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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

Tumour suppressor p53 inhibits human fibroblast growth factor 2 expression by a post-transcriptional mechanism

B Galy1, L Créancier, C Zanibellato

  • 1Institut National de la Santé et de la Recherche Médicale U397, Endocrinologie et Communication Cellulaire, Institut Fédératif de Recherche Louis Bugnard, CHU Rangueil, 31403 Toulouse Cedex 04, France.

Oncogene
|April 21, 2001
PubMed

Insights

The tumor suppressor p53 inhibits the expression of fibroblast growth factor-2 (FGF-2) at the translational level. This novel mechanism, independent of gene transactivation, blocks FGF-2

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Cancer Research

Background:

  • Fibroblast growth factor-2 (FGF-2) is a potent mitogen and angiogenic factor.
  • FGF-2 expression is primarily regulated post-transcriptionally.
  • Constitutive upregulation of FGF-2 in cancer cells suggests a role for tumor suppressors in its regulation.

Purpose of the Study:

  • To investigate the post-transcriptional effects of the tumor suppressor p53 on FGF-2 expression.
  • To elucidate the mechanism by which p53 influences FGF-2 translation.
  • To determine if p53's inhibitory effect on FGF-2 is linked to its transactivation activity.

Main Methods:

  • Human primary skin fibroblast culture and transfection.
  • Reporter gene assays using chimeric FGF--CAT proteins.
  • RNAse mapping to assess mRNA accumulation.
  • Site-directed mutagenesis of p53.

Main Results:

  • Endogenous p53 expression inversely correlated with FGF-2 mRNA translatability in a cell-density-dependent manner.
  • Wild-type p53 significantly inhibited FGF--CAT protein expression.
  • p53 mediated translational inhibition via the FGF-2 mRNA leader sequence, independent of mRNA accumulation.
  • p53's inhibitory activity was independent of its DNA-binding and transactivating domains, and not mimicked by p73 or p21/waf.

Conclusions:

  • p53 exerts a novel post-transcriptional inhibitory effect on FGF-2 expression.
  • This inhibition occurs at the translational level and is mediated by the FGF-2 mRNA leader.
  • p53's tumor suppressive function may involve blocking the expression of key pro-proliferative and angiogenic genes like FGF-2 through a non-canonical mechanism.

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