MAD2 dependent mitotic checkpoint defects in tumorigenesis and tumor cell death: A double edged sword Journal Article
| Authors: | Michel, L.; Benezra, R.; Diaz-Rodriguez, E. |
| Article Title: | MAD2 dependent mitotic checkpoint defects in tumorigenesis and tumor cell death: A double edged sword |
| Abstract: | The failure of cell cycle regulatory checkpoints is a common event in human cancer. Defects at the G1-S transition have been widely characterized, but only more recently has aberrant checkpoint signaling during mitotic progression been identified as playing a role in cancer. The metaphase to anaphase transition is regulated by multiple proteins that together comprise the mitotic checkpoint. Previously it has been shown that loss of one copy of MAD2, a mitatic checkpoint gene, results in aneuplaidy and tumorigenesis arising from chromosome missegregation. More recently and quite surprisingly, MAD2 has been demonstrated to be an essential gene even in tumor cells such that near complete elimination of this protein from cancer cells results in p53 independent cell death. This is the first identification of a haploinsufficient tumor suppressor gene that is also required for tumor cell survival, and suggests that targeting this checkpoint in cancer might be a viable therapeutic strategy. |
| Keywords: | unclassified drug; human cell; review; nonhuman; mitosis; animal cell; animals; cell cycle proteins; cell death; cell survival; cell cycle; cell cycle s phase; apoptosis; protein depletion; protein p53; cancer therapy; carcinogenesis; cell transformation, neoplastic; nuclear proteins; regulatory mechanism; gene loss; anaphase; cyclin b; microtubule; microtubules; aneuploidy; cell cycle g1 phase; metaphase; chromosome segregation; regulator protein; mitotic checkpoint; securin; tumor cell destruction; protein mad2; mad2; essential gene; humans; human; multi-nucleation |
| Journal Title: | Cell Cycle |
| Volume: | 3 |
| Issue: | 8 |
| ISSN: | 1538-4101 |
| Publisher: | Taylor & Francis Inc. |
| Date Published: | 2004-08-01 |
| Start Page: | 990 |
| End Page: | 992 |
| Language: | English |
| PROVIDER: | scopus |
| PUBMED: | 15254432 |
| DOI: | 10.4161/cc.3.8.1058 |
| DOI/URL: | |
| Notes: | Cell Cycle -- Cited By (since 1996):17 -- Export Date: 16 June 2014 -- Source: Scopus |
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