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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 is a pro-survival factor prior to activation of its pro-apoptotic function

So Young Seo1, Ying-Bei Chen, Iva Ivanovska

  • 1W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD21205, USA.

The Journal of Biological Chemistry
|July 3, 2004
PubMed

Insights

The BAD protein, a member of the BCL-2 family, acts as a pro-survival factor in healthy cells before promoting cell death. Its function is regulated by alternative splicing and caspase cleavage, influencing cell fate.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Apoptosis Research

Background:

  • The BCL-2 family protein BAD is known for its pro-apoptotic function.
  • Endogenous and overexpressed BAD(L) (long isoform) can inhibit cell death in various cell types, including neurons.

Purpose of the Study:

  • To investigate the dual role of BAD protein as both a pro-survival and pro-death factor.
  • To elucidate the regulatory mechanisms governing BAD's conversion from a survival to a death factor.

Main Methods:

  • Analysis of endogenous and overexpressed BAD(L) in different cell types.
  • Investigation of alternative splicing producing BAD(S) (short isoform).
  • Study of caspase cleavage sites and their conservation between human and murine BAD.

Main Results:

  • BAD(L) exhibits pro-survival activity in healthy cells.
  • Alternative splicing to BAD(S) and caspase cleavage convert BAD(L) into a pro-death fragment.
  • Differential conservation of caspase cleavage sites between human and murine BAD explains species-specific death promotion.
  • N-terminal truncation alone is insufficient to activate BAD's pro-death activity.

Conclusions:

  • BAD functions as a pro-survival factor in healthy cells before its role in apoptosis.
  • The N terminus of BAD acts as a regulatory domain, not solely an anti-death domain.
  • Mechanisms like alternative splicing and caspase cleavage finely tune BAD's role in cell death pathways.

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