Identification of a novel protein kinase Cδ-Smac complex that dissociates during paclitaxel-induced cell death.
Author
Summary, in English
Protein kinase C (PKC) δ is a regulator of apoptosis with both pro- and anti-apoptotic effects. The mechanistic basis for the discrepant effects is not completely understood. Here we show that Smac interacts with PKCδ. The interaction depends on the N-terminus of Smac and is disrupted upon treatment with paclitaxel. This is associated with release of Smac into the cytosol. Activation of PKCδ rescues the interaction during paclitaxel exposure and suppresses the paclitaxel-mediated cell death. However, under these conditions the complex is mainly found in the cytosol suggesting that cytosolic Smac can be bound by PKCδ when PKC is activated. The data unravel a previously unrecognized interaction and suggest that PKCδ by associating with Smac may prevent its apoptotic effects. STRUCTURED SUMMARY OF PROTEIN INTERACTIONS: PKC deltaphysically interacts with SMAC by anti bait coimmunoprecipitation (View Interaction: 1, 2, 3, 4) XIAPphysically interacts with SMAC by anti tag coimmunoprecipitation(View interaction).
Department/s
- Department of Translational Medicine
- BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation
Publishing year
2012
Language
English
Pages
1166-1172
Publication/Series
FEBS Letters
Volume
586
Issue
8
Links
Document type
Journal article
Publisher
Wiley-Blackwell
Topic
- Biological Sciences
Keywords
- Smac
- Protein kinase C
- Apoptosis
- Cell death
- Paclitaxel
- XIAP
Status
Published
ISBN/ISSN/Other
- ISSN: 1873-3468