Human I-mfa domain proteins specifically interact with KSHV LANA and affect its regulation of Wnt signaling-dependent transcription.
Kaposi's sarcoma-associated herpes virus (KSHV)-encoded latency-associated nuclear antigen (LANA) protein has been reported to interact with glycogen synthase kinase 3beta (GSK-3beta) and to negatively regulate its activity, leading to stimulation of GSK-3beta-dependent beta-catenin degradation. We show here that the I-mfa domain proteins, HIC (human I-mfa domain-containing protein) and I-mfa (inhibitor of MyoD family a), interacted in vivo with LANA through their C-terminal I-mfa domains. This interaction affected the intracellular localization of HIC, inhibited the LANA-dependent transactivation of a beta-catenin-regulated reporter construct, and decreased the level of the LANA.GSK-3beta complex. These data reveal for the first time that I-mfa domain proteins interact with LANA and negatively regulate LANA-mediated activation of Wnt signaling-dependent transcription by inhibiting the formation of the LANA.GSK-3beta complex.
Kusano
Shuichi
S
Division of Persistent and Oncogenic Viruses, Center for Chronic Viral Diseases, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan. skusano@m2.kufm.kagoshima-u.ac.jp
Eizuru
Yoshito
Y
D000818:Animals; D000956:Antigens, Viral / Q000378:metabolism*; D019556:COS Cells; D002460:Cell Line; D002522:Chlorocebus aethiops; D015967:Gene Expression Regulation, Viral; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism; D019288:Herpesvirus 8, Human / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D018006:Myogenic Regulatory Factors / Q000378:metabolism*; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction; D014158:Transcription, Genetic; D051153:Wnt Proteins / Q000378:metabolism*
D000956:Antigens, Viral; C478034:MDFIC protein, human; D018006:Myogenic Regulatory Factors; D009687:Nuclear Proteins; D051153:Wnt Proteins; C109540:latency-associated nuclear antigen; C101295:MDFI protein, human; D038362:Glycogen Synthase Kinase 3