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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

Protein kinase C-delta phosphorylates Ebp1 and prevents its proteolytic degradation, enhancing cell survival

Zhixue Liu1, Xia Liu, Keiichi I Nakayama

  • 1Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia 30322, USA.

Journal of Neurochemistry
|February 24, 2007
PubMed

Insights

Protein kinase C (PKC)-delta phosphorylates ErbB3-binding protein (Ebp1), preventing its degradation by caspase 3 during apoptosis. This phosphorylation is crucial for cell survival, highlighting a novel anti-apoptotic mechanism.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • ErbB3-binding protein (Ebp1) is known to promote cell survival by inhibiting DNA fragmentation.
  • Ebp1 interacts with nuclear Akt, a complex mediated by Ebp1 phosphorylation by protein kinase C (PKC)-delta.

Purpose of the Study:

  • To investigate the role of Ebp1 as a substrate for caspase 3 during programmed cell death.
  • To elucidate the protective mechanism of PKC-delta phosphorylation on Ebp1 against apoptotic degradation.

Main Methods:

  • In vitro assays using cell-free apoptotic solutions.
  • Comparison of Ebp1 cleavage in PKC-delta-deficient cells versus wild-type cells.
  • Site-directed mutagenesis to analyze specific cleavage sites (D53, D196) and phosphorylation site (S360) of Ebp1.
  • Assessment of apoptosis in cells expressing wild-type and mutant Ebp1.

Main Results:

  • Ebp1 is degraded by active caspase 3 during apoptosis.
  • PKC-delta phosphorylation protects Ebp1 from caspase 3-mediated cleavage.
  • Ebp1 translated from the first ATG start codon is resistant to cleavage, while isoforms from the second and third ATG are degraded.
  • PKC phosphorylation at S360 inhibits Ebp1 cleavage by caspase 3.
  • Cleavage at D196 is a prerequisite for degradation at D53.
  • A D196A mutant of Ebp1 significantly protects cells from apoptosis.

Conclusions:

  • PKC-delta antagonizes apoptosis by phosphorylating Ebp1, thereby protecting it from caspase 3-induced degradation.
  • Ebp1 cleavage sites and isoforms play critical roles in regulating its susceptibility to apoptotic degradation.
  • The findings reveal a novel pathway where PKC-delta-mediated phosphorylation of Ebp1 is essential for cellular resistance to apoptosis.

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