The most recent information on CDK6 is here. Click here for the function of CDK6. Edit this page in Wiki Genes - CDK6 or see Wiki Gene. CAK-independent activation of CDK6 by a viral cyclin. Paper-9145950. The increased p27Kip1 bound preferentially to CDK6. Paper-995380. Identification of G1 kinase activity for cdk6, a novel cyclin D partner. Paper-113104. Recombinant p18 inhibits the kinase activity of cyclin D- CDK6. Paper-144006. 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. 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. Nucleophosmin phosphorylation by v-cyclin- CDK6 controls KSHV latency. Paper-14681086. Cyclin-dependent kinase ( cdk6) and p16 in pancreatic endocrine neoplasms. Paper-10603421. Modulation of beta-catenin by cyclin-dependent kinase 6 in Wnt-stimulated cells. Paper-12441209. Isolation and characterization of p19INK4d, a p16-related inhibitor specific to CDK6 and CDK4. Paper-679463. Caspases 3 and 8 were strongly activated while the amount of CDK6 was reduced by TNF-alpha. Paper-10559179. The dephosphorylation of Cdk2 and Cdk6 by PP2C isoforms was inhibited by the binding of cyclins. Paper-8606392. Functional availability of gamma-herpesvirus K-cyclin is regulated by cellular CDK6 and p16INK4a. Paper-15245385. CDK4 and CDK6 delay senescence by kinase-dependent and p16INK4a-independent mechanisms. Paper-13260835. We find that KSHV-cyclin can activate CDK6 independent of phosphorylation by CAK in vitro. Paper-9145950. Thus, p16 mutant proteins that retain CDK4 and CDK6 binding may have more subtle functional defects. Paper-2000990. A combined model of both CDK6 and CDK4 expressions is a superior predictor of survival than either alone. Paper-16061787. 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. The control of Cdk6 expression mediated by TDP-43 involves GT repeats in the target gene sequence. Paper-14293770. A CDKN2A mutation in familial melanoma that abrogates binding of p16INK4a to CDK4 but not CDK6. Paper-12513207. Cdk6- cyclin D3 complex evades inhibition by inhibitor proteins and uniquely controls cell's proliferation competence. Paper-8838635. Our data suggest that the balance between CDK6 and p16INK4a regulates the availability of functional K-cyclin in human cells. Paper-15245385. Cdk6 blocks myeloid differentiation by interfering with Runx1 DNA binding and Runx1-C/EBPalpha interaction. Paper-13219214. Cyclin D1 and its kinase partners CDK4 and CDK6 play an important role in regulating the G1-S phase of the cell cycle. Paper-15443204. A low-level amplification (10%) was observed at the 12q13 region containing the CDK6 homologue cyclin-dependent kinase 4 ( CDK4). Paper-16061787. Interestingly, CDK6 kinase activity was dramatically elevated due to high levels of cyclin D3 in association with CDK6. Paper-1493351. Growth suppression by p18, a p16INK4/MTS1- and p14INK4B/ MTS2-related CDK6 inhibitor, correlates with wild-type pRb function. Paper-144006. Removal of TDP-43 in human cells significantly increases cyclin-dependent kinase 6 ( Cdk6) protein and transcript levels. Paper-14293770. Immunohistochemistry revealed strong expression of PPM1D in 148 (88%) of 168 and CDK6 in 50 (30%) of 169 medulloblastomas. Paper-11164350. The homologous cyclin-dependent kinases (CDK) CDK4 and CDK6 integrate mitogenic and oncogenic signaling cascades with the cell cycle. Paper-13886819. We have isolated cDNA sequences corresponding to the MTS2 genomic fragment that encodes the CDK4- and CDK6-associated p14 protein. Paper-144006. Toll-like Receptor-4 ( TLR4) Down-regulates MicroRNA-107, Increasing Macrophage Adhesion via Cyclin-dependent Kinase 6. Paper-16088278. 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. Parkin enhances the expression of cyclin-dependent kinase 6 and negatively regulates the proliferation of breast cancer cells. Paper-15397887. Specific knockdown of CDK4 and/or CDK6 by siRNAs shows that they are required for proliferation of EAC cells and that their function is additive. Paper-16061787. Activation of the cyclin D2 and cdk6 genes through NF-kappaB is critical for cell-cycle progression induced by HTLV-I Tax. Paper-13076259. Rodent fibroblasts engineered to overexpress both Cdk6 and cyclin D3 highly resist serum starvation- or cell-cell contact-imposed G(1)-arrest. Paper-8838635. 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. TDP-43 regulates retinoblastoma protein phosphorylation through the repression of cyclin-dependent kinase 6 expression. Paper-14293770. The D-type cyclin-dependent kinases CDK4 and CDK6 are complexed with many small cellular proteins (p14, p15, p16, p18, and p20). Paper-144006. Furthermore, increased protein-levels of PPM1D and CDK6 may link the TP53 and RB1 tumor suppressor pathways to medulloblastoma pathomechanisms. Paper-11164350. 