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Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death
09:18

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death

Published on: December 27, 2016

BAD detects coincidence of G2/M phase and growth factor deprivation to regulate apoptosis

Akiko Hashimoto1, Kenzo Hirose, Masamitsu Iino

  • 1Department of Pharmacology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan.

The Journal of Biological Chemistry
|May 20, 2005
PubMed

Insights

The protein BAD, crucial for apoptosis, detaches from 14-3-3zeta during the G2/M cell cycle phase. This dissociation, linked to Ser-128 phosphorylation, triggers apoptosis when growth factors are absent.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • The Bcl-2 family protein BAD promotes apoptosis.
  • BAD's interaction with 14-3-3zeta regulates its pro-apoptotic activity.

Purpose of the Study:

  • To investigate the cell cycle-dependent regulation of BAD.
  • To determine the role of BAD-14-3-3zeta interaction in apoptosis.

Main Methods:

  • Analysis of BAD and 14-3-3zeta interaction during the cell cycle.
  • Site-directed mutagenesis of BAD at Ser-128.
  • Assessment of apoptosis induction under growth factor deprivation.

Main Results:

  • BAD dissociates from 14-3-3zeta during the G2/M phase, dependent on Ser-128 phosphorylation.
  • A non-phosphorylatable S128A-BAD mutant remained bound to 14-3-3zeta throughout the cell cycle.
  • Growth factor deprivation induced apoptosis specifically at the G2/M phase in wild-type cells, but was delayed in S128A-BAD expressing cells.

Conclusions:

  • BAD's dissociation from 14-3-3zeta at G2/M is a key event for apoptosis.
  • The coincidence of G2/M phase and growth factor deprivation, mediated by BAD, triggers apoptosis.

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