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Global re-wiring of p53 transcription regulation by the hepatitis B virus X protein.

Publication ,  Journal Article
Chan, C; Thurnherr, T; Wang, J; Gallart-Palau, X; Sze, SK; Rozen, S; Lee, CG
Published in: Mol Oncol
October 2016

BACKGROUND: The tumour suppressor p53 is a central player in transcription regulation and cell fate determination. By interacting with p53 and altering its sequence-specific binding to the response elements, the hepatitis B virus X protein (HBx) was reported to re-direct p53 regulation of some genes. RESULTS: Coupling massively parallel deep sequencing with p53 chromatin immunoprecipitation, we demonstrate that HBx modulates global p53 site selection and that this was strongly influenced by altered interaction with transcription co-factors/co-regulators as well as post-translational modifications. Specifically, HBx attenuated p53-TBP-RB1 transcription complex recruitment and interaction and this was associated with hyper-phosphorylation of p53 at serine 315 by HBx. Concurrently, HBx enhanced p53 DNA occupancy to other response elements either alone by displacing specific transcription factors such as CEBPB and NFkB1, or in complex with distinct interacting co-factors Sp1, JUN and E2F1. Importantly, re-wiring of p53 transcription regulation by HBx was linked to the deregulation of genes involved in cell proliferation and death, suggesting a role of HBx in errant cell fate determination mediated by altered p53 site selection of target genes. CONCLUSIONS: Our study thus presents first evidence of global modes of p53 transcription alteration by HBx and provides new insights to understand and potentially curtail the viral oncoprotein.

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Published In

Mol Oncol

DOI

EISSN

1878-0261

Publication Date

October 2016

Volume

10

Issue

8

Start / End Page

1183 / 1195

Location

United States

Related Subject Headings

  • Viral Regulatory and Accessory Proteins
  • Tumor Suppressor Protein p53
  • Transcription, Genetic
  • Transcription Factors
  • Trans-Activators
  • Response Elements
  • Protein Binding
  • Phosphoserine
  • Phosphorylation
  • Oncology & Carcinogenesis
 

Citation

APA
Chicago
ICMJE
MLA
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Chan, C., Thurnherr, T., Wang, J., Gallart-Palau, X., Sze, S. K., Rozen, S., & Lee, C. G. (2016). Global re-wiring of p53 transcription regulation by the hepatitis B virus X protein. Mol Oncol, 10(8), 1183–1195. https://doi.org/10.1016/j.molonc.2016.05.006
Chan, Cheryl, Thomas Thurnherr, Jingbo Wang, Xavier Gallart-Palau, Siu Kwan Sze, Steve Rozen, and Caroline G. Lee. “Global re-wiring of p53 transcription regulation by the hepatitis B virus X protein.Mol Oncol 10, no. 8 (October 2016): 1183–95. https://doi.org/10.1016/j.molonc.2016.05.006.
Chan C, Thurnherr T, Wang J, Gallart-Palau X, Sze SK, Rozen S, et al. Global re-wiring of p53 transcription regulation by the hepatitis B virus X protein. Mol Oncol. 2016 Oct;10(8):1183–95.
Chan, Cheryl, et al. “Global re-wiring of p53 transcription regulation by the hepatitis B virus X protein.Mol Oncol, vol. 10, no. 8, Oct. 2016, pp. 1183–95. Pubmed, doi:10.1016/j.molonc.2016.05.006.
Chan C, Thurnherr T, Wang J, Gallart-Palau X, Sze SK, Rozen S, Lee CG. Global re-wiring of p53 transcription regulation by the hepatitis B virus X protein. Mol Oncol. 2016 Oct;10(8):1183–1195.

Published In

Mol Oncol

DOI

EISSN

1878-0261

Publication Date

October 2016

Volume

10

Issue

8

Start / End Page

1183 / 1195

Location

United States

Related Subject Headings

  • Viral Regulatory and Accessory Proteins
  • Tumor Suppressor Protein p53
  • Transcription, Genetic
  • Transcription Factors
  • Trans-Activators
  • Response Elements
  • Protein Binding
  • Phosphoserine
  • Phosphorylation
  • Oncology & Carcinogenesis