HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 283, Issue 10, 6384-6392, March 7, 2008

This Article Full Text Full Text (PDF) All Versions of this Article: 283/10/6384    most recent M707762200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Germain, M. Articles by Duronio, V. Search for Related Content PubMed PubMed Citation Articles by Germain, M. Articles by Duronio, V. Social Bookmarking                      What's this?

MCL-1 Inhibits BAX in the Absence of MCL-1/BAX Interaction^*

From the Department of Medicine, University of British Columbia, and the Vancouver Coastal Health Research Institute, Jack Bell Research Centre, Vancouver, British Columbia V6H 3Z6, Canada

The BCL-2 family of proteins plays a major role in the control of apoptosis as the primary regulator of mitochondrial permeability. The pro-apoptotic BCL-2 homologues BAX and BAK are activated following the induction of apoptosis and induce cytochrome c release from mitochondria. A second class of BCL-2 homologues, the BH3-only proteins, is required for the activation of BAX and BAK. The activity of both BAX/BAK and BH3-only proteins is opposed by anti-apoptotic BCL-2 homologues such as BCL-2 and MCL-1. Here we show that anti-apoptotic MCL-1 inhibits the function of BAX downstream of its initial activation and translocation to mitochondria. Although MCL-1 interacted with BAK and inhibited its activation, the activity of MCL-1 against BAX was independent of an interaction between the two proteins. However, the anti-apoptotic function of MCL-1 required the presence of BAX. These results suggest that the pro-survival activity of MCL-1 proceeds via inhibition of BAX function at mitochondria, downstream of its activation and translocation to this organelle.

Received for publication, September 17, 2007 , and in revised form, December 14, 2007.

^* This work was supported in part by a grant from the Canadian Institutes of Health Research. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

² Supported by a summer student training grant from the Canadian Institutes of Health Research/Michael Smith Foundation for Health Research Training Program for Translational Research in Infectious Diseases.

³ Recipient of a Senior Scientist award from the Michael Smith Foundation for Health Research.

¹ To whom correspondence should be addressed: Neuroscience Research Institute, University of Ottawa, 451 Smyth Rd., Ottawa, Ontario K1H 8M5, Canada. Tel.: 613-562-5800, ext. 8459; E-mail: marc.germain{at}uottawa.ca.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				J. L. Wilsbacher, Q. Zhang, L. A. Tucker, R. D. Hubbard, G. S. Sheppard, N. Y. Bamaung, S. D. Fidanze, G. T. Wang, X. Hu, S. K. Davidsen, et al. Insulin-like Growth Factor-1 Receptor and ErbB Kinase Inhibitor Combinations Block Proliferation and Induce Apoptosis through Cyclin D1 Reduction and Bax Activation J. Biol. Chem., August 29, 2008; 283(35): 23721 - 23730. [Abstract] [Full Text] [PDF]

				O. Terrones, A. Etxebarria, A. Landajuela, O. Landeta, B. Antonsson, and G. Basanez BIM and tBID Are Not Mechanistically Equivalent When Assisting BAX to Permeabilize Bilayer Membranes J. Biol. Chem., March 21, 2008; 283(12): 7790 - 7803. [Abstract] [Full Text] [PDF]