title: Hepatitis B virus x protein induces autophagy via activating death-associated protein kinase.
abstract: Hepatitis B virus x protein (HBX), a product of hepatitis B virus (HBV), is a multifunctional protein that regulates viral replication and various cellular functions. Recently, HBX has been shown to induce autophagy; however, the responsible mechanism is not fully known. In this study, we established stable HBX-expressing epithelial Chang cells as the platform to study how HBX induced autophagy. The results showed that the overexpression of HBX resulted in starvation-induced autophagy. HBX-induced autophagy was related to its ability to dephosphorylate/activate death-associated protein kinase (DAPK). The block of DAPK by its siRNA significantly counteracted HBX-mediated autophagy, confirming the positive role of DAPK in this process. HBX also induced Beclin 1, which functions at the downstream of the DAPK-mediated autophagy pathway. Although HBX could activate JNK, a kinase known to participate in autophagy in certain conditions, the change in JNK failed to influence HBX-induced autophagy. In conclusion, HBX induces autophagy via activating DAPK in a pathway related to Beclin 1, but not JNK. This new finding should help us to understand the role of autophagy in HBX-mediated pathogenesis and thus may provide targets for intervening HBX-related disorders.
authors.affiliation: Department of Surgery, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China; Department of Biochemistry and Molecular Biology, Guangdong Medical College, Zhanjiang, China.
authors.forename: H-T
authors.initials: HT
authors.lastname: Zhang
authors.forename: G G
authors.initials: GG
authors.lastname: Chen
authors.forename: B-G
authors.initials: BG
authors.lastname: Hu
authors.forename: Z-Y
authors.initials: ZY
authors.lastname: Zhang
authors.forename: J-P
authors.initials: JP
authors.lastname: Yun
authors.forename: M-L
authors.initials: ML
authors.lastname: He
authors.forename: P B S
authors.initials: PB
authors.lastname: Lai
mesh_terms: D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001343:Autophagy; D000071186:Beclin-1; D002460:Cell Line; D064550:Death-Associated Protein Kinases / Q000378:metabolism*; D006515:Hepatitis B virus / Q000502:physiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism*; D054334:Viral Regulatory and Accessory Proteins
chemical_list: D051017:Apoptosis Regulatory Proteins; C491997:BECN1 protein, human; D000071186:Beclin-1; D008565:Membrane Proteins; D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein; D064550:Death-Associated Protein Kinases
keywords: Beclin1; autophagy; death-associated protein kinase; hepatitis B virus x protein