plus CDK4 or CDK6 but stimulated by expression of the CDK inhibitors p16 Ink4a, p21 Cip1, or p27 Kip1. Paper-10733463.
In the glioblastomas with no alterations of CDKN2A, CDK4 or RB1, several other genes ( CCND1, CCND2, CCND3, CDK6, E2F, CDK7, MYC and MYCN) whose products take part in cell cycle regulation were examined. Paper-696237.
Most commonly, such mutations involve CDKN2A, a cyclin-dependent kinase inhibitor of two kinases, CDK4 and CDK6, which phosphorylate the retinoblastoma protein (pRB) and thereby promote passage through the G1/S cell-cycle restriction point. Paper-8498044.
We here show that cyclin-dependent kinase 6 ( Cdk6) is specifically expressed in proliferating hematopoietic progenitor cells, and that Cdk6 inhibits transcriptional activation by Runx1, but not C/EBPalpha or PU. Paper-13219214.
Among the genes analyzed, those most often targeted by amplification were SDC1 and CYP1B1 in 2p21 approximately p25 and CDK6 and MET in 7q21 approximately q31, but all of the 15 genes tested were found to be amplified in at least two tumors. Paper-12734254.
Here we show that CDK4 and CDK6 can extend the life span of HDFs that have inactivating mutations in both alleles of INK4a or in which INK4a levels are repressed, indicating that overexpression of CDK4/6 is not equivalent to ablation of p16(INK4a). Paper-13260835.
The p16INK4 family of CDK inhibitors specifically prevent the phosphorylation of the retinoblastoma susceptibility gene product, pRb, by inhibiting the kinase activity of CDK4 and CDK6, thereby keeping pRb in its active form as a growth suppressor. Paper-794748.
The four members of the INK4 gene family, p16(INK4a), p15(INK4b), p18(INK4c) and p19(INK4d), are known to bind to and inhibit the closely related cyclin-dependent kinases CDK4 and CDK6 as part of the regulation of the G1/S transition in the cell division cycle. Paper-1602091.
Early onset of G1 cell cycle arrest along with upregulation of the cyclin dependent kinase inhibitor p27Kip1 and downregulation of Cdk2, Cdk4, Cdk6, and Cyclin E has also been observed in Jak3-overexpressing 32Dcl3 cells. Paper-10800862.
Statistical analysis using configural frequency analysis and regression analysis revealed that cyclin D2 and CDK4 expression were strongly correlated (r(2) = 0.682; P = 0.000052), whereas expression of CDK6 did not correlate with either of them (r(2) = 0.382; P = 0.00085). Paper-8840207.
Here we report that E2F1 directly transactivates miR-449a/b. miR-449a/b targets and inhibits oncogenic CDK6 and CDC25A, resulting in pRb dephosphorylation and cell cycle arrest at G1 phase, revealing a negative feedback regulation of the pRb- E2F1 pathway. Paper-14053452.
For four complexes, LIR-1/HLA-A2, Actin/ DNase I, CDK2/ cyclin, and CDK6/p16(INK4a), the motions calculated for the monomer exhibiting the largest conformational change, in its unbound (free) form, correlate with the experimentally observed structural changes upon binding. Paper-11175673.
To determine a possible mechanism by which senescent human fibroblasts maintain a hypophosphorylated Rb, we examined the expression levels and interaction of the Rb kinases, CDK4 and CDK6, and the cyclin-dependent kinase inhibitors p21 and p16 in senescent HDFs. Paper-811959.
Here we report the chromosomal mapping of two cdks, cdk3 and cdk6, two putative cdks, PISSLRE and PITALRE, and one cyclin-dependent kinase inhibitor, p27, to chromosomal regions which may be altered in human tumors and examine their possible involvement in some of these malignancies. Paper-177874.
However, neither BMP-2 treatment nor Cdk6 overexpression significantly affected cell proliferation, suggesting that the inhibitory effect of Cdk6 on cell differentiation was exerted by a mechanism that is largely independent of its cell cycle regulation. Paper-10344140.
