Kaposi's Sarcoma-associated herpesvirus open reading frame 50 stimulates the transcriptional activity of STAT3.
Kaposi's sarcoma-associated herpesvirus (KSHV) is an important pathogen in Kaposi's sarcoma and abnormal lymphoproliferation. KSHV open reading frame 50 (ORF50), a homolog of the Epstein-Barr virus immediate-early gene product RTA, activates early and late gene transcription in the KSHV lytic cycle, and its expression is closely correlated with KSHV-related diseases. ORF50 interacts with the cellular proteins CBP and histone deacetylase and represses p53-induced apoptosis through a CBP-related mechanism. We show here that KSHV ORF50 also interacts with STAT3. ORF50 stimulated transcription of STAT-driven reporter genes, and interleukin-6 and v-Src further activated this stimulating effect of ORF50. Physical association of STAT3 and ORF50 required the carboxyl-terminal transactivation domain of ORF50 and multiple regions within STAT3. ORF50 recruited STAT3 to the nucleus and induced the dimerization of STAT3 monomers in the absence of STAT3 phosphorylation. We show here that KSHV ORF50 activates STAT3-mediated transcription through direct interaction without mediating tyrosine phosphorylation.
Gwack
Yousang
Y
Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 305-701, Korea.
Hwang
Seungmin
S
Lim
Chunghun
C
Won
Young Suk
YS
Lee
Chul Ho
CH
Choe
Joonho
J
D016475:3T3 Cells; D021581:Active Transport, Cell Nucleus; D000818:Animals; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015967:Gene Expression Regulation, Viral; D019288:Herpesvirus 8, Human / Q000235:genetics*; D006801:Humans; D051379:Mice; D016366:Open Reading Frames; D010957:Plasmids; D011401:Promoter Regions, Genetic; D011994:Recombinant Proteins / Q000378:metabolism; D050796:STAT3 Transcription Factor; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D014162:Transfection
D004268:DNA-Binding Proteins; D011994:Recombinant Proteins; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C494087:Stat3 protein, mouse; D015534:Trans-Activators