p73 and p63 regulate the expression of fibroblast growth factor receptor 3

A Emre Sayan1, Barbara D'Angelo, Berna S Sayan

  • 1MRC Toxicology Unit, Lancaster Road, Hodgkin Building, Leicester LE1 9HN, UK. aes16@le.ac.uk

Insights

The p53 family of transcription factors, including p63 and p73, regulates FGFR3 gene expression. This discovery offers insights into how superficial bladder cancers may become invasive.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Genetics

Background:

  • The p53, p63, and p73 protein family are crucial transcription factors in development and cancer.
  • These proteins exhibit multiple isoforms (Transactivating and Dominant Negative) and undergo extensive mRNA splicing.
  • While p53 is often inactivated by mutation, p63 and p73 expression is modulated for tumor cell advantage.

Purpose of the Study:

  • To identify novel target genes regulated by the p53 family members (p53, p63, p73).
  • To investigate the role of p63 and p73 in controlling Fibroblast Growth Factor Receptor 3 (FGFR3) expression.

Main Methods:

  • Investigated transcriptional control of FGFR3 by p63 and p73.
  • Utilized siRNA-mediated downregulation to assess the impact of DeltaNp63 on endogenous FGFR3 protein levels.

Main Results:

  • FGFR3 was identified as a gene transcriptionally controlled by p63 and p73.
  • TAp73, TAp63, and DeltaNp63 isoforms were found to induce FGFR3 expression.
  • Downregulation of DeltaNp63 using siRNA led to decreased endogenous FGFR3 protein levels.

Conclusions:

  • Established a novel regulatory link between p53 family proteins (p63, p73) and FGFR3.
  • Findings may elucidate the mechanism driving the transition of superficial bladder cancers to an invasive phenotype.
  • Highlights the role of FGFR3 in development and tumor biology, with implications for skeletal disorders and skin conditions.

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