Cyclins D1, D2 and D3 preferentially associate with two closely related members of the cyclin-dependent kinase family, Cdk4 and Cdk6 and the various complexes are each capable of phosphorylating the retinoblastoma gene product ( pRb), at least in vitro. Paper-178932.
Here we show that CD28 costimulation directly regulates T cell cycle entry and progression through the G1 phase in an IL-2-independent manner resulting in activation of cyclin D2- associated cdk4/ cdk6 and cyclin E- associated cdk2. Paper-2061557.
CONCLUSIONS: These results demonstrate that a p16-derived peptide can mediate three of the known functions of p16: firstly, it interacts with cdk4 and cdk6; secondly, it inhibits pRb phosphorylation in vitro and in vivo; and thirdly, it blocks entry into S phase. Paper-726606.
OBJECTIVE: The recently cloned gene p16 ( MST1) has been identified as a putative tumor suppressor gene that binds to CDK4 and CDK6 (cyclin-dependent kinases), preventing their interaction with cyclin D1 and thereby preventing cell cycle progression at the G1 stage. Paper-1068141.
Sixty primary GISTs previously characterized for 9p loss by comparative genomic hybridization were analysed for mRNA expression of p16INK4A, p15INK4B, CDK4, CDK6, cyclin D, p21CIP1p27KIP1, CDK2, cyclin E, cyclin B, RB and E2F1, using quantitative RT-PCR. Paper-12827200.
Our results point to some particularities of cell cycle regulation in two lymphoma sub-types: 1) a low expression of cyclin D3 and cdk6 in mantle cell lymphomas and 2) a discrepancy between the high proliferative activity and the level of protein expression in Burkitt's lymphomas. Paper-2025983.
CONCLUSIONS: Although many critical interactions between cyclin A and CDK2 would be conserved in a v-cyclin-CDK2 complex, some appear sterically or electrostatically unfavorable due to shifts in the backbone conformation or sidechain differences and may contribute to v-cyclin selectivity for CDK6. Paper-8323611.
Molecular definition of the amplicon indicated that PEG10 ( paternally expressed gene 10), a paternally expressed imprinted gene, was amplified together with CDK14 ( cyclin-dependent kinase 14; previously PFTAIRE protein kinase 1, PFTK1) and CDK6 ( cyclin-dependent kinase 6). Paper-14694899.
In summary, our data demonstrate (i) that individual cyclin D isoforms are utilized in cells lineage specifically, (ii) that fundamental difference in the function of CDK4 and CDK6 exists, and (iii) that cyclin D- CDK4/6 complexes function in the cytoplasm of differentiated cells. Paper-14343177.
Immunohistochemical stains were carried out on tissue microarrays to evaluate the expression of proteins involved in the G(1)-S transition and proteins that regulate apoptosis including Rb, E2F1, cyclin D1, CDK4, CDK6, p27(KIP1), p21(WAF1/ CIP1), p53, Mdm2, Bcl-2, and Bax. Paper-12021570.
The I3C-mediated cell cycle arrest and repression of CDK6 production were also observed in estrogen receptor-deficient MDA-MB-231 human breast cancer cells, which demonstrates that this indole can suppress the growth of mammary tumor cells independent of estrogen receptor signaling. Paper-1344465.
Substitution of two valine residues corresponding to amino acids 95 and 96 (V95A and V96A) of the p16 peptide reduces the binding to cdk4 and cdk6 and increases its IC0.5 for kinase inhibition approximately threefold when linked to the Antennapedia homeodomain carrier sequence. Paper-1328674.
22 single nucleotide polymorphisms ( SNPs) within or in the vicinity of CCL21, CD40, CDK6, IL21, IL2RB, IRF5, KIF5A, KLF12, MMEL1, PRKCQ, STAT4, TNFAIP3, and TRAF1/ C5 have been genotyped in >600 German WG cases and >800 matched controls. Paper-14677970.
