The most recent information on MXI1 is here. Click here for the function of MXI1. Edit this page in Wiki Genes - MXI1 or see Wiki Gene. Mutation of the MXI1 gene in prostate cancer. Paper-253684. Mxi1 mutations in human neurofibrosarcomas. Paper-1965404. Two cell lines harbored missense mutations in MXI1. Paper-10567961. The influence of catalysis on mad2 activation dynamics. Paper-13593579. Waiting for anaphase: Mad2 and the spindle assembly checkpoint. Paper-8604238. Genomic organization of human MXI1, a putative tumor suppressor gene. Paper-845247. We found that MXI1 LOH was independent of tumor stage and survival. Paper-1859442. Commonly occurring loss and mutation of the MXI1 gene in prostate cancer. Paper-1740433. We examined 40 primary human pancreatic adenocarcinomas for MXI1 mutations. Paper-519478. Inhibition of Mxi1 suppresses HIF-2alpha-dependent renal cancer tumorigenesis. Paper-13480339. Our data demonstrate that mutations occur in the Mxi1 gene in neurofibrosarcoma. Paper-1965404. Assignment of the human MAD and MXI1 genes to chromosomes 2p12-p13 and 10q24-q25. Paper-8173414. The MXI1 tumor suppressor gene is not mutated in primary prostate cancer. Paper-1356190. We subsequently isolated the MXI1 promoter, which is GC-rich and lacks a TATA box. Paper-8299461. Mps1 also recruits Mad1 and Mad2 to kinetochores. Paper-12835858. We sought to discover whether desmoplastic melanoma (DM) exhibited MXI1 LOH. Paper-1859442. Mad2 overexpression promotes aneuploidy and tumorigenesis in mice. Paper-12424847. Loss of heterozygosity in the MXI1 gene is a frequent occurrence in melanoma. Paper-10139083. Mxi1 isoforms are expressed in hematological cell lines and normal bone marrow. Paper-10807788. We identified Mxi1, a c-Myc antagonist, as a novel target gene induced in hypoxia. Paper-11463942. Mxi1 tumor suppressor gene is not mutated in primary pancreatic adenocarcinoma. Paper-519478. Localization of the human Mxi1 transcription factor gene ( MXI1) to chromosome 10q24-q25. Paper-8004236. Mad2 is recruited to unattached MUG kinetochores and released upon their attachment. Paper-13024189. Spindle checkpoint component Mad2 contributes to biorientation of homologous chromosomes. Paper-10119515. MXI1, a putative tumor suppressor gene, suppresses growth of human glioblastoma cells. Paper-1211315. PTEN and MXI1 allelic loss on chromosome 10q is rare in melanoma in vivo. Paper-8325618. Max interacting protein 1: loss of heterozygosity is frequent in desmoplastic melanoma. Paper-1859442. In the present study we show that Mxi1 is overexpressed in primary human clear cell kidney cancers. Paper-13480339. The Mad2 protein plays a significant role in accurate chromosome segregation in mitotic cells. Paper-9034384. Induction of Mxi1- SR alpha by FOXO3a contributes to repression of Myc-dependent gene expression. Paper-13295281. In contrast, binding of MAD2 to ADAM15 was slightly reduced by phosphorylation of the ADAM. Paper-9155871. MXI1 maps to chromosome 10q24-q25, a region that is deleted in some cases of prostate cancer. Paper-253684. Compared to Mxi1-proficient tumors, Mxi1-deficient tumors display reduced cellular proliferation. Paper-13480339. In colorectal cancer biopsies elevated expression of c-MYC correlated with increased MAD2 levels. Paper-13465984. The Mxi1 gene map to 10p24-25 and deletions of this locus are frequently observed in prostate cancers. Paper-741156. Mxi1 protects against c-Myc-dependent sensitization to hypoxia-induced apoptosis. Paper-11463942. Four polymorphisms were found in cell lines BMMNC and PBMNC: two in Mad1, one in Mxi1 and one in Rox. Paper-13306687. The Mad2 partial unfolding model: regulating mitosis through Mad2 conformational switching. Paper-13475145. Point mutations of the Mxi1 gene, if they occur, must be minor events in primary prostate cancers. Paper-741156. MAD2 expression and its significance in mitotic checkpoint control in testicular germ cell tumour. Paper-13270652. These results suggest that MXI1 is unlikely to play a role in human pancreatic adenocarcinoma tumorigenesis. Paper-519478. Mad2 and spindle assembly checkpoint function during meiosis I in mammalian oocytes. Paper-12002586. Mxi1 is thought to negatively regulate Myc function and may therefore be a potential tumor suppressor gene. Paper-1965404. The other family members, Mad1, Mxi1, Mad3, Mad4 and Rox (Mnt) antagonize their activities. Paper-8361971. Our data suggest that TCDD may increase chromosomal instability through the suppression of Mad2 expression. Paper-9034384. Mad2 is an essential component of this checkpoint system and it binds specifically to unattached kinetochores. Paper-876966. These findings support MXI1 as a putative tumor suppressor gene involved in conventional melanoma progression. Paper-10139083. We show that the roles of two spindle checkpoint components, Mad2 and Mad3, differ in meiosis I. Paper-10119515. Therefore, a substantial involvement of MXI1 gene alterations in the development of prostate cancer appears unlikely. Paper-1356190. Dioxin suppresses the checkpoint protein, MAD2, by an aryl hydrocarbon receptor-independent pathway. Paper-9034384. Furthermore, cell cycle analysis demonstrated that induction of MXI1 results in accumulation of cells in the G2-M phase. Paper-1211315. We show that purified chromosomes promote BubR1 binding to APC/C-Cdc20 by acting directly on Mad2, but not BubR1. Paper-13582004. The evidence presented here provides a link between MAD2 inactivation and malignant transformation of epithelial cells. Paper-12685197. Disruption of MAD2 expression