Requirement of CRTC1 coactivator for hepatitis B virus transcription

Tang, Hei-Man Vincent; Gao, Wei-Wei; Chan, Chi-Ping; Cheng, Yun; Chaudhary, Vidyanath; Deng, Jian-Jun; Yuen, Kit-San; Wong, Chun-Ming; Ng, Irene Oi-Lin; Kok, Kin-Hang; Zhou, Jie; Jin, Dong-Yan

The activation of the preS2 promoter by CRTC1 was mediated through CREB and CRE (Figures 2 and 5) . The structural interface of CRTC2 for recognition and coactivation of CREB has been determined (38) . In addition, the regulation of CRTC2 nucleocytoplasmic shuttling by upstream kinases has also been characterized (39) . Plausibly, CRTC1 would use a similar interface to recognize CREB and CRTC1 activity would be regulated by the same protein kinases in the context of HBV transcription. It is noteworthy that small molecule activators and inhibitors of LKB1 and its downstream protein kinases, including metformin and salicylate, have been well documented (16, 40) . We have recently shown that LKB1 and its downstream kinases potently suppress transcriptional activity of CRTC1 and CREB in the context of human T-cell leukemia type 1 virus infection. In addition, the activation of these kinases using small molecule agonists such as metformin exhibits strong antiretroviral effects (27) . By the same token, our characterization of the role of CRTCs in HBV life cycle will pave the way for further investigations on pharmacological inhibition of HBV transcription.