Interaction of caveolin-1 with Ku70 inhibits Bax-mediated apoptosis

Zou, H and Volonte, D and Galbiati, F (2012) Interaction of caveolin-1 with Ku70 inhibits Bax-mediated apoptosis. PLoS ONE, 7 (6).

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Abstract

Caveolin-1, the structural protein component of caveolae, acts as a scaffolding protein that functionally regulates signaling molecules. We show that knockdown of caveolin-1 protein expression enhances chemotherapeutic drug-induced apoptosis and inhibits long-term survival of colon cancer cells. In vitro studies demonstrate that caveolin-1 is a novel Ku70-binding protein, as shown by the binding of the scaffolding domain of caveolin-1 (amino acids 82-101) to the caveolin-binding domain (CBD) of Ku70 (amino acids 471-478). Cell culture data show that caveolin-1 binds Ku70 after treatment with chemotherapeutic drugs. Mechanistically, we found that binding of caveolin-1 to Ku70 inhibits the chemotherapeutic drug-induced release of Bax from Ku70, activation of Bax, translocation of Bax to mitochondria and apoptosis. Potentiation of apoptosis by knockdown of caveolin-1 protein expression is greatly reduced in the absence of Bax expression. Finally, we found that overexpression of wild type Ku70, but not a mutant form of Ku70 that cannot bind to caveolin-1 (Ku70 Φ→A), limits the chemotherapeutic drug-induced Ku70/Bax dissociation and apoptosis. Thus, caveolin-1 acts as an anti-apoptotic protein in colon cancer cells by binding to Ku70 and inhibiting Bax-dependent cell death. © 2012 Zou et al.

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Details

Item Type:	Article
Status:	Published
Creators/Authors:	Creators Email Pitt Username ORCID Zou, H Volonte, D Galbiati, F feg5@pitt.edu FEG5
Contributors:	Contribution Contributors Name Email Pitt Username ORCID Editor Song, Libing UNSPECIFIED UNSPECIFIED UNSPECIFIED
Date:	20 June 2012
Date Type:	Publication
Journal or Publication Title:	PLoS ONE
Volume:	7
Number:	6
DOI or Unique Handle:	10.1371/journal.pone.0039379
Refereed:	Yes
PubMed ID:	22745744
Date Deposited:	11 Jul 2012 18:11
Last Modified:	05 Feb 2019 16:55
URI:	http://d-scholarship.pitt.edu/id/eprint/12703

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