scholarly journals The hepatitis B virus X protein (HBx) induces a migratory phenotype in a CD44-dependent manner: Possible role of HBx in invasion and metastasis

Hepatology ◽  
2001 ◽  
Vol 33 (5) ◽  
pp. 1270-1281 ◽  
Author(s):  
E Lara-Pezzi
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Dependent Manner ◽  
Invasion And Metastasis ◽  
X Protein ◽  
B Virus ◽  
Migratory Phenotype

scholarly journals RMP, a Novel RNA Polymerase II Subunit 5-Interacting Protein, Counteracts Transactivation by Hepatitis B Virus X Protein

1998 ◽  
Vol 18 (12) ◽  
pp. 7546-7555 ◽  
Author(s):  
Dorjbal Dorjsuren ◽  
Yong Lin ◽  
Wenxiang Wei ◽  
Tatsuya Yamashita ◽  
Takahiro Nomura ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Rna Polymerase ◽  
Rna Polymerase Ii ◽  
Binding Protein ◽  
Host Protein ◽  
Dependent Manner ◽  
Binding Region ◽  
X Protein ◽  
B Virus

ABSTRACT To modulate transcription, regulatory factors communicate with basal transcription factors and/or RNA polymerases in a variety of ways. Previously, it has been reported that RNA polymerase II subunit 5 (RPB5) is one of the targets of hepatitis B virus X protein (HBx) and that both HBx and RPB5 specifically interact with general transcription factor IIB (TFIIB), implying that RPB5 is one of the communicating subunits of RNA polymerase II involved in transcriptional regulation. In this context, we screened for a host protein(s) that interacts with RPB5. By far-Western blot screening, we cloned a novel gene encoding a 508-amino-acid-residue RPB5-binding protein from a HepG2 cDNA library and designated it RPB5-mediating protein (RMP). Expression of RMP mRNA was detected ubiquitously in various tissues. Bacterially expressed recombinant RMP strongly bound RPB5 but neither HBx nor TATA-binding protein in vitro. Endogenous RMP was immunologically detected interacting with assembled RPB5 in RNA polymerase in mammalian cells. The central part of RMP is responsible for RPB5 binding, and the RMP-binding region covers both the TFIIB- and HBx-binding sites of RPB5. Overexpression of RMP, but not mutant RMP lacking the RPB5-binding region, inhibited HBx transactivation of reporters with different HBx-responsive cis elements in transiently transfected cells. The repression by RMP was counteracted by HBx in a dose-dependent manner. Furthermore, RMP has an inhibitory effect on transcriptional activation by VP16 in the absence of HBx. These results suggest that RMP negatively modulates RNA polymerase II function by binding to RPB5 and that HBx counteracts the negative role of RMP on transcription indirectly by interacting with RPB5.

The study on the role of Hepatitis B virus X protein and apoptosis in HBV intrauterine infection

2011 ◽  
Vol 285 (4) ◽  
pp. 943-949 ◽  
Author(s):  
Guiqin Bai ◽  
Yueling Wang ◽  
Lingyan Zhang ◽  
Yao Tang ◽  
Fengping Fu
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Intrauterine Infection ◽  
X Protein ◽  
B Virus

scholarly journals Hepatitis B Virus X Protein Induces Perinuclear Mitochondrial Clustering in Microtubule- and Dynein-Dependent Manners

2006 ◽  
Vol 81 (4) ◽  
pp. 1714-1726 ◽  
Author(s):  
Sujeong Kim ◽  
Hye-Young Kim ◽  
Seungmin Lee ◽  
Sung Woo Kim ◽  
Seonghyang Sohn ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Nuclear Periphery ◽  
Mitogen Activated Protein Kinase ◽  
Transport Systems ◽  
Dependent Manner ◽  
Atpase Inhibitor ◽  
X Protein ◽  
Hbv Replication ◽  
B Virus

