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

J. Biol. Chem., Vol. 279, Issue 1, 788-795, January 2, 2004

This Article Full Text Full Text (PDF) All Versions of this Article: 279/1/788    most recent M308068200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted 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 Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Besnard-Guerin, C. Articles by Benarous, R. Search for Related Content PubMed PubMed Citation Articles by Besnard-Guerin, C. Articles by Benarous, R. Social Bookmarking                      What's this?

HIV-1 Vpu Sequesters -Transducin Repeat-containing Protein (TrCP) in the Cytoplasm and Provokes the Accumulation of -Catenin and Other SCF^TrCP Substrates^*

Corinne Besnard-Guerin, Nadia Belaïdouni, Irina Lassot¶, Emmanuel Segeral||, Aude Jobart, Christelle Marchal, and Richard Benarous**

From the Institut Cochin, Department of Infectious Diseases, INSERM U567, CNRS UMR 8104, Université R. Descartes Paris V, 27 Rue du Faubourg St. Jacques, 75014 Paris, France

The human immunodeficiency virus type 1 Vpu protein acts as an adaptor for the proteasomal degradation of CD4 by recruiting CD4 and -transducin repeat-containing protein (TrCP), the receptor component of the multisubunit SCF-TrCP E3 ubiquitin ligase complex. We showed that the expression of a Vpu-green fluorescent fusion protein prevented the proteosomal degradation of TrCP substrates such as -catenin, IB, and ATF4, which are normally directly targeted to the proteasome for degradation. -Catenin was translocated into the nucleus, whereas the tumor necrosis factor-induced nuclear translocation of NFB was impaired. -Catenin was also up-regulated in cells producing Vpu+ human immunodeficiency virus type 1 but not in cells producing Vpu-deficient viruses. The overexpression of ATF4 also provoked accumulation of -catenin, but to a lower level than that resulting from the expression of Vpu. Finally, the expression of Vpu induces the exclusion of TrCP from the nucleus. These data suggest that Vpu is a strong competitive inhibitor of TrCP that impairs the degradation of SCF^TrCP substrates as long as Vpu has an intact phosphorylation motif and can bind to TrCP.

Received for publication, July 24, 2003 , and in revised form, October 1, 2003.

^* This work was supported in part by grants from the Agence Nationale de Recherches sur le Sida, SIDACTION, the French Ministry of Research and Industry, Association pour la Recherche sur le Cancer, and Ligue Nationale Contre le Cancer. 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.

Supported by Sidaction.

^¶ Supported by La Ligue Nationale Contre le cancer.

^|| Supported by Association pour la Recherche sur le Cancer.

Supported by INSERM. To whom correspondence may be addressed. Tel.: 33-1-40-51-65-77; Fax: 33-1-40-51-65-70; E-mail: besnardguerin{at}cochin.inserm.fr.

^** To whom correspondence may be addressed. Tel.: 33-1-40-51-65-71; Fax: 33-1-40-51-65-70; E-mail: benarous{at}cochin.inserm.fr.

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

This article has been cited by other articles:

				N. van Buuren, B. Couturier, Y. Xiong, and M. Barry Ectromelia Virus Encodes a Novel Family of F-Box Proteins That Interact with the SCF Complex J. Virol., October 15, 2008; 82(20): 9917 - 9927. [Abstract] [Full Text] [PDF]

				Y.-J. Jin, C. Y. Cai, X. Zhang, and S. J. Burakoff Lysine 144, a Ubiquitin Attachment Site in HIV-1 Nef, Is Required for Nef-Mediated CD4 Down-Regulation J. Immunol., June 15, 2008; 180(12): 7878 - 7886. [Abstract] [Full Text] [PDF]

				A. Salim and L. Ratner Modulation of {beta}-Catenin and E-Cadherin Interaction by Vpu Increases Human Immunodeficiency Virus Type 1 Particle Release J. Virol., April 15, 2008; 82(8): 3932 - 3938. [Abstract] [Full Text] [PDF]

				K. H. Richards and P. R. Clapham Effects of vpu start-codon mutations on human immunodeficiency virus type 1 replication in macrophages J. Gen. Virol., October 1, 2007; 88(10): 2780 - 2792. [Abstract] [Full Text] [PDF]

				P. van Kerkhof, J. Putters, and G. J. Strous The Ubiquitin Ligase SCF(betaTrCP) Regulates the Degradation of the Growth Hormone Receptor J. Biol. Chem., July 13, 2007; 282(28): 20475 - 20483. [Abstract] [Full Text] [PDF]

				M. Tomita, A. Kikuchi, T. Akiyama, Y. Tanaka, and N. Mori Human T-Cell Leukemia Virus Type 1 Tax Dysregulates {beta}-Catenin Signaling J. Virol., November 1, 2006; 80(21): 10497 - 10505. [Abstract] [Full Text] [PDF]

				M. Barry and K. Fruh Viral Modulators of Cullin RING Ubiquitin Ligases: Culling the Host Defense Sci. Signal., May 16, 2006; 2006(335): pe21 - pe21. [Abstract] [Full Text] [PDF]

				S. Megy, G. Bertho, J. Gharbi-Benarous, N. Evrard-Todeschi, G. Coadou, E. Segeral, C. Iehle, E. Quemeneur, R. Benarous, and J.-P. Girault STD and TRNOESY NMR Studies on the Conformation of the Oncogenic Protein {beta}-Catenin Containing the Phosphorylated Motif DpSGXXpS Bound to the {beta}-TrCP Protein J. Biol. Chem., August 12, 2005; 280(32): 29107 - 29116. [Abstract] [Full Text] [PDF]

				Y. Kanemori, K. Uto, and N. Sagata {beta}-TrCP recognizes a previously undescribed nonphosphorylated destruction motif in Cdc25A and Cdc25B phosphatases PNAS, May 3, 2005; 102(18): 6279 - 6284. [Abstract] [Full Text] [PDF]

				A. Street, A. Macdonald, C. McCormick, and M. Harris Hepatitis C Virus NS5A-Mediated Activation of Phosphoinositide 3-Kinase Results in Stabilization of Cellular {beta}-Catenin and Stimulation of {beta}-Catenin-Responsive Transcription J. Virol., April 15, 2005; 79(8): 5006 - 5016. [Abstract] [Full Text] [PDF]

				M. Derrien, N. Pizzato, G. Dolcini, E. Menu, G. Chaouat, F. Lenfant, F. Barre-Sinoussi, and P. L. Bouteiller Human immunodeficiency virus 1 downregulates cell surface expression of the non-classical major histocompatibility class I molecule HLA-G1 J. Gen. Virol., July 1, 2004; 85(7): 1945 - 1954. [Abstract] [Full Text] [PDF]

				W. W. Henderson, R. Ruhl, P. Lewis, M. Bentley, J. A. Nelson, and A. V. Moses Human Immunodeficiency Virus (HIV) Type 1 Vpu Induces the Expression of CD40 in Endothelial Cells and Regulates HIV-Induced Adhesion of B-Lymphoma Cells J. Virol., May 1, 2004; 78(9): 4408 - 4420. [Abstract] [Full Text] [PDF]