Stimulation of inducible nitric oxide by hepatitis B virus transactivator protein HBx requires MTA1 coregulator.

ABSTRACT: Nitric oxide has been implicated in the pathogenesis of inflammatory disorders, including hepatitis B virus-associated hepatocellular carcinoma. Transactivator protein HBx, a major regulator of cellular responses of hepatitis B virus, is known to induce the expression of MTA1 (metastasis-associated protein 1) coregulator via NF-kappaB signaling in hepatic cells. However, the underlying mechanism of HBx regulation of the inducible nitric-oxide synthase (iNOS) pathway remains unknown. Here we provide evidence that MTA1 is a positive regulator of iNOS transcription and plays a mechanistic role in HBx stimulation of iNOS expression and activity. We found that the HBx-MTA1 complex is recruited onto the human iNOS promoter in an NF-kappaB-dependent manner. Pharmacological inhibition of the NF-ka

SUBMITTER: Bui-Nguyen TM 

PROVIDER: S-EPMC2844147 | biostudies-literature | 2010 Mar

REPOSITORIES: biostudies-literature