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Updated: Aug 9, 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

Repression of the MSP/MST-1 gene contributes to the antiapoptotic gain of function of mutant p53

A Zalcenstein1, L Weisz, P Stambolsky

  • 1Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.

Oncogene
|September 20, 2005
PubMed

Insights

Mutant p53 suppresses the expression of the MSP gene, a ligand for the RON receptor tyrosine kinase. This repression confers cancer cell resistance to death, suggesting a role for mutant p53 in oncogenesis.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cell Biology

Background:

  • Tumor-associated mutant p53 proteins can gain antiapoptotic functions, aiding tumor cell survival.
  • The MSP gene encodes a ligand for the RON receptor tyrosine kinase, involved in cellular signaling.
  • Aberrant RON signaling is linked to tumor progression, yet reduced MSP expression is observed in many cancers.

Purpose of the Study:

  • To investigate the regulatory relationship between mutant p53 and MSP gene expression.
  • To determine the functional consequences of MSP downregulation by mutant p53 on cancer cell survival.

Main Methods:

  • Analysis of mutant p53's association with the MSP gene promoter.
  • Measurement of MSP mRNA and secreted protein levels following mutant p53 interaction.
  • Assessment of cell death resistance in cancer cells with downregulated MSP expression.

Main Results:

  • Mutant p53 directly represses the transcriptional activity of the MSP gene promoter.
  • This repression leads to decreased MSP mRNA and secreted protein levels.
  • Downregulation of MSP confers resistance to etoposide-induced cell death in lung carcinoma cells.

Conclusions:

  • Mutant p53-mediated repression of MSP gene expression contributes to cancer cell survival.
  • This mechanism may play a cell type-specific role in oncogenesis.
  • Findings reconcile the pro-survival role of RON with reduced MSP levels in cancer.

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