Deficiency in SNM1 abolishes an early mitotic checkpoint induced by spindle stress

被引:30
作者
Akhter, S
Richie, CT
Deng, JM
Brey, E
Zhang, XS
Patrick, C
Behringer, RR
Legerski, RJ
机构
[1] Univ Texas, MD Anderson Canc Ctr, Dept Mol Genet, Houston, TX 77030 USA
[2] Univ Texas, MD Anderson Canc Ctr, Dept Plast Surg, Houston, TX USA
关键词
D O I
10.1128/MCB.24.23.10448-10455.2004
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Spindle poisons represent an important class of anticancer drugs that act by interfering with microtubule polymerization and dynamics and thereby induce mitotic checkpoints and apoptosis. Here we show that mammalian SNM1 functions in an early mitotic stress checkpoint that is distinct from the well-characterized spindle checkpoint that regulates the metaphase-to-anaphase transition. Specifically, we found that compared to wild-type cells, Snm1-deficient mouse embryonic fibroblasts exposed to spindle poisons exhibited elevated levels of micronucleus formation, decreased mitotic delay, a failure to arrest in mitosis prior to chromosome condensation, supernumerary centrosomes, and decreased viability. In addition, we show that both Snm1 and 53BP1, previously shown to interact, coimmunoprecipitate with components of the anaphase-promoting complex (APC)/cyclosome. These findings suggest that Snm1 is a component of a mitotic stress checkpoint that negatively targets the APC prior to chromosome condensation.
引用
收藏
页码:10448 / 10455
页数:8
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