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Necroptosis as a Novel Facet of Mitotic Catastrophe.


ABSTRACT: Mitotic catastrophe is a defensive mechanism that promotes elimination of cells with aberrant mitosis by triggering the cell-death pathways and/or cellular senescence. Nowadays, it is known that apoptosis, autophagic cell death, and necrosis could be consequences of mitotic catastrophe. Here, we demonstrate the ability of a DNA-damaging agent, doxorubicin, at 600 nM concentration to stimulate mitotic catastrophe. We observe that the inhibition of caspase activity leads to accumulation of cells with mitotic catastrophe hallmarks in which RIP1-dependent necroptotic cell death is triggered. The suppression of autophagy by a chemical inhibitor or ATG13 knockout upregulates RIP1 phosphorylation and promotes necroptotic cell death. Thus, in certain conditions mitotic catastrophe, in addition to apoptosis and autophagy, can precede necroptosis.

SUBMITTER: Egorshina AY 

PROVIDER: S-EPMC8998610 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature

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Necroptosis as a Novel Facet of Mitotic Catastrophe.

Egorshina Aleksandra Yu AY   Zamaraev Alexey V AV   Kaminskyy Vitaliy O VO   Radygina Tatiana V TV   Zhivotovsky Boris B   Kopeina Gelina S GS  

International journal of molecular sciences 20220329 7


Mitotic catastrophe is a defensive mechanism that promotes elimination of cells with aberrant mitosis by triggering the cell-death pathways and/or cellular senescence. Nowadays, it is known that apoptosis, autophagic cell death, and necrosis could be consequences of mitotic catastrophe. Here, we demonstrate the ability of a DNA-damaging agent, doxorubicin, at 600 nM concentration to stimulate mitotic catastrophe. We observe that the inhibition of caspase activity leads to accumulation of cells w  ...[more]

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