Activation of the STAT6 transcription factor in Jurkat T-cells by the herpesvirus saimiri Tip protein.
Herpesvirus saimiri (HVS), a T-lymphotropic monkey herpesvirus, induces fulminant T-cell lymphoma in non-natural primate hosts. In addition, it can immortalize human T-cells in vitro. HVS tyrosine kinase-interacting protein (Tip) is an essential viral gene required for T-cell transformation both in vitro and in vivo. In this study, we found that Tip interacts with the STAT6 transcription factor and induces phosphorylation of STAT6 in T-cells. The interaction with STAT6 requires the Tyr(127) residue and Lck-binding domain of Tip, which are indispensable for interleukin (IL)-2-independent T-cell transformation by HVS. It was also demonstrated that Tip induces nuclear translocation of STAT6, as well as activation of STAT6-dependent transcription in Jurkat T-cells. Interestingly, the phosphorylated STAT6 mainly colocalized with vesicles containing Tip within T-cells, but was barely detectable in the nucleus. However, nuclear translocation of phospho-STAT6 and transcriptional activation of STAT6 by IL-4 stimulation were not affected significantly in T-cells expressing Tip. Collectively, these findings suggest that the constitutive activation of STAT6 by Tip in T-cells may contribute to IL-2-independent T-cell transformation by HVS.
Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul, Republic of Korea.
Yuri
Y
Kim
Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul, Republic of Korea.
Eun-Kyung
EK
Kwon
Department of Physiology, Seoul National University College of Medicine, Seoul, Republic of Korea.
Ju-Hong
JH
Jeon
Department of Physiology, Seoul National University College of Medicine, Seoul, Republic of Korea.
Insuk
I
So
Department of Biochemistry, Seoul National University College of Medicine, Seoul, Republic of Korea.
In-Gyu
IG
Kim
Institute of Endemic Disease, Seoul National University Medical Research Center and Bundang Hospital, Jongno-Gu, Seoul 110-799, Republic of Korea.|Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul, Republic of Korea.
Myung-Sik
MS
Choi
Institute of Endemic Disease, Seoul National University Medical Research Center and Bundang Hospital, Jongno-Gu, Seoul 110-799, Republic of Korea.|Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul, Republic of Korea.
Ik-Sang
IS
Kim
Division of Biochemistry, College of Medicine, Chungbuk National University, Cheongju 361-763, Republic of Korea.
Joong-Kook
JK
Choi
Molecular Microbiology and Immunology, University of Southern California, School of Medicine, 2011 Zonal Avenue, HMR401, Los Angeles, CA 90033, USA.
Jae Ung
JU
Jung
Institute of Endemic Disease, Seoul National University Medical Research Center and Bundang Hospital, Jongno-Gu, Seoul 110-799, Republic of Korea.|Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul, Republic of Korea.
Nam-Hyuk
NH
Cho
D021581:Active Transport, Cell Nucleus; D002472:Cell Transformation, Viral; D006567:Herpesvirus 2, Saimiriine / Q000472:pathogenicity*; D006801:Humans; D019169:Jurkat Cells / Q000276:immunology* / Q000821:virology*; D010750:Phosphoproteins / Q000378:metabolism*; D025941:Protein Interaction Mapping; D050800:STAT6 Transcription Factor / Q000378:metabolism*; D014158:Transcription, Genetic; D014764:Viral Proteins / Q000378:metabolism*
D010750:Phosphoproteins; D050800:STAT6 Transcription Factor; C494101:STAT6 protein, human; D014764:Viral Proteins; C092384:tyrosine kinase interacting protein, Saimiriine herpesvirus 2