title: Ubiquitin-dependent and -independent proteasomal degradation of hepatitis B virus X protein.
abstract: The hepatitis B virus X protein (HBX) plays key regulatory roles in viral replication and the development of hepatocellular carcinoma. HBX is an unstable protein; its instability is attributed to rapid degradation through the ubiquitin-proteasome pathway. Here, we show that the middle and carboxyl-terminal domains of HBX, independently fused to GFP, render the recombinant proteins susceptible to proteasomal degradation, while the amino-terminal domain has little effect on the ubiquitination or stability of HBX. Mutation of any single or combination of up to five of six lysine residues, all located in the middle and carboxyl-terminal domain, did not prevent HBX from being ubiquitinated, ruling out any specific lysine as the sole site of ubiquitination. Surprisingly, HBX in which all six lysines were mutated and showed no evidence of ubiquitination, was still susceptible to proteasomal degradation. These results suggest that both ubiquitin-dependent and -independent proteasomal degradation processes are operative in HBX turnover.
authors.affiliation: School of Life Sciences & Biotechnology, Korea University, Anamdong 5-1, Sungbuk, Seoul 136-701, Republic of Korea.
authors.forename: Jung-Hwan
authors.initials: JH
authors.lastname: Kim
authors.forename: Sook-Young
authors.initials: SY
authors.lastname: Sohn
authors.forename: T S
authors.initials: TS
authors.lastname: Benedict Yen
authors.forename: Byung-Yoon
authors.initials: BY
authors.lastname: Ahn
mesh_terms: D006801:Humans; D008239:Lysine; D050505:Mutant Proteins / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary; D013329:Structure-Activity Relationship; D015534:Trans-Activators / Q000737:chemistry / Q000378:metabolism*; D025801:Ubiquitin / Q000378:metabolism*; D054875:Ubiquitination; D054334:Viral Regulatory and Accessory Proteins
chemical_list: D050505:Mutant Proteins; D015534:Trans-Activators; D025801:Ubiquitin; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein; D046988:Proteasome Endopeptidase Complex; D008239:Lysine