E3 ubiquitin ligase Siah-1 facilitates poly-ubiquitylation and proteasomal degradation of the hepatitis B viral X protein

Hepatitis B viral X protein (HBx) is a multifunctional transactivator and implicated in hepatitis B virus (HBV) replication and hepatocarcinogenesis. HBx can be ubiquitinated and degraded through ubiquitin-proteasome pathway. However, the E3 ubiquitin ligase regulating HBx ubiquitin-dependent degradation is still unknown. In this study, we identified Siah-1 as a novel E3 ubiquitin ligase for HBx, which interacted with HBx and facilitated HBx poly-ubiquitylation and proteasomal degradation. Co-expression of Siah-1 attenuated the transcriptional transactivation of HBx on glucocorticoid response element (GRE), heat shock response element (HSE) and cAMP response element (CRE) signal pathways. Moreover, Siah-1 participated in p53-mediated HBx degradation. Therefore, Siah-1 may play important roles in ubiquitin-dependent degradation of HBx and may be involved in suppressing the progression of hepatocellular carcinoma (HCC). Structured summary of protein interactions: SIAH1 and HBx colocalize by fluorescence microscopy (View interaction) SIAH1 physically interacts with HBx by anti tag coimmunoprecipitation (View interaction) HBx physically interacts with SIAH1 by anti tag coimmunoprecipitation (View interaction) SIAH1 binds to HBx by pull down (View interaction).