Caspase-independent mitotic death (CIMD)

Cell Cycle
Katsumi Kitagawa, Yohei Niikura

Abstract

The spindle checkpoint, which monitors kinetochore-microtubule attachment, is required for high fidelity of chromosome transmission. A failure in this mechanism causes aneuploidy, thereby promoting progression to tumorigenesis. However, the cell death mechanism that prevents the aneuploidy caused by failure of the spindle checkpoint is yet unknown. We have recently identified a novel type of mitotic cell death, which we term caspase-independent mitotic death (CIMD). In BUB1-deficient (but not MAD2-deficient) cells, CIMD is induced by conditions that activate the spindle checkpoint (i.e., cold shock or treatment with nocodazole, paclitaxel or 17-AAG [17-allylaminogeldanamycin]). CIMD depends on p73, a homolog of p53, but not on p53. It also depends on the apoptosis-inducing factor (AIF) and endonuclease G (Endo G), which are effectors of caspase-independent cell death. When BUB1 is completely depleted, aneuploidy occurs instead of CIMD. We propose that CIMD can be the cell death mechanism that protects cells from aneuploidy by inducing the death of cells prone to substantial chromosome missegregation. Our study also shows that previous evaluations of the spindle checkpoint activity in mutant or cancer cells by monitoring mitotic...Continue Reading

Citations

Jan 9, 2010·Cell Death and Differentiation·Y NiikuraK Kitagawa
Dec 15, 2010·Cell Death and Differentiation·S-K LaiH-Y Li
Sep 8, 2009·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Annika JögiKarin Jirström
Apr 16, 2010·Canadian Journal of Physiology and Pharmacology·Yongqiang ChenSpencer B Gibson
Aug 2, 2012·Biochemistry Research International·Geun-Hyoung Ha, Eun-Kyoung Yim Breuer
Jun 8, 2013·Virology Journal·Alma Mariana Fuentes-GonzálezMarcela Lizano
Feb 8, 2011·PLoS Genetics·Greicy H GotoKatsumi Kitagawa
Jul 15, 2011·Clinical and Experimental Gastroenterology·Claire M PayneHarris Bernstein
Apr 18, 2009·Toxicology and Applied Pharmacology·Cecilia Eliana Hanzel, Sandra Viviana Verstraeten
Nov 21, 2008·ChemMedChem·Mar OrzáezEnrique Pérez-Payá
Mar 26, 2011·IUBMB Life·Laure DelavalléeSantos A Susin
Feb 22, 2012·Experimental Cell Research·Eleonora OttinaAndreas Villunger
Jun 6, 2009·International Review of Cell and Molecular Biology·Albrecht StenzingerMonika Wimmer

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