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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

Tumor protein translationally controlled 1 is a p53 target gene that promotes cell survival

Weimin Chen1, Huihui Wang, Shasha Tao

  • 1Department of Pharmacology & Toxicology, College of Pharmacy, University of Arizona, Tucson, AZ, USA.

Cell Cycle (Georgetown, Tex.)
|September 27, 2013
PubMed

Insights

Tumor suppressor p53 directly regulates Tpt1 gene expression, which helps cells survive oxidative stress. This p53-Tpt1 link is lost in lung tumors, suggesting new cancer intervention strategies.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Genetics

Background:

  • The tumor suppressor p53 is crucial for maintaining genome stability through regulating target genes involved in cell cycle arrest, apoptosis, and antioxidant responses.
  • While many p53 targets are known, ongoing research continuously identifies novel genes regulated by p53.

Purpose of the Study:

  • To investigate Tpt1 as a direct target gene of the tumor suppressor p53.
  • To elucidate the functional role of p53-mediated Tpt1 regulation in cellular responses to oxidative stress.
  • To examine the correlation between p53 and Tpt1 expression in normal and cancerous lung tissues and cell lines.

Main Methods:

  • Identification of a p53-responsive element in the promoter region of the mouse Tpt1 gene.
  • Analysis of p53-dependent Tpt1 transcription.
  • Assessment of Tpt1's role in mitigating oxidative stress, apoptosis, and promoting cell survival.
  • Correlation analysis of p53 and Tpt1 expression in lung tissues and cell lines with varying p53 status.

Main Results:

  • Tpt1 was identified as a direct transcriptional target of p53.
  • p53 upregulates Tpt1 expression, which confers resistance to hydrogen peroxide-induced oxidative stress, reduces apoptosis, and enhances cell survival.
  • A positive correlation between p53 and Tpt1 expression was observed in normal lung tissues and wild-type p53 lung cell lines, but not in lung tumors or mutated p53 cell lines.

Conclusions:

  • Tpt1 is a novel, direct target gene of tumor suppressor p53, contributing to cellular defense against oxidative stress.
  • The loss of the positive correlation between p53 and Tpt1 in lung tumors highlights a potential mechanism of cancer development and chemoresistance.
  • The findings suggest Tpt1 as a potential target for novel cancer prevention and therapeutic intervention strategies.
Keywords:
TCTPTpt1cancerp53

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