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Restraint of apoptosis during mitosis through interdomain phosphorylation of caspase-2.

Publication ,  Journal Article
Andersen, JL; Johnson, CE; Freel, CD; Parrish, AB; Day, JL; Buchakjian, MR; Nutt, LK; Thompson, JW; Moseley, MA; Kornbluth, S
Published in: EMBO J
October 21, 2009

The apoptotic initiator caspase-2 has been implicated in oocyte death, in DNA damage- and heat shock-induced death, and in mitotic catastrophe. We show here that the mitosis-promoting kinase, cdk1-cyclin B1, suppresses apoptosis upstream of mitochondrial cytochrome c release by phosphorylating caspase-2 within an evolutionarily conserved sequence at Ser 340. Phosphorylation of this residue, situated in the caspase-2 interdomain, prevents caspase-2 activation. S340 was susceptible to phosphatase 1 dephosphorylation, and an interaction between phosphatase 1 and caspase-2 detected during interphase was lost in mitosis. Expression of S340A non-phosphorylatable caspase-2 abrogated mitotic suppression of caspase-2 and apoptosis in various settings, including oocytes induced to undergo cdk1-dependent maturation. Moreover, U2OS cells treated with nocodazole were found to undergo mitotic catastrophe more readily when endogenous caspase-2 was replaced with the S340A mutant to lift mitotic inhibition. These data demonstrate that for apoptotic stimuli transduced by caspase-2, cell death is prevented during mitosis through the inhibitory phosphorylation of caspase-2 and suggest that under conditions of mitotic arrest, cdk1-cyclin B1 activity must be overcome for apoptosis to occur.

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Published In

EMBO J

DOI

EISSN

1460-2075

Publication Date

October 21, 2009

Volume

28

Issue

20

Start / End Page

3216 / 3227

Location

England

Related Subject Headings

  • Xenopus
  • Serine
  • RNA, Small Interfering
  • Phosphorylation
  • Oocytes
  • Nocodazole
  • Mitosis
  • Lentivirus
  • Humans
  • Genetic Vectors
 

Citation

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Andersen, J. L., Johnson, C. E., Freel, C. D., Parrish, A. B., Day, J. L., Buchakjian, M. R., … Kornbluth, S. (2009). Restraint of apoptosis during mitosis through interdomain phosphorylation of caspase-2. EMBO J, 28(20), 3216–3227. https://doi.org/10.1038/emboj.2009.253
Andersen, Joshua L., Carrie E. Johnson, Christopher D. Freel, Amanda B. Parrish, Jennifer L. Day, Marisa R. Buchakjian, Leta K. Nutt, J Will Thompson, M Arthur Moseley, and Sally Kornbluth. “Restraint of apoptosis during mitosis through interdomain phosphorylation of caspase-2.EMBO J 28, no. 20 (October 21, 2009): 3216–27. https://doi.org/10.1038/emboj.2009.253.
Andersen JL, Johnson CE, Freel CD, Parrish AB, Day JL, Buchakjian MR, et al. Restraint of apoptosis during mitosis through interdomain phosphorylation of caspase-2. EMBO J. 2009 Oct 21;28(20):3216–27.
Andersen, Joshua L., et al. “Restraint of apoptosis during mitosis through interdomain phosphorylation of caspase-2.EMBO J, vol. 28, no. 20, Oct. 2009, pp. 3216–27. Pubmed, doi:10.1038/emboj.2009.253.
Andersen JL, Johnson CE, Freel CD, Parrish AB, Day JL, Buchakjian MR, Nutt LK, Thompson JW, Moseley MA, Kornbluth S. Restraint of apoptosis during mitosis through interdomain phosphorylation of caspase-2. EMBO J. 2009 Oct 21;28(20):3216–3227.

Published In

EMBO J

DOI

EISSN

1460-2075

Publication Date

October 21, 2009

Volume

28

Issue

20

Start / End Page

3216 / 3227

Location

England

Related Subject Headings

  • Xenopus
  • Serine
  • RNA, Small Interfering
  • Phosphorylation
  • Oocytes
  • Nocodazole
  • Mitosis
  • Lentivirus
  • Humans
  • Genetic Vectors