The Journal of Experimental Medicine
Torrey Pines Biolabs
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published online 3 January 2006 doi:10.1084/jem.20050433
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 203, Number 1, 189-201
This Article
Right arrow Full Text
Right arrow Full Text (PDF, 4481K)
Right arrow PPT slides of all figures
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 JEM
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 Sionov, R. V.
Right arrow Articles by Yefenof, E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Sionov, R. V.
Right arrow Articles by Yefenof, E.
Right arrowPubmed/NCBI databases
*Gene*GEO Profiles
*HomoloGene*UniGene
*Compound via MeSH
*Substance via MeSH
Hazardous Substances DB
*DEXAMETHASONE
Medline Plus Health Information
*Steroids
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

ARTICLE

 Role of mitochondrial glucocorticoid receptor in glucocorticoid-induced apoptosis

Ronit Vogt Sionov1, Orly Cohen1, Shlomit Kfir1, Yael Zilberman2, and Eitan Yefenof1

1 The Lautenberg Center for General and Tumor Immunology, The Hebrew University-Hadassah Medical School and 2 Department of Pharmacology, Faculty of Dental Medicine Founded by the Alpha-Omega Fraternity, 91120 Jerusalem, Israel

CORRESPONDENCE Eitan Yefenof: yefenof{at}cc.huji.ac.il

The mechanisms by which glucocorticoid receptor (GR) mediates glucocorticoid (GC)-induced apoptosis are unknown. We studied the role of mitochondrial GR in this process. Dexamethasone induces GR translocation to the mitochondria in GC-sensitive, but not in GC-resistant, T cell lines. In contrast, nuclear GR translocation occurs in all cell types. Thymic epithelial cells, which cause apoptosis of the PD1.6 T cell line in a GR-dependent manner, induce GR translocation to the mitochondria, but not to the nucleus, suggesting a role for mitochondrial GR in eliciting apoptosis. This hypothesis is corroborated by the finding that a GR variant exclusively expressed in the mitochondria elicits apoptosis of several cancer cell lines. A putative mitochondrial localization signal was defined to amino acids 558–580 of human GR, which lies within the NH2-terminal part of the ligand-binding domain. Altogether, our data show that mitochondrial and nuclear translocations of GR are differentially regulated, and that mitochondrial GR translocation correlates with susceptibility to GC-induced apoptosis.

Abbreviations used: ALL, acute lymphoblastic leukemia; COX, cytochrome C oxidase; DBD, DNA-binding domain; Dex, dexamethasone; GC, glucocorticoid; GR, glucocorticoid receptor; GRE, glucocorticoid response element; hGR, human GR; LBD, ligand binding domain; mGR, membrane glucocorticoid receptor; MLS, mitochondrial localization signal; NLS, nuclear localization signal; PML, promyelocytic leukemia; TEC, thymic epithelial cell.


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 Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:



  Home | Help | Feedback | Subscriptions | Archive | Search
TABLE OF CONTENTS