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. Short-hairpin RNA (shRNA)-mediated inhibition of cyclin D2 and CDK6 induction suppressed Tax-induced activation of E2F in T cells. Paper-13076259. Tax stimulates the cell cycle in the G(1) phase by activating the cyclin-dependent kinase ( CDK) CDK4 and CDK6 holoenzyme complexes. Paper-9441141. 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. These observations suggest that CDK4 and CDK6 are not functionally redundant and underscore the importance of CDK4 in the development of melanoma. Paper-12513207. 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. Based on both in vitro and in vivo analyses, the R24P variant is specifically defective for binding to CDK4 but remains able to associate with CDK6. Paper-12513207. 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. Furthermore, silencing of p16INK4a promoted K-cyclin- CDK6 complex formation and hence induced K-cyclin-associated kinase activity in HEK293 cells. Paper-15245385. 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. 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. An immunoprofile of HGF, CDK6 and MET revealed a strong correlation between aCGH and immunohistochemical protein expression for CDK6 ( P = 0.002). Paper-12821658. Here, we examined whether overexpression of cyclin D1, CDK4 and CDK6 can deregulate the link between oral keratinocyte proliferation and differentiation. Paper-15443204. 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. Normal progression through G1 is promoted by the activity of the cyclin-dependent protein kinases CDK4 and CDK6 (ref. 2), which are inhibited by the protein p16INK4. Paper-131172. 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. We have found that the putative miR-107 target cyclin-dependent kinase 6 ( CDK6) expression is increased by TLR4 as a result of the decrease in miR-107. Paper-16088278. 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. The expression of cyclin D1 ( CCND1), CCNE2, CCN-dependent kinase 6 ( CDK6), and CDK2 was restored, whereas that of CCNA, CCNB1, and CDK1 was irreversibly attenuated. Paper-13785430. 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. Here, c-Myb was identified as part of a protein complex from human T cells containing the cyclin-dependent kinase ( CDK) CDK6. Paper-10733463. 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. CONCLUSIONS: We suggest that CDK6 is the driver of 7q21 amplification and that both CDK4 and CDK6 are prognostic markers and bona fide oncogenes in EAC. Paper-16061787. 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. 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. 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. 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. 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. 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. 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. 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. Here we demonstrate that cyclin-dependent kinase 6 ( CDK6), in association with cyclin D1 ( CCND1), directly binds to beta-catenin. Paper-12441209. 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. Expression of cyclin D2 and CDK6 activated the transcription factor E2F, which is essential for cell-cycle progression, in both T cells and fibroblasts. Paper-13076259. 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. 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. Cdk6- mediated inhibition of granulocytic differentiation could be reversed by excess Runx1, consistent with Runx1 being the major target for Cdk6. Paper-13219214. 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. 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. 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. In contrast to p21 and p27 whose interaction with CDK subunits is dependent on or stimulated by the cyclin subunit, the interaction of p19 and p18 with CDK6 is hindered by the cyclin protein. Paper-679463. 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. 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. 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. 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. Tax activated cyclin D2 and cdk6 promoters in T cells, but not in fibroblasts, depending on its ability to activate the transcription factor nuclear factor (NF)-kappaB. Paper-13076259. 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 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. 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. 