title: Identifying and Characterizing Interplay between Hepatitis B Virus X Protein and Smc5/6.
abstract: Hepatitis B X protein (HBx) plays an essential role in the hepatitis B virus (HBV) replication cycle, but the function of HBx has been elusive until recently. It was recently shown that transcription from the HBV genome (covalently-closed circular DNA, cccDNA) is inhibited by the structural maintenance of chromosome 5/6 complex (Smc5/6), and that a key function of HBx is to redirect the DNA-damage binding protein 1 (DDB1) E3 ubiquitin ligase to target this complex for degradation. By doing so, HBx alleviates transcriptional repression by Smc5/6 and stimulates HBV gene expression. In this review, we discuss in detail how the interplay between HBx and Smc5/6 was identified and characterized. We also discuss what is known regarding the repression of cccDNA transcription by Smc5/6, the timing of HBx expression, and the potential role of HBx in promoting hepatocellular carcinoma (HCC).
authors.affiliation: Gilead Sciences, Foster City, CA 94404, USA. christine.marie.livingston@gmail.com.
authors.forename: Christine M
authors.initials: CM
authors.lastname: Livingston
authors.affiliation: Gilead Sciences, Foster City, CA 94404, USA. Dhivya.Ramakrishnan@gilead.com.
authors.forename: Dhivya
authors.initials: D
authors.lastname: Ramakrishnan
authors.affiliation: Department of Microbiology and Molecular Medicine, University Medical Center (CMU), 1211 Geneva, Switzerland. Michel.Strubin@unige.ch.
authors.forename: Michel
authors.initials: M
authors.lastname: Strubin
authors.affiliation: Gilead Sciences, Foster City, CA 94404, USA. simon.fletcher@gilead.com.
authors.forename: Simon P
authors.initials: SP
authors.lastname: Fletcher
authors.affiliation: Gilead Sciences, Foster City, CA 94404, USA. rudolf.beran@gilead.com.
authors.forename: Rudolf K
authors.initials: RK
authors.lastname: Beran
mesh_terms: D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors*; D002868:Chromosomal Proteins, Non-Histone; D006515:Hepatitis B virus / Q000276:immunology* / Q000502:physiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D015534:Trans-Activators / Q000378:metabolism*; D054334:Viral Regulatory and Accessory Proteins; D014779:Virus Replication
chemical_list: D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; C432931:SMC5 protein, human; C432932:SMC6 protein, human; D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein
keywords: DDB1; HBV; HBx; Smc5/6; cccDNA