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. 2011 Oct 3;585(19):2943-50.
doi: 10.1016/j.febslet.2011.08.015. Epub 2011 Aug 26.

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

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

Jing Zhao et al. FEBS Lett. .
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Abstract

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).

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