leads to defects in the mitotic checkpoint, chromosome missegregation, and tumorigenesis. Paper-10648268. We have screened 35 late-stage bladder tumors for mutations in PTEN and MXI1, both genes mapping to chromosome 10q. Paper-10567961. Lack of deletions of the PTEN/ MMAC1 and MXI1 loci in renal cell carcinoma by interphase cytogenetics. Paper-2162488. In addition, Mad2 was not concentrated at the kinetochores, indicating that the mitotic spindle checkpoint was affected. Paper-13018400. The antibodies against cyclin B1 and MAD 2 indeed attenuated paclitaxel-induced cytotoxicity and DNA fragmentation. Paper-8556213. Differential expression of c-myc, max and mxi1 in human myeloid leukemia cells during retrodifferentiation and cell death. Paper-431478. Furthermore, attempts to disable the function of the SAC protein, Mad2, in mouse oocytes have produced conflicting results. Paper-11078928. Role of MEK/ ERK pathway in the MAD2-mediated cisplatin sensitivity in testicular germ cell tumour cells. Paper-12083909. We conclude that MXI1 gene loss in prostate cancer is common and most frequently involves a cytogenetically undetectable deletion. Paper-1740433. In normal bone marrow and hematological cell lines, the dominantly expressed isoforms are Mxi-D and full-length Mxi1 (Mxi-F). Paper-10807788. MXI1 allelic loss was seen more frequently in recurrent/metastatic tumors (59%), as compared with in primary (33%) lesions. Paper-10139083. Missense mutations in the functional domain of Mxi1 in these cases may be involved in the pathogenesis of neurofibrosarcoma. Paper-1965404. Aurora B couples chromosome alignment with anaphase by targeting BubR1, Mad2, and Cenp-E to kinetochores. Paper-9658177. Mps1 kinase activity restrains anaphase during an unperturbed mitosis and targets Mad2 to kinetochores. Paper-12835858. Mxi1 is induced by hypoxia in a HIF-1-dependent manner and protects cells from c-Myc-induced apoptosis. Paper-11463942. Such cells are blocked in metaphase, despite displaying a normal Golgi fragmentation and with the Mad2-spindle checkpoint activated. Paper-11409119. The Mad2 protein is required to delay sister chromatid separation until all chromosomes have been aligned on the mitotic spindle. Paper-12029214. One patient showed a metastatic tumor with allelic loss for MXI1 that was not identified in the primary melanoma or a local recurrence. Paper-10139083. 3. The MXI1 gene at 10q24-25 is another candidate tumor suppressor that has only rarely been studied in melanomas, with conflicting results. Paper-10139083. The MXI1 gene, located at 10q24-q25, may serve to negatively regulate c-myc oncogene activity, and potentially has tumor suppressor function. Paper-519478. In the absence of Mad2, meiosis I nondisjunction occurs at a high frequency and can be corrected by delaying the onset of anaphase. Paper-10119515. These results establish Mxi1 as an important downstream target of HIF that contributes to pVHL-deficient renal cancer tumorigenesis. Paper-13480339. Activation of a conditional c-MYC allele delayed progression through mitosis in pro-metaphase in a MAD2- and BubR1-dependent manner. Paper-13465984. A candidate tumor suppressor gene from this region, Mxi1 at 10q25, has recently been shown to be mutated in a small number of prostate tumors. Paper-398879. Correlation between methylation status and lack of expression was evident for PTEN, FGFR2, and MXI1 and was less clear for MGMT. Paper-13144573. N- APC interacts with Mad2 in Xenopus egg extracts, colon cancer cells, and in vitro with purified components. Paper-13746395. In addition, increased phosphorylation of Raf, MEK1/2 and Bcl-2 was observed in MAD2-overexpressing cells in response to vincristine. Paper-9776243. Mutation of T12 and S15 severely impairs its kinetochore association and markedly reduces recruitment of Mad2 to the kinetochore. Paper-13561502. Mitotic arrest deficient 2 ( MAD2) is thought to be a key component of the mitotic checkpoint, which ensures accurate chromosome segregation. Paper-9776243. Mad family members, including Mad1, Mxi1, Mad3, Mad4, Mnt, and Mga, function in part as antagonists of Myc oncoproteins. Paper-11810015. Interestingly, Mad2 protein expression with PXL treatment followed by 5-FU gradually increased after the PXL removal and 5-FU exposure. Paper-10840911. We prospectively evaluated prostate tumors for loss of MXI1 by fluorescence in situ hybridization (FISH) and cytogenetic techniques. Paper-1740433. Moreover, continued overexpression of Mad2 is not required for tumor maintenance, unlike the majority of oncogenes studied to date. Paper-12424847. PRP4 is a spindle assembly checkpoint protein required for MPS1, MAD1, and MAD2 localization to the kinetochores. Paper-12545761. The 25 kDa Mad2 protein is a key player in the spindle assembly checkpoint, a safeguard against chromosome segregation errors in mitosis. Paper-12611933. Unattached kinetochores catalyze production of an anaphase inhibitor that requires a Mad2 template to prime Cdc20 for BubR1 binding. Paper-13582004. We reintroduced MAD2 protein in a mitotic checkpoint-defective nasopharyngeal carcinoma cell line, CNE2, using an inducible expression vector. Paper-9776243. We have reassessed the coding sequence of MXI1 and found that, at the 3' end, the open reading frame is 28 codons shorter than previously described. Paper-266806. Bub1 has an upstream function in regulating the kinetochore localization of Mad2 and other downstream checkpoint components. Paper-11076762. The absence of mutations in these genes suggested that FAS and MXI1 are