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Yeast As a Chassis for Developing Functional Assays to Study Human P53
14:57

Yeast As a Chassis for Developing Functional Assays to Study Human P53

Published on: August 4, 2019

Transcriptional regulation of HIV-1 gene expression by p53

Ruma Mukerjee1, Pier Paolo Claudio, J Robert Chang

  • 1Molecular Virology Lab, Department of Neurology, Temple University School of Medicine, Philadelphia, PA, USA.

Cell Cycle (Georgetown, Tex.)
|November 20, 2010
PubMed

Insights

The tumor suppressor p53 inhibits human immunodeficiency virus type 1 (HIV-1) replication by blocking RNA polymerase II phosphorylation. This p53-mediated inhibition of HIV-1 transcription and replication suggests p53 as a potential therapeutic target for AIDS treatment.

Area of Science:

  • Molecular Biology
  • Virology
  • Immunology

Background:

  • The human immunodeficiency virus type 1 long terminal repeat (HIV-1 LTR) is crucial for viral replication.
  • Previous studies suggest p53 negatively regulates HIV-1 LTR transcription, but the mechanism is unclear.

Purpose of the Study:

  • To elucidate the mechanism by which p53 inhibits HIV-1 transcription and replication.
  • To investigate p53's role in regulating RNA polymerase II activity during HIV-1 infection.

Main Methods:

  • Overexpression of wild-type p53 in primary microglia and astrocytes.
  • Analysis of RNA polymerase II carboxyl-terminal domain (CTD) phosphorylation.
  • Assessment of HIV-1 transcriptional elongation and replication.

Main Results:

  • Overexpression of p53 prevented serine 2 phosphorylation in the RNA polymerase II CTD.
  • p53 significantly stalled transcriptional elongation on the HIV-1 LTR, reducing viral replication.
  • HIV-1 transcription and replication were eventually salvaged, suggesting a mitigating factor.

Conclusions:

  • p53 inhibits HIV-1 replication by impeding RNA polymerase II-dependent transcriptional elongation.
  • The negative effect of p53 on HIV-1 appears to be alleviated by another factor, potentially Pirh2.
  • p53 represents a potential therapeutic target for inhibiting HIV-1 gene expression and treating AIDS.

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