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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

p53-mediated downregulation of H ferritin promoter transcriptional efficiency via NF-Y

Maria Concetta Faniello1, Maddalena Di Sanzo, Barbara Quaresima

  • 1Dipartimento di Medicina Sperimentale e Clinica "G. Salvatore", Università di Catanzaro "Magna Graecia", Campus Universitario, Germaneto, 88100 Catanzaro, Italy.

The International Journal of Biochemistry & Cell Biology
|March 29, 2008
PubMed

Insights

The tumor suppressor protein p53 downregulates H ferritin expression by interacting with NF-Y. This regulation requires p53

Area of Science:

  • Molecular Biology
  • Gene Regulation
  • Cancer Research

Background:

  • The tumor suppressor protein p53 is crucial for cellular responses to DNA damage.
  • p53 regulates target gene transcription through interactions with transcription factors like NF-Y.
  • H ferritin expression is regulated by the multiprotein complex Bbf, where NF-Y is essential.

Purpose of the Study:

  • To investigate the modulation of H ferritin expression levels by the p53 protein.
  • To elucidate the mechanism by which p53 influences H ferritin transcription.

Main Methods:

  • CAT reporter assays to assess transcriptional efficiency.
  • p53 siRNA to revert p53 overexpression effects.
  • Chromatin immunoprecipitation (ChIP) assays to detect protein-DNA interactions.
  • Electrophoretic mobility shift assays (EMSA) to analyze DNA-binding activity.

Main Results:

  • p53 overexpression significantly downregulates H ferritin transcription via the NF-Y recognition sequence.
  • The C-terminal region of p53, including acetylation, is essential for this downregulation.
  • p53 is recruited to the H ferritin promoter by NF-Y, despite the absence of direct p53-binding sites.
  • The p53-NF-Y interaction does not impede NF-Y's DNA-binding capability.

Conclusions:

  • The H ferritin gene is a novel p53-regulated gene, adding complexity to its transcriptional control.
  • p53, through interaction with NF-Y, plays a role in regulating H ferritin expression.
  • This finding highlights a new aspect of p53's function in cellular events triggered by DNA damage.

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