not likely to be tumor suppressor genes physiologically relevant to GBM. Paper-1380089. MAD2-induced sensitization to vincristine is associated with mitotic arrest and Raf/Bcl-2 phosphorylation in nasopharyngeal carcinoma cells. Paper-9776243. Reduced expression of MAD2 protein is associated with mitotic checkpoint abrogation and chromosomal instability in certain types of human cancers. Paper-9776243. Mad2 is a key component of the spindle assembly checkpoint, a safety device ensuring faithful sister chromatid separation in mitosis. Paper-13593579. In the absence of Aurora B function, kinetochore localization of the spindle checkpoint components BubR1, Mad2, and Cenp-E is diminished. Paper-9658177. Our findings suggest that a defective mitotic checkpoint characterized by reduced expression of MAD2 contributes to chromosomal instability in NPC. Paper-8515450. Synchronization of proliferating U-937 cells throughout distinct phases of the cell cycle exhibited little, if any, change in c-myc, c-max and mxi1 mRNAs. Paper-431478. Fluorescence in situ hybridization also demonstrated loss of one MXI1 allele in an additional tumour lacking chromosome 10 abnormalities. Paper-253684. Deletions in the long arm of chromosome 10 in lymphomas with t(14;18): a pathogenetic role of the tumor supressor genes PTEN/ MMAC1 and MXI1? Paper-1670452. Genotype fidelity with respect to MXI1 status was present in two patients from whom primary and recurrent tumor was available for comparative analysis. Paper-1859442. We detected a silent mutation in the HLH region, but no point mutations reflecting the functional change of Mxi1 were found in human prostate cancers. Paper-741156. We have recently reported a new link between an important cell cycle timer/regulator, MAD2, and the cytokine, stem cell factor, and its receptor. Paper-13130273. The template model proposes that Mad1- Mad2 at kinetochores acts as a template to change the conformation of another binding molecule of Mad2. Paper-11199549. Max interacting protein 1 ( MXI1), a negative regulator of myc oncoprotein with tumor suppressor properties, has been mapped to chromosome 10q24-25. Paper-1859442. Mxi1 protein is a basic helix-loop-helix, leucine zipper (bHLHZIP) transcriptional factor, which dimerizes with the Max protein. Paper-10807788. Surprisingly, 4E-BP1 knock-down also leads to a dramatic increase in aberrant mitoses in vivo and enhanced expression of Mad2 and securin. Paper-13055816. Treatment of cells expressing high levels of MAD2 with an MEK inhibitor, U0126, led to cellular protection against cisplatin-induced apoptosis. Paper-12083909. Five of 11 DMs in subjects informative for the MXI1 microsatellite manifested MXI1 allelic imbalance consistent with tumor suppressor LOH. Paper-1859442. This delay is characterised by the recruitment of Mad2 protein to a few KTs and the occasional loss of individual chromosomes from the metaphase plate. Paper-12337932. New work highlights the importance of the Mad2- Mad2 interaction, and suggests how spindle checkpoint signals are propagated away from kinetochores. Paper-10733983. Our results define a clear role for Mad2 in ensuring the proper timing of meiosis I events and ultimately, in ensuring the fidelity of homologue disjunction. Paper-11078928. Nine missense mutations were detected: two in Mad1 in patients, four in Mxi1 (three in patients and one in KG-1 cell line), and three in Rox in patients. Paper-13306687. MXI1 LOH seems to be a relatively frequent and early event in DM development and progression, consistent with neuroectodermal histogenesis of the neoplasm. Paper-1859442. Therefore, two human tumor cell lines ( MXI and S117) and a renal tubular cell line (Landa Leiden) were exposed to 4-hydroxy-IFO, CAA, and a combination of both. Paper-1075243. Furthermore, although catalytically inactive Mps1 can restore kinetochore localization of Mad1, only the active kinase restores Mad2 localization. Paper-12835858. Thus, we find that PRP4 is necessary for recruitment or maintenance of the checkpoint proteins MPS1, MAD1, and MAD2 at the kinetochores. Paper-12545761. No mutations were found in these two important coding regions and we therefore conclude that MXI1 does not make a major contribution to prostate cancer susceptibility. Paper-1201940. Our results show that overexpression of Mxi1 does in fact inhibit ODC gene expression in a dose-dependent manner both in vivo and in vitro. Paper-549934. Sequence analysis revealed no somatic mutations in any of the six MXI1 coding exons, similar to findings in prostate tumors with MXI1 allelic loss. Paper-1211315. Colorectal adenocarcinoma (n = 21) and astrocytomas (n = 19) were similarly analyzed, serving as negative and positive controls, respectively, for MXI1 LOH. Paper-1859442. We found that overexpression of MAD2 led to an increased sensitivity to vincristine, which was accompanied by increased mitotic index and G2/M cell cycle arrest. Paper-9776243. In this study, we investigated whether MAD2 played a role in cellular sensitivity to cisplatin in TGCT cells and the underlying molecular mechanisms responsible. Paper-12083909. The correspondence of these exons to previously identified Mxi1 functional domains suggests that alternatively spliced transcripts may regulate Mxi1 functional activity. Paper-845247. MXI1, a member of the MYC family of transcription factors, is thought to negatively regulate MYC function and may therefore be a potential tumor suppressor gene. Paper-845247. Using a combination of somatic cell mapping and fluorescence in situ hybridization