Journal
JOURNAL OF CELL BIOLOGY
Volume 178, Issue 2, Pages 283-296Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.200702134
Keywords
-
Categories
Funding
- NCI NIH HHS [P30 CA021765, CA21765] Funding Source: Medline
- NCRR NIH HHS [RR04050, P41 RR004050] Funding Source: Medline
- NIGMS NIH HHS [R01 GM068418, GM68418] Funding Source: Medline
Ask authors/readers for more resources
The spindle checkpoint that monitors kinetochore-microtubule attachment has been implicated in tumorigenesis; however, the relation between the spindle checkpoint and cell death remains obscure. In BUB1 deficient (but not MAD2-deficient) cells, conditions that activate the spindle checkpoint (i.e., cold shock or treatment with nocodazole, paclitaxel, or 17-AAG) induced DNA fragmentation during early mitosis. This mitotic cell death was independent of caspase activation; therefore, we named it caspase-independent mitotic death (CIMD). CIMD depends on p73, a homologue of p53, but not on p53. CIMD also depends on apoptosis-inclucing factor and endonuclease G, which are effectors of caspase-independent cell death. Treatment with nocodazole, paclitaxel, or 17-AAG induced CIMD in cell lines derived from colon tumors with chromosome instability but not in cells from colon tumors with microsatellite instability. This result was due to low BUB1 expression in the former cell lines. When BUB1 is completely depleted, aneuploidy rather than CIMD occurs. These results suggest that cells prone to substantial chromosome missegregation might be eliminated via CIMD.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available