The Journal of Experimental Medicine
ELISpot, FluoroSpot and ELISA kits from Mabtech
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published 5 November 2001. doi:10.1084/jem.194.9.1299
This Article
Right arrow Full Text
Right arrow Full Text (PDF, 403K)
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 Akari, H.
Right arrow Articles by Strebel, K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Akari, H.
Right arrow Articles by Strebel, K.
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?
© Rockefeller University Press, 0022-1007/2001/11/1299/ $5.00
The Journal of Experimental Medicine, Volume 194, Number 9, November 5, 2001 1299-1312

Original Article

The Human Immunodeficiency Virus Type 1 Accessory Protein Vpu Induces Apoptosis by Suppressing the Nuclear Factor {kappa}B–dependent Expression of Antiapoptotic Factors

Hirofumi Akari1,2, Stephan Bour1, Sandra Kao1, Akio Adachi2 and Klaus Strebel1

1 Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892
2 Department of Virology, The University of Tokushima School of Medicine, Tokushima 770-8503, Japan

Address correspondence to Klaus Strebel, NIH/NIAID, 4/312 4 Center Dr., MSC 0460 Bethesda, MD 20892-0460. Phone: 301-496-3132; Fax: 301-402-0226; E-mail: kstrebel{at}nih.gov

Human immunodeficiency virus (HIV) type 1 Vpu is an integral membrane protein with a unique affinity for ßTrCP (TrCP), a key member of the SkpI-Cullin-F-box E3 ubiquitin ligase complex that is involved in the regulated degradation of cellular proteins, including I{kappa}B. Remarkably, Vpu is resistant to TrCP-mediated degradation and competitively inhibits TrCP-dependent degradation of I{kappa}B, resulting in the suppression of nuclear factor (NF)-{kappa}B activity in Vpu-expressing cells. We now report that Vpu, through its interaction with TrCP, potently contributes to the induction of apoptosis in HIV-infected T cells. Vpu-induced apoptosis is specific and independent of other viral proteins. Mutation of a TrCP-binding motif in Vpu abolishes its apoptogenic property, demonstrating a close correlation between this property of Vpu and its ability to inhibit NF-{kappa}B activity. The involvement of NF-{kappa}B in Vpu-induced apoptosis is further supported by the finding that the levels of antiapoptotic factors Bcl-xL, A1/Bfl-1, and TNF receptor-associated factor (TRAF)1, all of which are expressed in an NF-{kappa}B–dependent manner, are reduced and, at the same time, levels of active caspase-3 are elevated. Thus, Vpu induces apoptosis through activation of the caspase pathway by way of inhibiting the NF-{kappa}B–dependent expression of antiapoptotic genes.

Key Words: TrCP • caspase • TNF-{alpha} • Bcl-xL • TRAF1


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