techniques, we have determined the chromosomal locations of the MAD and MXI1 genes. Paper-8173414. These studies provide further insight into the complex regulatory mechanisms governing MXI1 gene expression and its role in cellular differentiation and tumor suppression. Paper-8299461. MXI1 thus displays allelic loss and mutation in some cases of prostate cancer that may contribute to the pathogenesis or neoplastic evolution of this common malignancy. Paper-253684. One candidate upregulated gene ( MXI1) was validated as having increased expression in advanced stage (T4) carcinomas by real-time PCR (p<0.05) and immunolabeling (p<0.003). Paper-12993731. Our study suggests that activation of cyclin B1/ CDC 2 and MAD 2 were the M-phase events required for paclitaxel- induced apoptosis in NPC cells. Paper-8556213. However, no mutations or homozygous deletions were found in the coding region of MXI1, a candidate tumor suppressor gene at 10q24-q25, in a panel of SCLC cell lines. Paper-1616657. Previously, we first reported that a key regulator of the mitotic checkpoint, mitotic arrest deficient-2 ( MAD2), was a mediator of cisplatin sensitivity in human cancer cells. Paper-12083909. MXI1 gene loss, demonstrated by loss of heterozygosity ( LOH) analysis ( allelic imbalance), is a frequent event in astrocytomas and other forms of glial neoplasia. Paper-1859442. The MXI1 gene localizes to chromosome 10q24-q25, a region involved in translocations and deletions in acute and chronic lymphocytic leukemias and prostatic carcinomas. Paper-8173414. MXI1, a member of the MAD family of Myc antagonists, encodes a transcription factor whose expression must be tightly regulated to maintain normal cell growth and differentiation. Paper-8299461. The dys-regulated cyclin B1/ CDC 2 activation could enhance the prometaphase progression, but activation of MAD 2 rendered cells inable to exit from the metaphase. Paper-8556213. Our results suggest that Rab6A' likely regulates the dynamics of the dynein/dynactin complex at the kinetochores and consequently the inactivation of the Mad2-spindle checkpoint. Paper-11409119. c-MYC delays prometaphase by direct transactivation of MAD2 and BubR1: identification of mechanisms underlying c-MYC-induced DNA damage and chromosomal instability. Paper-13465984. Finally, we have identified two polymorphic regions within the MXI1 locus: a polymorphic CA repeat in the third intron and an AAAAC polymorphism in the noncoding region of exon 6. Paper-845247. Double mutant and inhibitor analyses revealed that Dis3 is required for correct kinetochore formation and function, and that this activity is monitored by the Mad2 checkpoint. Paper-12468621. Fifty-four percent (15 of 28) of the informative cases showed loss of heterozygosity for one or both MXI1 markers, as compared with 67% (16 of 24) of the informative cases for MTS1. Paper-10139083. Our results also suggest that downregulation of MAD2 may be an indicator for identification of TGCT cancer cells that are potentially resistant to cisplatin-based therapy. Paper-12083909. Conformational dimerization of Mad2 is essential to accelerate Cdc20 binding, but it does not modify the equilibrium of the Mad2:Cdc20 interaction, i.e., it is purely catalytic. Paper-13593579. The metamorphic Mad2 protein acts as a molecular switch in the checkpoint mechanism that monitors proper chromosome attachment to spindle microtubules during cell division. Paper-13475145. Kinetochores also retain detectable levels of the spindle checkpoint proteins Mad2 and BubR1, as expected for activation of the spindle checkpoint by unattached kinetochores. Paper-9269232. These proteins include the microtubule motors CENP-E and cytoplasmic dynein, and proteins involved with the mitotic spindle checkpoint, Mad2, Bub1R, and the 3F3/2 phosphoantigen. Paper-8889956. We and others have previously mapped the MXI1 gene to the distal portion of chromosome 10q, a region that is rearranged or affected by allelic loss in many astrocytic brain tumors. Paper-1211315. Here, we provide evidence for this fundamental assumption and demonstrate that conformational dimerization of Mad2 accelerates the rate of Mad2 binding to Cdc20. Paper-13593579. Thus, these studies support the notion that MXI1 normally functions to suppress cell growth and suggest that loss of MXI1 function may play a role in human glioblastoma development. Paper-1211315. Taken together, these findings suggested differential regulation and inverse expression levels of c-myc compared to c-max and mxi1 during differentiation, retrodifferentiation and cell death. Paper-431478. PICH contributes to the mitotic checkpoint by recruiting Mad2 to kinetochores and is proposed to regulate checkpoint signaling by monitoring tension at centromeres. Paper-12403805. Using a newly described polymorphic CA microsatellite repeat in the third MXI1 intron, we show that 7 of 11 informative glioblastomas demonstrated MXI1 allelic loss. Paper-1211315. Mtor/Tpr promotes the recruitment of Mad2 and Mps1 but not Mad1 to unattached kinetochores (KTs), mediating normal mitotic duration and SAC response. Paper-13656728. LD doxorubicin-induced SLP was preceded by multinucleation and downregulation of multiple proteins with mitotic checkpoint function, including CENP-A, Mad2, BubR1, and Chk1. Paper-11005637. Also, postovulatory and in vitro aging of mouse oocytes has been shown to lead to decreased levels of Mad2 transcripts and elevated frequencies of premature centromere separation. Paper-12957654. We also examined 29 human tumor cell lines consisting of 12 