Caspase-independent mitotic death

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The spindle checkpoint ensures proper chromosomal segregation by monitoring kinetochore-microtubule attachment. A failure of this checkpoint causes aneuploidy, which leads to tumorigenesis. The cell death that prevents the aneuploidy caused by failure of the spindle checkpoint is yet unknown. We have identified a novel type of mitotic cell death, which we term caspase-independent mitotic death (CIMD). When BUB1 but not MAD2 is depleted, CIMD is induced by conditions that activate the spindle checkpoint [e.g., cold shock or treatment with microtubule inhibitors or 17-AAG (17-allylaminogeldanamycin)]. CIMD depends on the apoptosis-inducing factor (AIF) and endonuclease G (Endo G), which are effectors of caspase-independent cell death. CIMD also depends on p73, a homologue of p53, but not on p53. When BUB1 is completely depleted, aneuploidy occurs instead of CIMD. Therefore, CIMD may be the programmed cell death that protects cells from aneuploidy by inducing the death of cells prone to substantial chromosome missegregation.

Idioma originalEnglish (US)
Título de la publicación alojadaEssentials of Apoptosis
Subtítulo de la publicación alojadaA Guide for Basic and Clinical Research
EditorialHumana Press
Número de páginas12
ISBN (versión digital)9781603273817
ISBN (versión impresa)9781603273800
EstadoPublished - 2009
Publicado de forma externa

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology


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