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Updated: Oct 3, 2026

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

The protein kinase PKB/Akt regulates cell survival and apoptosis by inhibiting Bax conformational change

H Yamaguchi1, H G Wang

  • 1Drug Discovery Program, H Lee Moffitt Cancer Center and Research Institute, Department of Interdisciplinary Oncology, University of South Florida College of Medicine, 12902 Magnolia Drive, Tampa, FL 33612, USA.

Oncogene
|December 26, 2001
PubMed

Insights

The serine-threonine kinase Akt prevents apoptosis by inhibiting the pro-apoptotic protein Bax. Akt blocks Bax conformational changes and mitochondrial translocation, thus protecting cells from programmed cell death.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • The serine-threonine kinase Akt is a key regulator of cell survival.
  • Akt mediates anti-apoptotic effects through various downstream targets.
  • Understanding Akt's precise mechanisms in preventing apoptosis is crucial.

Purpose of the Study:

  • To investigate the role of Akt in regulating the pro-apoptotic protein Bax.
  • To elucidate the pre-mitochondrial mechanisms by which Akt inhibits apoptosis.

Main Methods:

  • Utilized pre-B hematopoietic cells (FL5.12) and Hela cells.
  • Investigated effects of interleukin-3 (IL-3) withdrawal and methyl methanesulphonate treatment.
  • Examined protein conformational changes, mitochondrial translocation (using GFP-Bax), mitochondrial inner membrane potential (DeltaPsi(m)), and caspase-3 activation.
  • Inhibited PI-3 kinase and MAPK kinase pathways.

Main Results:

  • Akt inhibits Bax conformational change and its translocation to mitochondria.
  • This inhibition prevents mitochondrial inner membrane potential disruption, caspase-3 activation, and apoptosis.
  • PI-3 kinase inhibition, but not MAPK kinase inhibition, promotes Bax conformational change.
  • Akt overexpression suppresses GFP-Bax relocalization and apoptosis induced by DNA damage.
  • Akt does not prevent apoptosis induced by a constitutively active Bax mutant (GFP-Bax (DeltaS184)).

Conclusions:

  • Akt exerts anti-apoptotic effects at a pre-mitochondrial stage.
  • Akt's mechanism involves inhibiting Bax conformational change and its redistribution to mitochondrial membranes.

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