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

Weimin Li, Rakesh S. Laishram, Zhe Ji, Christy A. Barlow, Bin Tian, Richard A. Anderson*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

46 Scopus citations

Abstract

BIK protein is an initiator of mitochondrial apoptosis, and BIK expression is induced by proapoptotic signals, including DNA damage. Here, we demonstrate that 3' end processing and expression of BIKmRNA are controlled by the nuclear PI4,5P 2-regulated poly(A) polymerase Star-PAP downstream of DNA damage. Nuclear PKCδ is a key mediator ofapoptosis, and DNA damage stimulates PKCδ association with the Star-PAP complex where PKCδ is required for Star-PAP-dependent BIK expression. PKCδ binds the PI4,5P 2-generating enzyme PIPKIα, which is essential for PKCδ interaction with the Star-PAP complex, and PKCδ activity is directly stimulated by PI4,5P 2. Features in the BIK3' UTR uniquely define Star-PAP specificity and may block canonical PAP activity toward BIK mRNA. This reveals a nuclear phosphoinositide signaling nexus where PIPKIα, PI4,5P 2, and PKCδ regulate Star-PAP control of BIK expression and induction of apoptosis. This pathway is distinct from the Star-PAP-mediated oxidative stress pathway indicating signal-specific regulation of mRNA 3' end processing.

Original languageEnglish (US)
Pages (from-to)25-37
Number of pages13
JournalMolecular cell
Volume45
Issue number1
DOIs
StatePublished - Jan 13 2012

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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