esophageal cancers, 7 glioma/ glioblastomas and 10 others for Mxi1 mutations in exons 1, 2, 4 (HLH domain), 5 and 6. Paper-1965404. Activation of MAD 2 checkprotein and persistence of cyclin B1/ CDC 2 activity associate with paclitaxel- induced apoptosis in human nasopharyngeal carcinoma cells. Paper-8556213. These results demonstrate that transient Mad2 overexpression and chromosome instability can be an important stimulus in the initiation and progression of different cancer subtypes. Paper-12424847. To gain further insight into SAC function during female mammalian meiosis I, we recently utilised a morpholino-based antisense approach to deplete the majority of Mad2 in mouse oocytes. Paper-11078928. However, formation of Max/ Mxi1 or Max/Mad heterodimers results in a reduction in Myc/Max dependent transcriptional activation of reporter plasmid constructs containing the consensus element. Paper-549934. First, gain of cMYC and loss of cMYC antagonists ( MXI1 and MNT) were observed in 75% and 40% to 55% of patients, respectively, which were frequently associated with deregulated gene expression. Paper-12780717. Furthermore, the chromosome-produced inhibitor requires both recruitment of Mad2 by Mad1 that is stably bound at unattached kinetochores and dimerization-competent Mad2. Paper-13582004. We found that male fertility and accurate chromosome segregation during spermatogenesis are highly dependent on BubR1, but not Mad2, Bub3, Rae1 and Nup98. Paper-12069969. The induction of Mxi1 by FOXO3a was specific to the Mxi1- SR alpha isoform and was mediated by three highly conserved FOXO binding sites within the first intron of the gene. Paper-13295281. Using 10 TGCT cell lines, we found that increased MAD2 expression was correlated with cellular sensitivity to cisplatin, which was associated with activation of the MEK pathway. Paper-12083909. Inactivation of the MXI1 gene could, therefore, inhibit differentiation and enhance proliferation in the presence of normal levels of c-Myc, and thus MXI1 is a potential tumor suppressor gene. Paper-1211315. After clarification of the 5'- and 3'-untranslated regions of the cDNA (indicating that the true length of the MXI1 transcript is 2643 base pairs), we identified two transcription initiation sites. Paper-8299461. Furthermore, suppression of spindle checkpoint function by BubR1 or Mad2 RNA interference in the DNA damaged cells led to escape from catastrophic death and to subsequent abnormal mitosis. Paper-10537055. We screened the 10q locus for loss of heterozygosity and the promoter methylation status of PTEN, MGMT, MXI1, and FGFR2 in neuroblastic tumors and neuroblastoma cell lines. Paper-13144573. In addition, we utilized SSCP analysis to test two other candidate genes on 10q: FAS, a cell surface receptor which transduces an apoptotic, cell death signal and MXI1, a transcriptional repressor. Paper-1380089. Max is able to form homodimers and heterodimers with other members of this family, which include Mad, Mxi1 and Myc; Myc is an oncoprotein implicated in cell proliferation, differentiation and apoptosis. Paper-1022750. Accurate chromosome segregation in meiosis I depends on spindle checkpoint proteins such as Mad2 which delay APC/C activation in response to an erroneous spindle attachment of chromosomes. Paper-11368198. Inhibition of Mxi1 in pVHL-defective kidney cancer cells using shRNA alters their cell cycle parameters, inhibits their ability to invade matrigel, and suppresses their ability to form tumors in vivo. Paper-13480339. The distal long arm of chromosome 10 harbors genes of biomedical interest such as MXI1, a putative tumor suppressor gene, and those encoding the adrenergic receptors alpha2A (ADRA2A) and beta1 ( ADRB1). Paper-1300952. We analyzed most of the coding region of the Mxi1 gene, including these three important regions in 32 prostate cancers and three cell lines by PCR-single strand conformational polymorphism ( SSCP). Paper-741156. The mitotic arrest deficient 2 ( MAD2) is suggested to play a key role in a functional mitotic checkpoint because of its inhibitory effect on anaphase-promoting complex/cyclosome ( APC/C) during mitosis. Paper-12685197. Prophase-arrested cells exhibited randomly oriented spindle structures, whereas metaphase cells exhibited aberrant bipolar spindles with Mad2 localization at kinetochores of misaligned chromosomes. Paper-9169281. Furthermore, Mad2 up-regulation in these cells suggested that overexpression of spindlin1 may affect the bipolar spindle correctly attachment to chromosomes and activate spindle checkpoint. Paper-12920726. Suppression of Mad2 was also observed in aryl hydrocarbon receptor-deficient mouse embryonic fibroblasts, suggesting that TCDD suppresses Mad2 by a novel TCDD receptor signaling mechanism. Paper-9034384. Two Developmental Cell papers in this issue by Kulukian et al. and Malureanu et al. now provide insight into how checkpoint components Mad2 and BubR1 relay the checkpoint signal from kinetochores to APC/C. Paper-13581995. The MXI1 gene encodes a protein interacting with Max, a regulatory factor of the Myc oncogene, and is located on chromosome 10q25, a region showing frequent loss of heterozygosity in malignant gliomas. Paper-266806. The oncogene MXI1 on chromosome band 10q24-25 is mutated in a proportion of prostate tumours and loss of heterozygosity occurs at this site, suggesting the location of a tumour suppressor in this region. Paper-1201940. Mps1 acts upstream in the spindle checkpoint signaling cascade, and kinetochore targeting of Mps1 is required for subsequent recruitment