Regulation of apoptosis by p53-inducible transmembrane protein containing sushi domain

Hongyan Cui1, Hiroki Kamino, Yasuyuki Nakamura

  • 1Cancer Medicine and Biophysics Division, National Cancer Center Research Institute, Chuo-ku, Tokyo 104-0045, Japan.

Oncology Reports
|September 30, 2010
PubMed

Insights

The tumor suppressor p53 activates the TMPS gene, a novel target. TMPS promotes apoptosis in cancer cells, highlighting its role in DNA damage response.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Genetics

Background:

  • The p53 tumor suppressor is crucial for cellular response to DNA damage, preventing malignant transformation.
  • Identifying novel p53 target genes is essential for understanding its tumor-suppressive functions.

Purpose of the Study:

  • To identify and characterize novel p53 target genes involved in DNA damage response.
  • To investigate the role of the transmembrane protein containing sushi domain (TMPS) gene as a p53 target.

Main Methods:

  • cDNA microarray analysis to identify potential p53 targets.
  • Reporter assays and chromatin immunoprecipitation (ChIP) to confirm p53 binding and transactivation.
  • Apoptosis assays (caspase activation) and mouse models (p53+/+ vs. p53-/-) to assess TMPS function.

Main Results:

  • TMPS was identified as a novel p53 target gene.
  • p53 directly binds to and transactivates the TMPS gene in response to genotoxic stress.
  • TMPS overexpression induces apoptosis via caspase activation in cancer cell lines.
  • TMPS expression is induced by DNA damage in a p53-dependent manner in mouse tissues.

Conclusions:

  • TMPS is a novel p53 target gene regulated by p53 under genotoxic stress.
  • TMPS plays a role in p53-dependent apoptosis, contributing to tumor suppression.
  • TMPS represents a potential therapeutic target in cancer treatment.

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