Interaction of hepatitis B virus X protein with damaged DNA-binding protein p127: Structural analysis and identification of antagonists

2002 ◽  
Vol 9 (6) ◽  
pp. 706-715 ◽  
Author(s):  
Françoise Bergametti ◽  
Julie Bianchi ◽  
Catherine Transy
Keyword(s):  
Hepatitis B Virus ◽  
Structural Analysis ◽  
Dna Binding ◽  
Hepatitis B ◽  
Binding Protein ◽  
Dna Binding Protein ◽  
X Protein ◽  
B Virus ◽  
Damaged Dna

scholarly journals Hepatitis B Virus X Protein Interferes with Cell Viability through Interaction with the p127-kDa UV-Damaged DNA-Binding Protein

Virology ◽  
2001 ◽  
Vol 287 (2) ◽  
pp. 266-274 ◽  
Author(s):  
Nathalie Lin-Marq ◽  
Séverine Bontron ◽  
Olivier Leupin ◽  
Michel Strubin
Keyword(s):  
Hepatitis B Virus ◽  
Dna Binding ◽  
Hepatitis B ◽  
Cell Viability ◽  
Binding Protein ◽  
Dna Binding Protein ◽  
X Protein ◽  
B Virus ◽  
Damaged Dna

Hepatitis B virus X protein affects S phase progression leading to chromosome segregation defects by binding to damaged DNA binding protein 1

Hepatology ◽  
2008 ◽  
Vol 48 (5) ◽  
pp. 1467-1476 ◽  
Author(s):  
Silvia Martin-Lluesma ◽  
Céline Schaeffer ◽  
Eva Isabelle Robert ◽  
Pieter Cornelis van Breugel ◽  
Olivier Leupin ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Dna Binding ◽  
Hepatitis B ◽  
Chromosome Segregation ◽  
Binding Protein ◽  
Dna Binding Protein ◽  
S Phase ◽  
X Protein ◽  
B Virus ◽  
Phase Progression

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.

scholarly journals Correction: The hepatitis B virus X protein functionally interacts with CREB-binding protein/p300 in the regulation of CREB-mediated transcription.

2020 ◽  
Vol 295 (9) ◽  
pp. 2888-2888
Author(s):  
Delphine Cougot ◽  
Yuanfei Wu ◽  
Stefano Cairo ◽  
Julie Caramel ◽  
Claire-Angélique Renard ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Binding Protein ◽  
Creb Binding Protein ◽  
X Protein ◽  
B Virus

scholarly journals The Hepatitis B Virus X Protein Functionally Interacts with CREB-binding Protein/p300 in the Regulation of CREB-mediated Transcription

2006 ◽  
Vol 282 (7) ◽  
pp. 4277-4287 ◽  
Author(s):  
Delphine Cougot ◽  
Yuanfei Wu ◽  
Stefano Cairo ◽  
Julie Caramel ◽  
Claire-Angélique Renard ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Proliferating Cell Nuclear Antigen ◽  
Binding Protein ◽  
Interleukin 8 ◽  
Nuclear Antigen ◽  
Creb Binding Protein ◽  
X Protein ◽  
B Virus ◽  
Proliferating Cell

The hepatitis B virus infects more than 350 million people worldwide and is a leading cause of liver cancer. The virus encodes a multifunctional regulator, the hepatitis B virus X protein (HBx), that is essential for virus replication. HBx is involved in modulating signal transduction pathways and transcription mediated by various factors, notably CREB that requires the recruitment of the co-activators CREB-binding protein (CBP)/p300. Here we investigated the role of HBx and its potential interaction with CBP/p300 in regulating CREB transcriptional activity. We show that HBx and CBP/p300 synergistically enhanced CREB activity and that CREB phosphorylation by protein kinase A was a prerequisite for the cooperative action of HBx and CBP/p300. We further show that HBx interacted directly with CBP/p300 in vitro and in vivo. Using chromatin immunoprecipitation, we provide evidence that HBx physically occupied the CREB-binding domain of CREB-responsive promoters of endogenous cellular genes such as interleukin 8 and proliferating cell nuclear antigen. Moreover expression of HBx increased the recruitment of p300 to the interleukin 8 and proliferating cell nuclear antigen promoters in cells, and this is associated with increased gene expression. As recruitment of CBP/p300 is known to represent the limiting event for activating CREB target genes, HBx may disrupt this cellular regulation, thus predisposing cells to transformation.

scholarly journals Hepatitis B Virus X Protein Interferes with Cellular DNA Repair

1998 ◽  
Vol 72 (1) ◽  
pp. 266-272 ◽  
Author(s):  
Sherry A. Becker ◽  
Teh-Hsiu Lee ◽  
Janet S. Butel ◽  
Betty L. Slagle
Keyword(s):  
Dna Repair ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Excision Repair ◽  
Normal Function ◽  
X Protein ◽  
B Virus ◽  
Cellular Dna ◽  
Host Cell Reactivation ◽  
Damaged Dna

ABSTRACT The hepatitis B virus X protein (HBx) is a broadly acting transactivator implicated in the development of liver cancer. Recently, HBx has been reported to interact with several different cellular proteins, including our report of its binding to XAP-1, the human homolog of the simian repair protein UVDDB. In the present study, several HBx mutants were used to localize the minimal domain of HBx required for binding to XAP-1/UVDDB to amino acids 55 to 101. The normal function of XAP-1/UVDDB is thought to involve binding to damaged DNA, the first step in nucleotide excision repair (NER); therefore, we hypothesized that this interaction may affect the cell’s capacity to correct lesions in the genome. When tested in two independent assays that measure NER (unscheduled DNA synthesis and host cell reactivation), the expression of HBx significantly inhibited the ability of cells to repair damaged DNA. Under the assay conditions, HBx was expressed at a level similar to that previously observed during natural viral infection and was able to transactivate several target reporter genes. These results are consistent with a model in which HBx acts as a cofactor in hepatocarcinogenesis by preventing the cell from efficiently repairing damaged DNA, thus leading to an accumulation of DNA mutations and, eventually, cancer. An adverse effect on cellular DNA repair processes suggests a new mechanism by which a tumor-associated virus might contribute to carcinogenesis.

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