RNA expression analysis of 11 adenocarcinomas by reverse-transcription polymerase chain reaction was performed for cancer-related genes residing at 7q21 ( ABCB1, ABCB4, CDK6, HGF, DMTF1, SRI, TP53AP1) and 20q13 ( ZNF217, BCAS1, CYP24, TNFRSF6B). Paper-11815652.
p16(INK4a), a tumor suppressor gene that inhibits cyclin-dependent kinase 4 and cyclin-dependent kinase 6, is also implicated in the mechanisms underlying replicative senescence, because its RNA and protein accumulate as cells approach their finite number of population doublings in tissue culture. Paper-8891868.
The amount of CDK4 and CDK6 associated with p27 does not change in a cell cycle-dependent fashion; in contrast, the amount of CDK2 associated with p27 is lowest in early G1 cells and increases to a maximum in mid-G1 phase, reaching a steady-state level in late G1-phase cells. Paper-918005.
The reintroduction of miR-148a and miR-34b/c in cancer cells with epigenetic inactivation inhibited their motility, reduced tumor growth, and inhibited metastasis formation in xenograft models, with an associated down-regulation of the miRNA oncogenic target genes, such as C-MYC, E2F3, CDK6, and TGIF2. Paper-12931043.
Therefore, the present study determined expression of the cell cycle regulators, cyclin D1 and cyclin E, and their cyclin-dependent kinases, Cdk2, Cdk4, and Cdk6, and Ki67 a marker of cell proliferation within the baboon fetal adrenal cortex during advancing stages of gestation. Paper-12397233.
EGCG caused growth arrest at G1 stage of cell cycle through regulation of cyclin D1, cdk4, cdk6, p21/ WAF1/ CIP1 and p27/ KIP1, and induced apoptosis through generation of reactive oxygen species and activation of caspase-3 and caspase-9. Paper-13292099.
This strategy allowed us to identify seven low-penetrance genes, six of them ( STAT1, AURKA, BCL2, CDKN2B, CDK6, and COMT) consistently associated with sMTC risk in the two case-control series and a seventh (HRAS) with individual SNPs and haplotypes associated with sMTC in the Spanish data set. Paper-12513224.
Five genes were found to be upregulated only in tumours, RBL2, E2F2, CDK6, CCNE1 and MYC; eight in tumours and HSILs, E2F1, E2F3, E2F5, CCND1, CDK2, CDKN1B, PCNA and POLA, and five in tumours, HSILs and LSILs, TP53, E2F4, CDKN1A, CDKN2A and DHFR. Paper-13009989.
However, recent experiments in which the genes encoding all three D-type cyclins, the two E-type cyclins, cyclin D-dependent Cdk4 and Cdk6, or cyclin E-dependent Cdk2 have been disrupted in the mouse germ line have revealed that much of fetal development occurs normally in their absence. Paper-10649699.
While most polymorphisms did not show suspicious effects on WG susceptibility, SNPs representing TNFAIP3 (rs6922466, p = 0.032, odds ratio (OR) 0.83, 95% confidence interval (CI) 0.7--0.98) and CDK6 (rs42041, p = 0.0201, OR 1.21, 95% CI 1.03-1.43) revealed nominally significant differences in allele distribution. Paper-14677970.
Since exit from the cell cycle is a necessary step in terminal differentiation, down-regulation of a mitogenic factor may be expected in this process, however it is surprising that this association has not been previously uncovered and that it is apparently not shared with cdk4, long understood to be a functional homolog of cdk6. Paper-11313650.
As the genes encoding the CDK4- and CDK6-inhibitors ( CDK4/6-inhibitors) p16INK4A/ CDKN2/ MTS1 and p15INK4B/ MTS2 have been found to be altered in many cancer cell lines and primary neoplastic tissues, CDK-inhibitors in general and CDK4/6-inhibitors in particular are now a se: of candidate tumor suppressors. Paper-944243.
Moreover, co-immunoprecipitation assays using Wnt3a-conditioned medium reveals that while Wnt stimulation leads to the dissociation of beta-catenin from axin and casein kinase Ialpha (CKIalpha), Wnt treatment promotes an increase in CCND1 level and the association of beta-catenin with CCND1- CDK6. Paper-12441209.