of Mad1 and Mad2 to the kinetochore. Paper-13561502. Mxi1, a c-Myc antagonist, is a HIF target gene that inhibits mitochondrial biogenesis, reprograms cellular energy metabolism, and protects cells from c-Myc-dependent apoptosis in vitro. Paper-13480339. Furthermore, like c-myc, c-max and mxi1 mRNA transcripts appeared to be regulated primarily by post-transcriptional mechanisms, and c-max and mxi1 half-lives exceeded 4 h in contrast to < 60 min for the c-myc gene. Paper-431478. The major changes observed were an up-regulation of c-Fos and Fra-1 and a decrease in c-Myc at the time of commitment, followed by an increase in Mad, Mxi1, Fra-2 and JunB expression at the onset of differentiation. Paper-388042. MAD2 is localized to kinetochores of unaligned chromosomes, where it inactivates the anaphase-promoting complex/cyclosome, thus contributing to the production of a diffusible anaphase inhibitory signal. Paper-10648268. Reducing the levels of the checkpoint proteins BubR1 or Mad2 in human cancer cells or inhibiting BubR1 kinase activity provokes apoptotic cell death within six divisions except when cytokinesis is also inhibited. Paper-10345444. Redefinition of the coding sequence of the MXI1 gene and identification of a polymorphic repeat in the 3' non-coding region that allows the detection of loss of heterozygosity of chromosome 10q25 in glioblastomas. Paper-266806. We identified MXI1 LOH in neoplastic tissue by observing allelic imbalance for a microsatellite repeat polymorphism in the 3' nontranslated region of the MXI1 gene in subjects shown to be informative. Paper-1859442. No germline mutations in the dimerization domain of MXI1 in prostate cancer clusters. The CRC/BPG UK Familial Prostate Cancer Study Collaborators. Cancer Research Campaign/British Prostate Group. Paper-1201940. MXI1 mutation appears to play a role in the pathogenesis of a small subset of cases, and suggests an alternative mechanism to MYC amplification for disruption of the MYC/MAD/ MAX network in medulloblastoma. Paper-12320459. Cross-referencing data with that found in HNSCC, we were able to identify a tumor suppressor gene involved in the c-myc pathway ( Mxi1) that was similarly under-expressed in smokers and cancer patients with progressive disease. Paper-12078472. Inactivation of MAD2 by transfecting a dominant-negative construct in TGCT cells with high levels of MAD2 resulted in the suppression of MEK pathway and resistance to cisplatin-induced cell death. Paper-12083909. We also found that approximately 60% of CENP-C-deficient cells had no Mad2 signals even after treatment with nocodazole, suggesting that lack of CENP-C impairs the Mad2 spindle checkpoint pathway. Paper-13257152. The Mxi1 protein functions in a regulatory network with members of the c-Myc family, in which c-Myc activates transcription and stimulates cell proliferation, and Mxi1 negatively regulates these actions. Paper-1211315. Several serum deprivation early response genes (SDERGs), including the putative tumor suppressor genes SALL2 and MXI1, are required for cessation of DNA synthesis in response to SD and induction of additional SD genes. Paper-13378668. For prostate cancer, allelic deletions from the long arm of chromosome 10 (#10q23-25), the locus of the putative tumor suppressor gene MXI1 (#10q24-25), have been identified as a frequently occurring genetic event. Paper-1356190. In different organisms, a mitotic checkpoint complex (MCC) composed of Mad2, Bub3, BubR1/ Mad3, and Cdc20 inhibits the anaphase promoting complex ( APC/C) to initiate promotion into anaphase. Paper-13491278. In an effort to gain insight into the network of these four proteins we have started to analyse the expression of the c-myc, max, mad and mxi1 genes at the mRNA level during hematopoietic cell growth and differentiation. Paper-8175078. Mad2 is an essential component of the spindle checkpoint that blocks activation of Separase and dissolution of sister chromatids until microtubule attachment to kinetochores is complete. Paper-12424847. The aim of this study was to investigate the function of mitotic checkpoint control in TGCT cells and to study its association with MAD2 expression using 8 TGCT cell lines as well as 23 TGCT tissue samples. Paper-13270652. When bound to DNA by a LexA moiety in yeast, Mxi1 does not stimulate transcription. mxi1 mRNA is expressed in many tissues, and its expression is elevated in U-937 myeloid leukemia cells that have been stimulated to differentiate. Paper-81701. Between 7 and 11 days of TPA-induced G0/G1 cell cycle arrest, expression of the c-max and mxi1 genes continuously increased up to 8-fold until 32 days and declined to control levels when the cells regained proliferative capacity by 36 days. Paper-431478. Due to the detection of point mutations in the retained alleles of four primary adenocarcinomas of the prostate, MXI1 gene alterations have been suggested to be involved in the development and/or the progression of prostate cancer. Paper-1356190. The results suggest a coordinated mechanism for opposing c-Myc signaling during hypoxia that is mediated by a reduction in c-Myc levels, the induction of Mxi1, and a dominant effect of HIF-1 transcriptional activity. Paper-11463942. We show that RNA interference depletion of LIC in Drosophila S2 cells does not block the recruitment of a dynein complex to kinetochores, but it does delay inactivation of Mad2 signaling and mitotic progression. Paper-13059679. Mitoticarrest deficient 2 ( MAD2) depletion rescued the caffeine-induced delay of mitotic exit, indicating that