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Phosphorylation of the proapoptotic BH3-only protein bid primes mitochondria for apoptosis during mitotic arrest

Pengbo Wang1, Jennefer Lindsay1, Thomas W Owens1

  • 1Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, UK.

Cell Reports
|April 29, 2014
PubMed

Insights

Mitotic slippage triggers apoptosis via phosphorylated Bid protein. This mechanism, crucial for normal cell death, may be bypassed in cancer cells.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Cancer Research

Background:

  • Mitosis is a critical cell division stage prone to errors.
  • Inaccurate mitosis can cause aneuploidy and cancer.
  • Delayed mitotic exit normally triggers apoptosis, but the mechanism is unclear.

Purpose of the Study:

  • To elucidate the mechanism by which delayed mitotic exit activates apoptosis.
  • To identify key molecular players regulating apoptosis during mitotic failure.

Main Methods:

  • Investigated the role of the BH3-only protein Bid in apoptosis.
  • Utilized mutant Bid proteins (non-phosphorylatable and BH3-domain mutants).
  • Examined Bid phosphorylation status during the cell cycle, specifically at serine 66.

Main Results:

  • Bid is phosphorylated at serine 66 upon mitotic entry.
  • This phosphorylation is lost during the metaphase-to-anaphase transition.
  • Cells with non-phosphorylatable or BH3-mutant Bid resisted apoptosis induced by mitotic arrest.

Conclusions:

  • Phosphorylated Bid acts as a critical regulator of apoptosis when mitotic exit is delayed.
  • Bid phosphorylation primes cells for mitochondrial apoptosis following mitotic errors.
  • Cancer cells may evade this apoptotic pathway through mechanisms like mitotic slippage.

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