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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

14-3-3 inhibits Bad-induced cell death through interaction with serine-136

S C Masters1, H Yang, S R Datta

  • 1Graduate Program in Molecular and Systems Pharmacology, Emory University School of Medicine, Atlanta, Georgia, USA.

Molecular Pharmacology
|November 28, 2001
PubMed

Insights

14-3-3 proteins regulate cell death by binding to the proapoptotic protein Bad. Phosphorylation at serine 136 is critical for this interaction, while serine 112 appears dispensable for 14-3-3 binding and Bad function.

Area of Science:

  • Cellular Biology
  • Molecular Biology
  • Biochemistry

Background:

  • 14-3-3 proteins are key regulators of cell signaling pathways.
  • Dysregulated apoptosis is implicated in various diseases.
  • The proapoptotic protein Bad is a target of 14-3-3 proteins.

Purpose of the Study:

  • To elucidate the role of specific phosphorylation sites on Bad in mediating 14-3-3 binding.
  • To understand the contribution of these sites to the inhibition of Bad-induced apoptosis.

Main Methods:

  • In vitro binding assays.
  • Yeast and mammalian cell-based interaction studies.
  • Site-directed mutagenesis of Bad phosphorylation sites (S112 and S136).

Main Results:

  • 14-3-3/Bad interaction is dependent on phosphorylated serine 136 (S136) of Bad.
  • Mutation of S112 did not affect 14-3-3 binding to Bad.
  • 14-3-3 effectively abrogated cell death induced by wild-type and S112A Bad, but not S136A Bad.

Conclusions:

  • Phosphorylation of S136 is essential for 14-3-3 to inhibit Bad's proapoptotic activity.
  • S112 phosphorylation may regulate a separate, 14-3-3-independent pathway.
  • These findings highlight the critical role of S136 phosphorylation in 14-3-3-mediated apoptosis regulation.

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