We have previously shown that a 20 amino acid peptide derived from the third ankyrin-like repeat of the p16CDKN2/ INK4a (p16) tumour suppressor protein (residues 84-103 of the human p16 protein) can bind to cdk4 and cdk6 and inhibit cdk4-cyclin D1 kinase activity in vitro as well as block cell cycle progression through G1. Paper-1328674.
RESULTS: The TT and CC/ CG genotypes of 2 single-nucleotide polymorphisms, rs4810485 ( CD40) and rs42041 ( CDK6), respectively, were associated with a higher rate of joint destruction in ACPA-positive RA patients (P=0.003 and P=0.012, respectively), with rs4810485 being significant after Bonferroni correction for multiple testing. Paper-13922212.
Since many hematopoietic cells employ predominantly Cdk6 for the cell cycle start and perform anchorage-independent growth by nature, this finding raises the possibility that the mechanism by which oncogenic stimulation invokes anchorage-independent growth of NRK cells is similar to the one used for hematopoietic cell proliferation. Paper-8973107.
We have used a single nucleotide polymorphism (SNP)-tagging approach to evaluate common variants in 13 genes involved in cell cycle control- CCND1, CCND2, CCND3, CCNE1, CDK2, CDK4, CDK6, CDKN1A, CDKN1B, CDKN2A, CDKN2B, CDKN2C, and CDKN2D-and risk of invasive epithelial ovarian cancer. Paper-13168546.
Thus, v-cyclin resembles cellular type D cyclins in primary sequence, in its association with cdk6, by its ability to activate protein kinase activity, and by the presence of functional cyclin box sequences. v-Cyclin exhibited a selective preference for association with cdk6 over other cyclin-dependent kinases and a high level of kinase activation. Paper-135952.
Cell cycle analysis showed reduced cyclin D1 and CDK6 and increased phospho- Cdc-2 (Tyr15) and p15INK4B in erbB2-inhibited cells, suggesting that nonfunctional EGFR/erbB2 complexes exert their inhibitory effects at various stages of the cell cycle to block the progression of cells through G2/M via Akt/ GSK-3/ Cdc2 pathway. Paper-12544263.
Biochip analysis showed that SWCNTs can induce up-regulation expression of cell cycle-associated genes such as p16, bax, p57, hrk, cdc42 and cdc37, down-regulation expression of cell cycle genes such as cdk2, cdk4, cdk6 and cyclin D3, and down-regulation expression of signal transduction-associated genes such as mad2, jak1, ttk, pcdha9 and erk. Paper-11297046.
These synonyms are used for gene CDK6 (cyclin-dependent kinase 6): Serine/threonine-protein kinase PLSTIRE, PLSTIRE, MGC59692, Cell division protein kinase 6.
These accession numbers are used for gene CDK6: AK172791 (NCBI_GENBANK__AC), AK123134 (NCBI_GENBANK__AC), A4D1G0 (UNIPROT__AC).
CDK6 is a homologue of si:ch211-234f14.1 (si:ch211-234f14.1) from Danio rerio.
CDK6 is a homologue of CDK6 (cyclin-dependent kinase 6) from Bos taurus.
CDK6 is a homologue of CDK6 (cyclin-dependent kinase 6) from Pan troglodytes.
CDK6 is a homologue of CDK6 (cyclin-dependent kinase 6) from Gallus gallus.
CDK6 is a homologue of CDK6 (cyclin-dependent kinase 6) from Canis lupus familiaris.
CDK6 is a homologue of Cdk6 (cyclin-dependent kinase 6) from Mus musculus.
CDK6 is a homologue of Cdk6 (cyclin-dependent kinase 6) from Rattus norvegicus.
CDK6 is a homologue of cdk-4 (Cyclin-Dependent Kinase family) from Caenorhabditis elegans.
CDK6 is a homologue of Cdk4 (Cyclin-dependent kinase 4) from Drosophila melanogaster.
CDK6 is a homologue of AgaP_AGAP005817 (AGAP005817-PA) from Anopheles gambiae str. PEST.
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