caffeine-induced prolongation of mitosis was caused by activation of a MAD2-dependent spindle checkpoint. Paper-12922116. In addition, analysis of repressed genes supported a model for antagonism of c-Myc signaling in hypoxia, based on the downregulation of several known c-Myc target genes and the induction of Mxi1, a c-Myc antagonist. Paper-13461189. To determine whether MXI1 can indeed function as a suppressor of growth, we have introduced a steroid-inducible MXI1 expression vector into the U87MG cell line, a glioblastoma cell line lacking endogenous MXI1 expression. Paper-1211315. These findings implicate the inactivation of critical TS loci at 10q23.3-25.3 in medulloblastoma, however comprehensive analysis of SUFU, BTRC and MXI1 indicates they are unlikely to represent major targets of these allelic losses. Paper-12320459. Here we show that the human BubR1 and MAD2 genes, which encode inhibitors of the anaphase promoting complex ( APC/C), are directly activated by the oncogenic transcription factor c-MYC via E-box sequences in their first introns. Paper-13465984. Dynein/dynactin inhibition did not block chromosome congression to the spindle equator in prometaphase, or segregation to the poles in anaphase when the spindle checkpoint was inactivated by microinjection with Mad2 antibodies. Paper-8889956. Metaphase delay and increased interkinetochore distances are suppressed by depletion of Mad1, Mad2 or BubR1 or by re-expression of wtLIC1 or a Cdk1 site phosphomimetic LIC1 mutant, but not Cdk1-phosphorylation-deficient LIC1. Paper-13707775. Treatment of U-937 cells with 12-O-tetradecanoyl phorbol-13-acetate (TPA) which is associated with the induction of a monocytic differentiation program and growth arrest, revealed an initial up-regulation of c-myc, c-max, and mxi1 mRNAs after 1-6 h. Paper-431478. The interaction between N- APC and Mad2 decreases the soluble pool of Mad2, which is essential for Mad2 cycling and releasing from unattached kinetochores to produce a diffusible |P;wait anaphase|P' signal. Paper-13746395. Aurora B plays a role in the spindle assembly checkpoint, in part, by destabilizing the localization of BubR1 and Mad2 at centrosomes and responds to changes in tension caused by aberrant microtubule kinetochore attachments. Paper-13517098. Patients with nodal diffuse large B-cell lymphomas (DLBCL) at a single institute (n=44) were studied for methylation of tumor-related genes, MGMT, p15(INK4B), p16(INK4A), p16(INK4A), Mad2, TMS1/ ASC, CASP8, and GSTP1. Paper-13630276. METHODS: We employed reverse transcription and real-time fluorescent PCR to quantify the expression of nine genes ( BRCA1, BRCA2, ATM, TP53, RB1, MAD2, BUB1, APC and beta-actin) in oocytes and embryos. Paper-11027045. Although a consistent pattern did not emerge among the markers, LOH of 9p21 (D9S254) occurred in 60% (9/15) of the cases followed by 40% of cases displaying LOH of 1p34, p53, 10q ( MXI1), and 10q23 (D10S520) and 25% with 5q21 (D5S 592) abnormalities. Paper-9707622. This loss of mitotic checkpoint control was correlated with reduced MAD2 protein expression in TGCT cell lines implicating that downregulation of MAD2 may play a critical role in an impaired mitotic checkpoint control in these cells. Paper-13270652. 3. This region contains three genes, MXI1, SUFU and BTRC, which represent putative medulloblastoma tumor suppressor (TS) genes on the basis of either (i) negative regulation of critical medulloblastoma pathways, or (ii) mutation in other cancer types. Paper-12320459. Disruption of Mad2, BubR1, Bub3 or Rae1 in mice results in substantial aneuploidy in somatic tissues, but whether these genes are equally important for accurate chromosome segregation during meiosis has not yet been established. Paper-12069969. These results support previous suggestion on the involvement of mitotic checkpoint in DNA damage response in human cancer cells and demonstrate a possible molecular mechanism responsible for the MAD2- mediated sensitivity to cisplatin in TGCT cells. Paper-12083909. Frequent inactivation of PTEN/ MMAC1 tumor suppressor gene at 10q23, MXI-1 at 10q25, KAI-1 at 11p11.2, Rb at 13q14.2, and p53 at 17p13.1 and deregulation of c-myc oncogene at 8q24 have recently been the subject of intense scrutiny and debate. Paper-1935768. Through binding to its target Cdc20, Mad2 inhibits the multisubunit ubiquitin ligase, the anaphase-promoting complex or cyclosome ( APC/C), and delays the onset of anaphase until all sister chromatids achieve bipolar attachment to the mitotic spindle. Paper-13089509. We show here that overexpression of Mad2 in transgenic mice leads to a wide variety of neoplasias, appearance of broken chromosomes, anaphase bridges, and whole-chromosome gains and losses, as well as acceleration of myc-induced lymphomagenesis. Paper-12424847. To investigate the involvement of cyclin B1 and MAD 2 activation in paclitaxel-induced apoptosis, we introduced affinity-purified anti-cyclin B1 and MAD 2 antibodies into NPC cells by electroporation before the further paclitaxel treatment. Paper-8556213. Our results support a model in which immobilized Mad1/ Mad2 at kinetochores provides a template for initial assembly of Mad2 bound to Cdc20 that is then converted to a final mitotic checkpoint inhibitor with Cdc20 bound to BubR1. Paper-13582004. In addition, we found that GL331-induced perturbation of cell cycle progression dramatically over-rode the patterns of mitotic arrest induced by paclitaxel, and the mechanism could be the inhibition of cyclin B1/ CDC2 kinase and MAD2 checkprotein activities. Paper-8774444. This