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Star-PAP control of BIK expression and apoptosis is regulated by nuclear PIPKIα and PKCδ signaling

Weimin Li1, Rakesh S Laishram, Zhe Ji

  • 1Department of Pharmacology, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53706, USA.

Molecular Cell
|January 17, 2012
PubMed

Insights

DNA damage triggers BIK mRNA expression via nuclear Star-PAP, regulated by PKCδ and PI4,5P(2) signaling. This pathway controls apoptosis initiation, distinct from oxidative stress responses.

Area of Science:

  • Molecular Biology
  • Cellular Signaling
  • Biochemistry

Background:

  • BIK protein initiates mitochondrial apoptosis.
  • BIK expression is induced by proapoptotic signals like DNA damage.

Purpose of the Study:

  • To elucidate the mechanism controlling BIK mRNA 3' end processing and expression after DNA damage.
  • To identify the key molecular players involved in this regulatory pathway.

Main Methods:

  • Investigated the role of nuclear poly(A) polymerase Star-PAP in BIK mRNA regulation.
  • Examined the involvement of Protein Kinase C delta (PKCδ) and phosphoinositide signaling (PI4,5P(2)).
  • Analyzed the interaction between PKCδ, Star-PAP, and PIPKIα.

Main Results:

  • DNA damage induces PKCδ association with the Star-PAP complex, essential for BIK expression.
  • PKCδ interacts with PIPKIα, which generates PI4,5P(2), stimulating PKCδ activity and Star-PAP interaction.
  • Specific features in the BIK 3' UTR confer Star-PAP specificity, potentially inhibiting canonical polyadenylation.

Conclusions:

  • A nuclear signaling nexus involving PIPKIα, PI4,5P(2), and PKCδ regulates Star-PAP-mediated BIK expression and apoptosis.
  • This pathway demonstrates signal-specific mRNA 3' end processing, distinct from oxidative stress responses.

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