Arnold Library

Quantitative proteomic analysis of myc-induced apoptosis: a direct role for Myc induction of the mitochondrial chloride ion channel, mtCLIC/CLIC4.

Shiio, Yuzuru and Suh, Kwang S and Lee, Hookeun and Yuspa, Stuart H and Eisenman, Robert N and Aebersold, Ruedi (2006) Quantitative proteomic analysis of myc-induced apoptosis: a direct role for Myc induction of the mitochondrial chloride ion channel, mtCLIC/CLIC4. The Journal of biological chemistry, 281 (5). pp. 2750-2576. ISSN 0021-9258

Full text not available from this repository.
Article URL: http://www.jbc.org/cgi/content/abstract/281/5/2750

Abstract

Myc is a key regulatory protein in higher eukaryotes controlling important cellular functions such as proliferation, differentiation, and apoptosis. Myc is profoundly involved in the genesis of many human and animal cancers, and the abrogation of Myc-induced apoptosis is a critical event in cancer progression. Because the mechanisms that mediate Myc-induced apoptosis are largely unknown, we analyzed protein expression during Myc-induced apoptosis using an isotope-coded affinity tag quantitative proteomics approach and identified that a proapoptotic mitochondrial chloride ion channel, mtCLIC/CLIC4, is induced by Myc. Myc binds to the mtCLIC gene promoter and activates its transcription. Suppression of mtCLIC expression by RNA interference inhibited Myc-induced apoptosis in response to different stress conditions and abolished the cooperative induction of apoptosis by Myc and Bax. We also found that Myc reduces the expression of Bcl-2 and Bcl-xL and that the apoptosis-inducing stimuli up-regulate Bax expression. These results suggest that up-regulation of mtCLIC, together with a reduction in Bcl-2 and Bcl-xL, sensitizes Myc-expressing cells to the proapoptotic action of Bax.

Item Type: Article
Additional Information: This article is freely available at the journal's website via the Article URL above.
DOI: 10.1074/jbc.M509349200
PubMed ID: 16316993
Grant Numbers: N01-HV-28179
Keywords or MeSH Headings: Apoptosis/genetics; Apoptosis Regulatory Proteins/genetics; Chloride Channels/genetics; Gene Expression Regulation; Humans; Mitochondrial Proteins/genetics; Proteomics; Proto-Oncogene Proteins c-myc/physiology; RNA, Small Interfering/pharmacology; Stress, Physiological/genetics; bcl-2-Associated X Protein/genetics/physiology;
Subjects: Molecules > Proteins > Transcription factors
Research Methodologies > Proteomics
Cellular and Organismal Processes > Cell Physiology > Cell death
Molecules > Genes > Oncogenes
Depositing User: Library Staff
Date Deposited: 17 Dec 2008 19:24
Last Modified: 10 May 2010 22:09
URI: http://authors.fhcrc.org/id/eprint/210

Repository Administrators Only

View Item View Item
Fred Hutchinson Cancer Research Center
1100 Fairview Ave. N. PO Box 19024
Seattle, WA 98109

a 501(c)(3) nonprofit organization.

© Terms of Use & Privacy Policy