JCB logo
PeproTech: Cell Culture Supplements
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published online 22 March 2004. doi:10.1083/jcb.200309013
The Rockefeller University Press, 0021-9525 $8.00
JCB, Volume 164, Number 7, 1021-1032
This Article
Right arrow Full Text
Right arrow Full Text (PDF, 6066K)
Right arrow PPT slides of all figures
Right arrow Supplemental Material Index
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JCB
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Schinzel, A.
Right arrow Articles by Borner, C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Schinzel, A.
Right arrow Articles by Borner, C.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Facebook   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?

Article

Conformational control of Bax localization and apoptotic activity by Pro168



Anna Schinzel1,2, Thomas Kaufmann1,2, Martin Schuler3, Jorge Martinalbo1, David Grubb1, and Christoph Borner1

1 Institute of Molecular Medicine and Cell Research, Center for Biochemistry and Molecular Cell Research, Albert-Ludwigs-University Freiburg, D-79104 Freiburg, Germany
2 Institute of Biochemistry, University of Fribourg, CH-1700 Fribourg, Switzerland
3 Department of Medicine III, Johannes Gutenberg University, D-55101 Mainz, Germany

Address correspondence to C. Borner, Institute of Molecular Medicine and Cell Research, Center for Biochemistry and Molecular Cell Research, Albert-Ludwigs-University Freiburg, Stefan-Meier Strasse 17, D-79104 Freiburg, Germany. Tel.: 49-761-203-9618. Fax: 49-761-203-9620. email: borner{at}ukl.uni-freiburg.de

In healthy cells, Bax resides inactive in the cytosol because its COOH-terminal transmembrane region (TMB) is tucked into a hydrophobic pocket. During apoptosis, Bax undergoes a conformational change involving NH2-terminal exposure and translocates to mitochondria to release apoptogenic factors. How this process is regulated remains unknown. We show that the TMB of Bax is both necessary and sufficient for mitochondrial targeting. However, its availability for targeting depends on Pro168 located within the preceding loop region. Pro168 mutants of Bax lack apoptotic activity, cannot rescue the apoptosis-resistant phenotype of Bax/Bak double knockout cells, and are retained in the cytosol even in response to apoptotic stimuli. Moreover, the mutants have their NH2 termini exposed. We propose that Pro168 links the NH2 and the COOH terminus of Bax and is required for COOH-terminal release and mitochondrial targeting once this link is broken.

Key Words: apoptosis; Bcl-2 family; NH2-terminal exposure; mitochondria; targeting

The online version of this article contains supplemental material.

A. Schinzel's present address is Howard Hughes Medical Institute, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115.

Abbreviations used in this paper: ART, apoptosis-regulating targeting domain; IVTT, in vitro transcription/translation; MEF, mouse embryo fibroblast; MOM, mitochondrial outer membrane; PI, propidium iodide; PPIase, prolyl cis/trans isomerase; TMB, transmembrane region.


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Facebook Facebook   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?


This article has been cited by other articles:



  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents