Enhancement of gene transactivation activity of androgen receptor by hepatitis B virus X protein |
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Authors: | Zheng Yanyan Chen Wen-Ling Ma W-L Maverick Chang Chawnshang Ou J-H James |
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Institution: | Department of Molecular Microbiology and Immunology, University of Southern California, Keck School of Medicine, 2011 Zonal Avenue, HMR-401, Los Angeles, CA 90033, USA. |
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Abstract: | Hepatitis B virus (HBV) X protein (HBx) is a regulatory protein that is required for efficient replication of HBV in its natural host. In this report, we demonstrate by co-immunoprecipitation experiments that HBx can physically bind to the androgen receptor (AR), which is a nuclear hormone receptor that is expressed in many different tissues including the liver. This observation is further supported by confocal microscopy, which reveals that HBx can alter the subcellular localization of the AR both in the presence and in the absence of dihydrotestosterone (DHT). Further studies indicate that HBx can enhance the gene transactivation activity of AR by enhancing its DNA binding activity in a DHT-dependent manner. However, HBx does not remain associated with AR on the DNA. As AR can regulate the expression of a number of cellular genes, our results raise the possibility that HBV pathogenesis may be mediated in part via the interaction between HBx and AR. |
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Keywords: | Hepatitis B virus HBV X protein Androgen receptor Dihydrotestosterone Gene transactivation Hepatocellular carcinoma Chromatin immunoprecipitation |
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