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Updated: Aug 8, 2026

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 regulates human insulin-like growth factor II gene expression through active P4 promoter in rhabdomyosarcoma

L Zhang1, Q Zhan, S Zhan

  • 1Molecular Oncology Section, Pediatric Oncology Branch, National Cancer Institute, Bethesda, MD 20892-1928, USA.

DNA and Cell Biology
|March 21, 1998
PubMed

Insights

The tumor suppressor p53 inhibits the insulin-like growth factor II (IGFII) gene, a key driver of tumor growth. This study reveals p53 suppresses IGFII P4 promoter activity through direct binding, impacting tumor cell proliferation.

Area of Science:

  • Molecular Biology
  • Oncology
  • Genetics

Background:

  • The human insulin-like growth factor II (IGFII) gene is upregulated in many tumors, promoting cancer cell proliferation.
  • Tumor cells often exhibit defects in the p53 tumor suppressor gene.
  • Previous work showed p53 inhibits the IGFII P3 promoter via interference with TBP binding.

Purpose of the Study:

  • To investigate the effect of wild-type p53 expression on the IGFII P4 promoter in rhabdomyosarcoma cell lines.
  • To elucidate the mechanism by which p53 regulates IGFII P4 promoter activity.

Main Methods:

  • Utilized rhabdomyosarcoma cell lines with mutant p53.
  • Introduced wild-type p53 expression into these cell lines.
  • Assessed IGFII P4 promoter activity and IGFII mRNA levels.
  • Performed p53 binding assays to the P4 promoter region.

Main Results:

  • Wild-type p53 expression reduced IGFII P4 promoter activity by 5-fold.
  • IGFII mRNA levels derived from the P4 promoter were significantly decreased.
  • p53 directly bound to the P4 proximal promoter element, independent of a consensus binding site.
  • The mechanism of P4 inhibition differs from p53's effect on the P3 promoter.

Conclusions:

  • p53 directly inhibits IGFII P4 promoter activity through a novel binding mechanism.
  • This regulation pathway is distinct from p53's previously described inhibition of the IGFII P3 promoter.
  • Findings provide further evidence for cross-talk between IGF and p53 signaling pathways in cancer.

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