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. 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. 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. 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. 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. Finally, shRNA-mediated downregulation of NF-kappaB p65 or p100 expression reduced Tax-induced activation of cyclin D2 and/or cdk6 promoters and cell-cycle progression in T cells. Paper-13076259. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. The trans-activator protein Tax of HTLV-I can promote cell-cycle progression in resting T cells along with induction of cyclin D2 and cyclin-dependent kinase ( cdk6) gene expression. Paper-13076259. 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. Conversely, p15(INK4b)-independent transforming growth factor beta-mediated G1 arrest of hepatocellular carcinoma cells results in loss of Cdk2 kinase activity with continued Cdk6 kinase activity and pRb remains only hypo-phosphorylated. Paper-1200274. METHODS: A total of 4 SNPs (rs4810485 in CD40, rs2812378 in CCL21, rs42041 in CDK6 and rs6682654 in CD244) were genotyped in a UK cohort comprising 3962 UK patients with RA and 3531 healthy controls using the Sequenom iPlex platform. Paper-14115353. 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. Our study demonstrates that the KSHV v-cyclin and cellular CDK6 kinase phosphorylate NPM on threonine 199 (Thr199) in de novo and naturally KSHV-infected cells and that NPM is phosphorylated to the same site in primary KS tumors. Paper-14681086. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. These results indicate that Tax-induced cell-cycle progression in T cells is mediated, at least in part, through cell-type-specific activation of the cyclin D2 and cdk6 genes through NF-kappaB and may be important for the cell-type-specific oncogenesis. Paper-13076259. Breast epithelial cells exogenously overexpressed with erbB2 decreased the expression of miR-205, whereas increased the expression of cyclin D1, cyclin E, cyclin-dependent kinase 2 ( CDK2), cyclin-dependent kinase 4 ( CDK4), and cyclin-dependent kinase 6 ( CDK6). Paper-16148799. 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. 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. 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. 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. The mechanism involves inhibition of cyclin D3:cdk4/ cdk6 activity and increased protein phosphatase-2A ( PP2A) activity in liver nuclei, which stabilizes the dephosphorylated form of the transcription factor C/EBPalpha preventing the age-dependent formation of the C/EBPalpha-Rb-E2F4-Brm nuclear complex. Paper-12629000. 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. Binary cyclin D1-p18/ p19 or cyclin D1- CDK6 complexes are highly stable and cannot be dissociated by excess amounts of cyclin D1 or p19/ p18 proteins, suggesting that p16 inhibitors and D cyclins may interact with CDKs 4 and 6 in a competing or potentially mutually exclusive manner. Paper-679463. 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. 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. 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. However, we did not observe significant changes in the levels of the G1-associated cyclin D1 and E. On the other hand, the level of cyclin-dependent kinase 6 ( CDK6) is dramatically and selectively elevated in parkin-expressing breast cancer cells, the extent of which correlates well with the expression of parkin. Paper-15397887. Our results show that cyclin D1 and its kinase partners CDK4 and CDK6 enhance keratinocyte proliferation, but are not sufficient to block calcium-induced keratinocyte differentiation and suggest that deregulation of these G1-regulatory kinases alone is insufficient to uncouple the link between proliferation and differentiation. Paper-15443204. 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. 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. These synonyms are used for gene CDK6 (cyclin-dependent kinase 6): Serine/threonine-protein kinase PLSTIRE, PLSTIRE, MGC59692, Cyclin-dependent kinase 6, Cell division protein kinase 6. These accession numbers are used for gene CDK6: BC065026 (NCBI_GENBANK__AC), AI400582 (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 Pan troglodytes. 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 Bos taurus. CDK6 is a homologue of CDK6 (cyclin-dependent kinase 6) from Gallus gallus. 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. Important links ! iHOP - Information Hyperlinked over Proteins . Concept & Implementation by Robert Hoffmann.