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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

Regulation of MCP-1 chemokine transcription by p53

Katrin Hacke1, Bladimiro Rincon-Orozco, Gilles Buchwalter

  • 1Deutsches Krebsforschungszentrum, Forschungsschwerpunkt Infektion und Krebs, Abteilung Virale Transformationsmechanismen, Heidelberg, Germany.

Molecular Cancer
|April 22, 2010
PubMed
Abstract

Insights

The tumor suppressor p53 regulates monocyte chemoattractant protein-1 (MCP-1) expression, a key chemokine. Inactivation of p53 impairs immune surveillance by reducing MCP-1, impacting communication with immune cells.

Area of Science:

  • Oncology
  • Immunology
  • Molecular Biology

Background:

  • Monocyte chemoattractant protein-1 (MCP-1) expression is reduced in human papillomavirus (HPV)-positive cancers.
  • A potential p53 binding site was identified upstream of the MCP-1 gene.

Purpose of the Study:

  • To investigate the physiological role of p53 in regulating MCP-1 expression.

Main Methods:

  • Electrophoretic-mobility-shift assays (EMSA) and chromatin immunoprecipitation (ChIP) were used to confirm p53 binding.
  • Experiments involved HPV-positive and negative keratinocytes, cells with mutated p53, and siRNA-mediated p53 knockdown.

Main Results:

  • p53 binding to the MCP-1 promoter was confirmed in vitro and in vivo.
  • TNF-alpha-induced MCP-1 expression requires functional p53; p53 degradation in HPV-positive cells abrogates this induction.
  • Non-functional p53 in various cellular models led to diminished MCP-1 transcription.

Conclusions:

  • p53 plays a crucial role in regulating MCP-1 chemokine expression.
  • p53 inactivation during carcinogenesis impairs immune surveillance by affecting chemokine-mediated communication with immune cells.

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