p73 and p63 Regulate the Expression of Fibroblast Growth Factor Receptor 3

Biochem Biophys Res Commun. 2010 Apr 9;394(3):824-8. doi: 10.1016/j.bbrc.2010.03.084. Epub 2010 Mar 16.

Abstract

p53, p63 and p73 make a family of transcription factors that play a vital role in development and cancer. All p53 family members have more than one promoter producing Transactivating (TA) and Dominant Negative (DeltaN) isoforms and their mRNAs are subjected to extensive splicing at 3' end to produce multiple protein products. p53 is usually inactivated by point mutations during tumorigenesis, whereas the expression levels and p63 and p73 are modulated to give tumor cells a selective advantage. In this study, aiming to find novel targets of the p53 family members, we identified FGFR3 as a gene transcriptionally controlled by p63 and p73. FGFR3 has been implicated in development and tumor biology as activating mutations of this gene was described in skeletal disorders, non-invasive skin conditions and superficial bladder cancers. We found that TAp73, TAp63 and DeltaNp63 was capable of inducing FGFR3. siRNA mediated downregulation of DeltaNp63 decreased endogenous FGFR3 protein levels. Our findings of this new link between p53 family proteins and FGFR3 may help understanding the transition of superficial bladder cancers to an invasive phenotype.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Cell Line, Tumor
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Molecular Sequence Data
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Receptor, Fibroblast Growth Factor, Type 3 / genetics*
  • Skin Neoplasms / genetics
  • Skin Neoplasms / pathology*
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*
  • Transcription Factors
  • Transcriptional Activation*
  • Tumor Protein p73
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism*
  • Urinary Bladder Neoplasms / genetics
  • Urinary Bladder Neoplasms / pathology*

Substances

  • DNA-Binding Proteins
  • Nuclear Proteins
  • TP63 protein, human
  • Trans-Activators
  • Transcription Factors
  • Tumor Protein p73
  • Tumor Suppressor Proteins
  • p73 protein, human
  • Receptor, Fibroblast Growth Factor, Type 3