Phosphorylation of XIAP by CDK1-cyclin-B1 controls mitotic cell death

Hou, Ying, Allan, Lindsey A. and Clarke, Paul R. (2017) Phosphorylation of XIAP by CDK1-cyclin-B1 controls mitotic cell death. Journal of Cell Science, 130 2: 502-511. doi:10.1242/jcs.192310

Author Hou, Ying
Allan, Lindsey A.
Clarke, Paul R.
Title Phosphorylation of XIAP by CDK1-cyclin-B1 controls mitotic cell death
Journal name Journal of Cell Science   Check publisher's open access policy
ISSN 1477-9137
Publication date 2017-01-01
Year available 2017
Sub-type Article (original research)
DOI 10.1242/jcs.192310
Open Access Status DOI
Volume 130
Issue 2
Start page 502
End page 511
Total pages 10
Place of publication Cambridge, United Kingdom
Publisher Company of Biologists
Language eng
Abstract Regulation of cell death is crucial for the response of cancer cells to drug treatments that cause arrest in mitosis, and is likely to be important for protection against chromosome instability in normal cells. Prolonged mitotic arrest can result in cell death by activation of caspases and the induction of apoptosis. Here, we show that Xlinked inhibitor of apoptosis (XIAP) plays a key role in the control of mitotic cell death. Ablation of XIAP expression sensitises cells to prolonged mitotic arrest caused by a microtubule poison. XIAP is stable during mitotic arrest, but its function is controlled through phosphorylation by the mitotic kinase CDK1-cyclin-B1 at S40. Mutation of S40 to a phosphomimetic residue (S40D) inhibits binding to activated effector caspases and abolishes the anti-apoptotic function of XIAP, whereas a non-phosphorylatable mutant (S40A) blocks apoptosis. By performing live-cell imaging, we show that phosphorylation of XIAP reduces the threshold for the onset of cell death in mitosis. This work illustrates that mitotic cell death is a form of apoptosis linked to the progression of mitosis through control by CDK1-cyclin-B1.
Keyword Apoptosis
Cell death
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID C275/A13424
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
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