Abstract

Hepatitis B Virus and DNA Repair We and others have previously reported that p53 can modulate nucleotide excision repair. Using a host reactivation assay, our preliminary data indicate that HBx inhibits reactivation, i.e., repair of the ultraviolet light (UV-C, 254 nm) damage plasmid. This leads to the hypothesis that HBx inhibits p53 binding to XPB or XPD DNA helicases in the basal transcription-nucleotide excision repair complex, TFIIH. We have previously demonstrated that HBx protein inhibits in vitro p53 binding to XPB. HBx binds to XPB. HBx binds to the carboxyl terminus of p53 which also is the site of XPB binding. We are currently investigating the hypothesis that HBx binds to other members of the TFIIH multiprotein complex. We are attempting to obtain crystals of HBVX and co-crystals of its binding partners for fine detail structural analysis.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Intramural Research (Z01)
Project #
1Z01BC005793-03
Application #
6160978
Study Section
Special Emphasis Panel (LHC)
Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
1997
Total Cost
Indirect Cost

  Institution

Name
National Cancer Institute Division of Basic Sciences
Department
Type
DUNS #
City
State
Country
United States
Zip Code

  Publications

Zhao, Xuelian; Ji, Junfang; Yu, Li-Rong et al. (2015) Cell cycle-dependent phosphorylation of nucleophosmin and its potential regulation by peptidyl-prolyl cis/trans isomerase. J Mol Biochem 4:95-103
Ji, Junfang; Wang, Xin Wei (2010) A Yin-Yang balancing act of the lin28/let-7 link in tumorigenesis. J Hepatol :
Budhu, A; Chen, Y; Kim, J W et al. (2007) Induction of a unique gene expression profile in primary human hepatocytes by hepatitis C virus core, NS3 and NS5A proteins. Carcinogenesis 28:1552-60
Lim, Mi Jung; Wang, Xin Wei (2006) Nucleophosmin and human cancer. Cancer Detect Prev 30:481-90
Zhang, Yuexing; Wang, Xin-Wei; Jelovac, Danijela et al. (2005) The ErbB3-binding protein Ebp1 suppresses androgen receptor-mediated gene transcription and tumorigenesis of prostate cancer cells. Proc Natl Acad Sci U S A 102:9890-5
Wang, Wei; Budhu, Anuradha; Forgues, Marshonna et al. (2005) Temporal and spatial control of nucleophosmin by the Ran-Crm1 complex in centrosome duplication. Nat Cell Biol 7:823-30
Budhu, Anuradha S; Wang, Xin W (2005) Loading and unloading: orchestrating centrosome duplication and spindle assembly by Ran/Crm1. Cell Cycle 4:1510-4
Forgues, Marshonna; Difilippantonio, Michael J; Linke, Steven P et al. (2003) Involvement of Crm1 in hepatitis B virus X protein-induced aberrant centriole replication and abnormal mitotic spindles. Mol Cell Biol 23:5282-92
Staib, Frank; Hussain, S Perwez; Hofseth, Lorne J et al. (2003) TP53 and liver carcinogenesis. Hum Mutat 21:201-16
Linke, Steven P; Sengupta, Sagar; Khabie, Nissim et al. (2003) p53 interacts with hRAD51 and hRAD54, and directly modulates homologous recombination. Cancer Res 63:2596-605