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

J. Biol. Chem., Vol. 279, Issue 14, 13469-13477, April 2, 2004

This Article Full Text Full Text (PDF) All Versions of this Article: 279/14/13469    most recent M305250200v1 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 Sorokina, E. M. Articles by Tsygankov, A. Y. Search for Related Content PubMed PubMed Citation Articles by Sorokina, E. M. Articles by Tsygankov, A. Y. Social Bookmarking                      What's this?

Molecular Mechanisms of the Effect of Herpesvirus saimiri Protein StpC on the Signaling Pathway Leading to NF-B Activation^*

Elena M. Sorokina, Joseph J. Merlo, Jr., and Alexander Y. Tsygankov¶

From the Department of Microbiology and Immunology, Temple University School of Medicine, Philadelphia, Pennsylvania 19140

Herpesvirus saimiri (Saimiriine herpesvirus-2) causes lethal T lymphoproliferative diseases in the susceptible species and transforms T lymphocytes to continuous growth in vitro. H. saimiri-induced transformation of T cells is becoming an important experimental tool of biomedical research. Two proteins of H. saimiri subgroup C, Tip and StpC, are essential for T cell transformation by this virus. It has been shown previously that StpC transforms fibroblasts, activates NF-B, and binds to tumor necrosis factor (TNF)-receptor-associated factor (TRAF) proteins, but the molecular mechanism of its action remains insufficiently understood. This study further characterized the effect of StpC on NF-B. First, StpC activates NF-B via the consensus pathway involving activation of I-B kinase and subsequent phosphorylation and degradation of I-B in both T lymphoid and epithelial cells. Second, triggering of this pathway by StpC in both T lymphoid and epithelial cells is dependent on the presence of functional NF-B-inducing kinase (NIK). Third, StpC physically interacts with TRAF in epithelial cells, and the effect of StpC on NF-B activity in these cells requires the presence of functional TRAF. Finally the effect of StpC is completely independent of TNF-, a well described stimulus of NF-B activity. Moreover it appears that StpC uncouples stimulation of NF-B activity from TNF- stimulation. Overall these results argue that the effect of StpC on NF-B is similar to the effects of other viral proteins, "usurping" the TRAF/NIK/I-B kinase pathway, and reinforce the notion that the role of StpC in cell transformation by H. saimiri may be mediated by signaling that results in NF-B activation.

Received for publication, May 19, 2003 , and in revised form, December 31, 2003.

^* This work was supported by American Cancer Society Grant RPG-00-105-MBC (to A. Y. T.). 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.

Present address: Fox Chase Cancer Center, 7701 Burholme Ave., Philadelphia, PA 19111.

Present address: Vitagen, Inc., 3344 N. Torrey Pines Ct., La Jolla, CA 92037.

^¶ To whom correspondence should be addressed: Dept. of Microbiology & Immunology, Temple University School of Medicine, 3400 N. Broad St., Philadelphia, PA 19140. Tel.: 215-707-1745; Fax: 215-707-5205; E-mail: alexander.tsygankov{at}temple.edu.

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

This article has been cited by other articles:

				T. Suzuki, T. Shimizu, H.-P. Yu, Y.-C. Hsieh, M. A. Choudhry, K. I. Bland, and I. H. Chaudry Estrogen receptor-{alpha} predominantly mediates the salutary effects of 17beta-estradiol on splenic macrophages following trauma-hemorrhage Am J Physiol Cell Physiol, September 1, 2007; 293(3): C978 - C984. [Abstract] [Full Text] [PDF]

				T. Suzuki, T. Shimizu, H.-P. Yu, Y.-C. Hsieh, M. A. Choudhry, and I. H. Chaudry Salutary effects of 17beta-estradiol on T-cell signaling and cytokine production after trauma-hemorrhage are mediated primarily via estrogen receptor-{alpha} Am J Physiol Cell Physiol, June 1, 2007; 292(6): C2103 - C2111. [Abstract] [Full Text] [PDF]

				E. Heck, U. Friedrich, M. U. Gack, D. Lengenfelder, M. Schmidt, I. Muller-Fleckenstein, B. Fleckenstein, A. Ensser, and B. Biesinger Growth transformation of human T cells by herpesvirus saimiri requires multiple tip-lck interaction motifs. J. Virol., October 1, 2006; 80(20): 9934 - 9942. [Abstract] [Full Text] [PDF]

				M. M. Brinkmann and T. F. Schulz Regulation of intracellular signalling by the terminal membrane proteins of members of the Gammaherpesvirinae. J. Gen. Virol., May 1, 2006; 87(Pt 5): 1047 - 1074. [Abstract] [Full Text] [PDF]

				J.-C. Albrecht, I. Muller-Fleckenstein, M. Schmidt, B. Fleckenstein, and B. Biesinger Tyrosine Phosphorylation of the Tio Oncoprotein Is Essential for Transformation of Primary Human T Cells J. Virol., August 15, 2005; 79(16): 10507 - 10513. [Abstract] [Full Text] [PDF]