ABSTRACT The hepatitis B virus (HBV) X protein (HBx) is thought to play a key role in HBV replication and the development of liver cancer. It became apparent that HBx induces mitochondrial clustering at the nuclear periphery, but the molecular basis for mitochondrial clustering is not understood. Since mitochondria move along the cytoskeleton as a cargo of motor proteins, we hypothesized that mitochondrial clustering induced by HBx occurs by an altered intracellular motility. Here, we demonstrated that the treatment of HBx-expressing cells with a microtubule-disrupting drug (nocodazole) abrogated mitochondrial clustering, while the removal of nocodazole restored clustering within 30 to 60 min, indicating that mitochondrial transport is occurring in a microtubule-dependent manner. The addition of a cytochalasin D-disrupting actin filament, however, did not measurably affect mitochondrial clustering. Mitochondrial clustering was further studied by observations of HBV-related hepatoma cells and HBV-replicating cells. Importantly, the abrogation of the dynein activity in HBx-expressing cells by microinjection of a neutralizing anti-dynein intermediate-chain antibody, dynamitin overexpression, or the addition of a dynein ATPase inhibitor significantly suppressed the mitochondrial clustering. In addition, HBx induced the activation of the p38 mitogen-activated protein kinase (MAPK) and inhibition of the p38 kinase activity by SB203580-attenuated HBx-induced mitochondrial clustering. Taken together, HBx activation of the p38 MAPK contributed to the increase in the microtubule-dependent dynein activity. The data suggest that HBx plays a novel regulatory role in subcellular transport systems, perhaps facilitating the process of maturation and/or assembly of progeny particles during HBV replication. Furthermore, mitochondrion aggregation induced by HBx may represent a cellular process that underlies disease progression during chronic viral infection.

scholarly journals NEDD4 Induces K48-Linked Degradative Ubiquitination of Hepatitis B Virus X Protein and Inhibits HBV-Associated HCC Progression

2021 ◽  
Vol 11 ◽  
Author(s):  
Tao Wan ◽  
Zhao Lei ◽  
Biao Tu ◽  
Tianyin Wang ◽  
Jiale Wang ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Progression Free Survival ◽  
Suppressive Effect ◽  
Hbv Infection ◽  
Migration And Invasion ◽  
Dependent Manner ◽  
X Protein ◽  
B Virus ◽  
Gene 4

Neural precursor cell expressed developmentally downregulated gene 4 (NEDD4) plays two opposite roles in carcinogenesis. It has been reported that NEDD4 inhibits hepatocellular carcinoma (HCC) progression; however, little is known about its potential function and molecular mechanism in HCC in the context of hepatitis B virus (HBV) infection. In this study, we analyzed NEDD4 expression in 199 HCC specimens with or without HBV infection and observed that NEDD4 expression was unrelated to HBV exposure in HCC tumor tissue but that high NEDD4 expression conferred better overall survival (OS) and progression-free survival (PFS) than low NEDD4 expression in patients with HBV-associated HCC. Upregulation of NEDD4 inhibited proliferation, migration and invasion in HBV-related HCC cell lines. We demonstrated that NEDD4 interacts with HBV X protein (HBx) and that HBx upregulation could reverse the suppression of proliferation and mobility induced by NEDD4 overexpression. Furthermore, we confirmed that NEDD4 induced the degradation of HBx in a ubiquitin/proteasome-dependent manner via K48-linked ubiquitination. Our findings suggest that NEDD4 exerts a tumor-suppressive effect in HBV-associated HCC by acting as an E3 ubiquitin ligase for HBx degradation and provide new insights into the function of NEDD4.

945 Central role of the hepatitis B virus X protein for the initiation of infection in primary hepatocytes

Hepatology ◽  
2003 ◽  
Vol 38 ◽  
pp. 612-612
Author(s):  
J KOCK ◽  
T BAUMERT ◽  
U PROTZER ◽  
H BLUM ◽  
F VONWEIZSACKER
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Primary Hepatocytes ◽  
X Protein ◽  
B Virus

scholarly journals Enhancement of Hepatitis B Virus Replication by Its X Protein in Transgenic Mice

2002 ◽  
Vol 76 (5) ◽  
pp. 2579-2584 ◽  
Author(s):  
Zhenming Xu ◽  
T. S. Benedict Yen ◽  
Lanying Wu ◽  
Charles R. Madden ◽  
Wenjie Tan ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Transgenic Mice ◽  
Viral Gene Expression ◽  
Viral Gene ◽  
X Protein ◽  
Multifunctional Protein ◽  
Hbv Replication ◽  
B Virus

ABSTRACT Hepatitis B virus (HBV) X gene encodes a multifunctional protein that can regulate cellular signaling pathways, interact with cellular transcription factors, and induce hepatocellular oncogenesis. In spite of its diverse activities, the precise role of the X protein in the viral life cycle of HBV remains unclear. To investigate this question, we have produced transgenic mice that carry either the wild-type HBV genome or a mutated HBV genome incapable of expressing the 16.5-kDa X protein. Our results indicate that while the X protein is not absolutely essential for HBV replication or its maturation in transgenic mice, it can enhance viral replication, apparently by activating viral gene expression. These results demonstrate a transactivation role of the X protein in HBV replication in transgenic mice.

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