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

Because HBx also activates CREB and is required for HBV replication (10, 19) , we investigated the interplay among HBx, CREB and CRTC1 in HBV transcription. We observed that CRTC1 activation of both canonical CREs and the preS2 promoter was more robust when HBx was also expressed ( Figure 6A and B, groups 5 and 6 compared to 4). Similar results were also obtained for CRTC2 and CRTC3 (data not shown). In addition, CRTC1 was detected in the HBx immunoprecipitate ( Figure 6C , lane 3 compared to 2), indicating their association in cultured cells. Interestingly, the protein bands of both CRTC1 and HBx were more prominent when they were co-expressed ( Figure 6C , lane 3 compared to 1 and 2), implicating a mutual stabilization effect. Unexpectedly, an additional slow-migrating HBx species was observed when CRTC1 was co-expressed ( Figure 6C , lane 3 compared to 1). Thus, CRTC1 might direct HBx for additional protein modifications.