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

UNSPECIFIED (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
Contributors:
ContributionContributors NameEmailPitt UsernameORCID
EditorSong, LibingUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
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: 08 Jan 2019 16:55
URI: http://d-scholarship.pitt.edu/id/eprint/12703

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