Kaposi's sarcoma-associated herpesvirus transactivator RTA promotes degradation of the repressors to regulate viral lytic replication

Kaposi's sarcoma-associated herpesvirus/human herpesvirus 8 (KSHV/HHV-8) RTA is an important protein involved in the induction of KSHV lytic replication from latency through activation of the lytic cascade. A number of cellular and viral proteins, including K-RBP, have been found to repress RTA-mediated transactivation and KSHV lytic replication. However, it is unclear as to how RTA overcomes the suppression during lytic reactivation. In this study, we found that RTA can induce K-RBP degradation through the ubiquitin-proteasome pathway and that two regions in RTA are responsible. Moreover, we found that RTA can promote the degradation of several other RTA repressors. RTA mutants that are defective in inducing K-RBP degradation cannot activate RTA responsive promoter as efficiently as wild-type RTA. Interference of the ubiquitin-proteasome pathway affected RTA-mediated transactivation and KSHV reactivation from latency. Our results suggest that KSHV RTA can stimulate the turnover of repressors to modulate viral reactivation. Since herpes simplex virus type 1 transactivator ICP0 and human cytomegalovirus transactivator pp71 also stimulate the degradation of cellular silencers, it is possible that the promotion of silencer degradation by viral transactivators may be a common mechanism for regulating the lytic replication of herpesviruses.     

KRAB型锌指蛋白(KZNF)的研究进展

KRAB型锌指蛋白是哺乳动物中最大的转录调控因子家族, 它的多数成员在基因组上成簇分布。其结构特征是N端含有KRAB结构域, C端含有多个C2H2型锌指结构。KRAB结构域为一蛋白质-蛋白质相互作用区, 可以与多种协同转录抑制因子和转录因子结合, 使KRAB型锌指蛋白作为转录因子和/或转录调控因子发挥依赖于DNA结合的转录抑制功能, 在胚胎发育、细胞分化、细胞转化及细胞周期的调控中发挥重要功能。