Physical and functional interactions between STAT3 and Kaposi's sarcoma-associated herpesvirus-encoded LANA.
The Kaposi's sarcoma-associated herpesvirus (KSHV)-encoded latency-associated nuclear antigen (LANA) is known to modulate viral and cellular gene expression. We show that LANA directly associates with an interleukin-6 signal transducer, signal transducer and activator of transcription 3 (STAT3) and that LANA enhances the transcriptional activity of STAT3. Coimmunoprecipitation studies documented a physical interaction between LANA and STAT3 in transiently transfected 293T cells as well as the KSHV-infected primary effusion lymphoma (PEL) cell line. Furthermore, small-interfering RNA-mediated reduction of LANA expression decreased the STAT3-dependent transcription in KSHV-positive PEL cells, whereas overexpression of LANA enhanced STAT3 activity in KSHV-negative B lymphoma cells. These data demonstrate that LANA is a transcriptional co-activator of STAT3, and may have implications for the pathogenesis of KSHV-associated diseases.
Muromoto
Ryuta
R
Department of Immunology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan.
Okabe
Kanako
K
Fujimuro
Masahiro
M
Sugiyama
Kenji
K
Yokosawa
Hideyoshi
H
Seya
Tsukasa
T
Matsuda
Tadashi
T
D000956:Antigens, Viral / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D019288:Herpesvirus 8, Human / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity; D006801:Humans; D016393:Lymphoma, B-Cell / Q000235:genetics / Q000378:metabolism / Q000821:virology; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D034741:RNA, Small Interfering / Q000235:genetics / Q000494:pharmacology; D050796:STAT3 Transcription Factor / Q000096:biosynthesis* / Q000235:genetics; D012514:Sarcoma, Kaposi / Q000235:genetics / Q000378:metabolism / Q000821:virology; D014158:Transcription, Genetic
D000956:Antigens, Viral; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C109540:latency-associated nuclear antigen