observation suggests that Mad2 plays a role in reorienting chromosomes that are incorrectly attached to the spindle as well as delaying the cell cycle, whereas Mad3 is needed for the cell cycle delay, but not for chromosome reorientation. Paper-10119515. Using physiologically relevant levels of Mad2, Bub3, BubR1, and Cdc20, we demonstrate that unattached kinetochores on purified chromosomes catalytically generate a diffusible Cdc20 inhibitor or inhibit Cdc20 already bound to APC/C. Paper-13582004. In this study, we stably transfected a C-terminal-deleted MAD2 gene (MAD2DeltaC) into a human prostate epithelial cell line, Hpr-1 and studied its effect on chromosomal instability, cell proliferation, mitotic checkpoint control and soft agar colony-forming ability. Paper-12685197. We found that MAD2DeltaC was able to induce aneuploidy through promoting chromosomal duplication, which was a result of an impaired mitotic checkpoint and cytokinesis, suggesting a crucial role of MAD2-mediated mitotic checkpoint in chromosome stability in human cells. Paper-12685197. In addition, immunohistochemistry studies on 23 seminomas and 12 normal testis tissues demonstrated that nuclear expression of MAD2 was much lower in seminomas (p<0.0001) but cytoplasmic MAD2 expression was higher in seminomas (p=0.06) than normal samples. Paper-13270652. To investigate the possibility that MXI1 may be involved in inherited susceptibility to prostate cancer, we have sequenced the HLH and ZIP regions of the gene in 38 families with either three cases of prostate cancer or two affected siblings both diagnosed below the age of 67 years. Paper-1201940. The combination of MDI and Aerochamber was significantly better at delivering budesonide to a filter in front of the test lung (14.2% of aerosolized dose) than were either the MDI and Aerovent (3.6%) or the Ultravent or MAD2 jet nebulizers (0.02% and 0.68% of initial reservoir dose). Paper-7497368. We compared the delivery of a micronized suspension of budesonide by a metered dose inhaler (MDI) with two different spacers (Aerochamber and Aerovent) and by two jet nebulizers ( MAD2 and Ultravent) to a ventilated neonatal test-lung using a standard neonatal ventilator circuit. Paper-7497368. The Myc antagonists Mad1, Mxi1 and Rox proteins share two highly conserved domains, Sin3-interacting domain ( SID) and basic helix-loop-helix leucine zipper domain (bHLHzip), which are essential for these proteins to function during molecular switching from proliferation to differentiation. Paper-13306687. We next identified and characterised CpG islands associated with 5' regions of the MXI1, SUFU and BTRC genes; analysis of these regions for evidence of DNA hypermethylation, alongside expression analysis of their respective transcripts, revealed no evidence to support epigenetic inactivation of any gene. Paper-12320459. METHODS: Transient reporter assays and trichostatin A ( TSA) experiments were performed to evaluate several candidate genes, including Mxi1, c-myc promoter binding protein 1 ( MBP-1), Miz, and histone deacetylase 2 ( HDAC2), for their involvement in N-myc autoregulation. Paper-10604061. In this report, we show that Megator ( Mtor), the Drosophila melanogaster counterpart of the human nuclear pore complex protein translocated promoter region (Tpr), and the spindle assembly checkpoint (SAC) protein Mad2 form a conserved complex that localizes to a nuclear derived spindle matrix in living cells. Paper-13656728. To prevent chromosome missegregation due to early degradation of cyclin B and securin, mitotic checkpoint protein complexes consisting of BubR1, Bub3 and Mad2 bind to and inhibit APC(Cdc20) until all chromosomes are properly attached to the mitotic spindle and aligned in the metaphase plate. Paper-12069969. Although both m-calpain RNAi and calpain inhibitors affected neither the separation of centrosomes nor the assembly of bipolar spindles, Mad2 was detected on the kinetochores of the misaligned chromosomes, indicating that the prometaphase arrest induced by calpain inhibition is due to activation of the spindle assembly checkpoint. Paper-10220278. We propose that Mtor/Tpr functions as a spatial regulator of the SAC, which ensures the efficient recruitment of Mad2 to unattached KTs at the onset of mitosis and proper spindle maturation, whereas enrichment of Mad2 in a spindle matrix helps confine the action of a diffusible "wait anaphase" signal to the vicinity of the spindle. Paper-13656728. The C-terminal region of Mad2 that undergoes rearrangement in different Mad2 conformers is a major structural determinant for p31(comet) binding, explaining the specificity of p31(comet) toward Mad1- or Cdc20- bound Mad2. p31(comet) adopts a fold strikingly similar to that of Mad2 and binds at the dimerization interface of Mad2. Paper-12611934. These synonyms are used for gene MXI1 (MAX interactor 1): Protein MXI1, MXI, MXD2, MGC43220, MAX-interacting protein 1, MAD2, bHLHc11. These accession numbers are used for gene MXI1: Q6FHW2 (UNIPROT__AC), Q15887 (UNIPROT__AC), AAD14282 (NCBI_GENBANK__AC), AAA75508 (NCBI_GENBANK__AC). MXI1 is a homologue of MXI1 (MAX interactor 1) from Bos taurus. MXI1 is a homologue of MXI1 (MAX interactor 1) from Pan troglodytes. MXI1 is a homologue of MXI1 (MAX interactor 1) from Gallus gallus. MXI1 is a homologue of MXI1 (MAX interactor 1) from Canis lupus familiaris. MXI1 is a homologue of Mxi1 (Max interacting protein 1) from Mus musculus. Important links ! iHOP - Information Hyperlinked over Proteins . Concept & Implementation by Robert Hoffmann.