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Assessment of Mitochondrial Functions and Cell Viability in Renal Cells Overexpressing Protein Kinase C Isozymes
Published on: January 7, 2013
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
Summary
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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