A Double Edged Sword: MAD2 Dependent Mitotic Checkpoint Defects in Tumorigenesis and Tumor Cell Death

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 anaphas...

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Bibliographic Details
Published inCell cycle (Georgetown, Tex.) Vol. 3; no. 8; pp. 988 - 990
Main Authors Michel, Loren, Benezra, Robert, Diaz-Rodriguez, Elena
Format Journal Article
LanguageEnglish
Published Taylor & Francis 21.08.2004
Subjects
Binding
Biology
Bioscience
Calcium
Cancer
Cell
Cycle
Landes
Organogenesis
Proteins
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Summary: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 mitotic checkpoint gene, results in aneuploidy 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.
ISSN:1538-4101
1551-4005
DOI:10.4161/cc.3.8.1058