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Genome‐wide si RNA screen reveals coupling between mitotic apoptosis and adaptation
Author(s) -
DíazMartínez Laura A,
Karamysheva Zemfira N,
Warrington Ross,
Li Bing,
Wei Shuguang,
Xie XianJin,
Roth Michael G,
Yu Hongtao
Publication year - 2014
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.201487826
Subject(s) - biology , mitosis , microbiology and biotechnology , mitotic catastrophe , cell cycle checkpoint , mitotic exit , apoptosis , crosstalk , cell cycle , mitochondrion , spindle checkpoint , mitochondrial fission , spindle apparatus , cell division , genetics , cell , anaphase , physics , optics
The antimitotic anti‐cancer drugs, including taxol, perturb spindle dynamics, and induce prolonged, spindle checkpoint‐dependent mitotic arrest in cancer cells. These cells then either undergo apoptosis triggered by the intrinsic mitochondrial pathway or exit mitosis without proper cell division in an adaptation pathway. Using a genome‐wide small interfering RNA (si RNA ) screen in taxol‐treated H e L a cells, we systematically identify components of the mitotic apoptosis and adaptation pathways. We show that the M ad2 inhibitor p31 comet actively promotes mitotic adaptation through cyclin B 1 degradation and has a minor separate function in suppressing apoptosis. Conversely, the pro‐apoptotic B cl2 family member, N oxa, is a critical initiator of mitotic cell death. Unexpectedly, the upstream components of the mitochondrial apoptosis pathway and the mitochondrial fission protein D rp1 contribute to mitotic adaption. Our results reveal crosstalk between the apoptosis and adaptation pathways during mitotic arrest.