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p23/Tmp21 associates with protein kinase Cdelta (PKCdelta) and modulates its apoptotic function

HongBin Wang1, Liqing Xiao, Marcelo G Kazanietz

  • 1Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6160, USA. hongbin@mail.med.upenn.edu

The Journal of Biological Chemistry
|April 2, 2011
PubMed

Insights

Protein kinase C delta (PKCδ) interacts with p23, a protein that anchors it away from the plasma membrane. Silencing p23 enhances PKCδ-driven apoptosis in prostate cancer cells.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • C1 domains in protein kinase C (PKC) are known to bind lipids like diacylglycerol.
  • Emerging evidence suggests C1 domains also interact with cellular proteins, including the Golgi/endoplasmic reticulum protein p23 (Tmp21).
  • PKCδ is a kinase involved in apoptosis and cell cycle regulation.

Purpose of the Study:

  • To investigate the association between PKCδ and p23.
  • To determine the functional significance of the PKCδ-p23 interaction.
  • To explore the role of p23 in regulating PKCδ activity and localization.

Main Methods:

  • Yeast two-hybrid assay to identify protein interactions.
  • RNA interference (RNAi) to silence p23 expression in LNCaP prostate cancer cells.
  • Analysis of apoptosis, downstream effector activation (ROCK, JNK), and protein translocation.

Main Results:

  • The C1b domain of PKCδ directly associates with p23, with key residues Asp(245) and Met(266) identified.
  • Silencing p23 significantly enhanced PKCδ-dependent apoptosis and activation of ROCK and JNK upon stimulation.
  • p23 depletion led to increased translocation of PKCδ to the plasma membrane.
  • A PKCδ mutant unable to interact with p23 induced strong apoptosis.

Conclusions:

  • C1 domains exhibit dual functionality, engaging in both lipid and protein interactions.
  • p23 functions as an anchoring protein, retaining PKCδ in the perinuclear region.
  • This anchoring by p23 limits PKCδ availability for activation, thereby modulating cellular responses like apoptosis.

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