title: E3 ubiquitin ligase Siah-1 facilitates poly-ubiquitylation and proteasomal degradation of the hepatitis B viral X protein.
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).
authors: State Key Laboratory of Genetic Engineering, Institute of Genetics, Shanghai, PR China.
authors: Jing
authors: J
authors: Zhao
authors: Chenji
authors: C
authors: Wang
authors: Jia
authors: J
authors: Wang
authors: Xianmei
authors: X
authors: Yang
authors: Ni
authors: N
authors: Diao
authors: Qiang
authors: Q
authors: Li
authors: Wenzhang
authors: W
authors: Wang
authors: Lingling
authors: L
authors: Xian
authors: Zhou
authors: Z
authors: Fang
authors: Long
authors: L
authors: Yu
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000209:etiology / Q000821:virology; D002460:Cell Line; D006509:Hepatitis B / Q000150:complications / Q000821:virology; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D025821:Polyubiquitin / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*; D054875:Ubiquitination; D054334:Viral Regulatory and Accessory Proteins; D000098563:Seven in Absentia Proteins
chemical_list: D009687:Nuclear Proteins; D015534:Trans-Activators; D016159:Tumor Suppressor Protein p53; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein; D025821:Polyubiquitin; D044767:Ubiquitin-Protein Ligases; D000098563:Seven in Absentia Proteins; D046988:Proteasome Endopeptidase Complex