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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

Ets1 is required for p53 transcriptional activity in UV-induced apoptosis in embryonic stem cells

Dakang Xu1, Trevor J Wilson, David Chan

  • 1Centre for Functional Genomics and Human Disease, Monash Institute of Reproduction and Development, Monash University, 246 Clayton, Clayton, Victoria 3168, Australia.

The EMBO Journal
|July 30, 2002
PubMed

Insights

Ets1 is crucial for UV-induced apoptosis in embryonic stem (ES) cells by enabling p53 to activate target genes. This finding highlights Ets1

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Stem Cell Research

Background:

  • Embryonic stem (ES) cells possess a p53-dependent apoptosis pathway to eliminate damaged cells.
  • UV radiation triggers apoptosis in ES cells, a process critical for genomic integrity.

Purpose of the Study:

  • To investigate the role of Ets1 in UV-induced apoptosis and p53 transcriptional activity in mouse ES cells.
  • To elucidate the molecular mechanism by which Ets1 influences p53 function.

Main Methods:

  • Comparison of UV-induced apoptosis in wild-type, Ets1(-/-), and p53 null ES cells.
  • Analysis of p53-regulated gene expression (mRNA and protein) via quantitative PCR and Western blotting.
  • Electrophoretic mobility shift assays (EMSA), co-immunoprecipitation, and chromatin immunoprecipitation (ChIP) to assess protein-DNA interactions and complex formation.

Main Results:

  • Ets1(-/-) ES cells exhibit impaired UV-induced apoptosis, similar to p53 null ES cells.
  • UV induction of p53 target genes (mdm2, perp, cyclin G, bax) is significantly reduced in Ets1(-/-) ES cells at both mRNA and protein levels.
  • Ets1 is essential for p53's transactivation of target genes, CBP/p53 complex formation, stable p53-DNA binding, and histone acetyltransferase activity.

Conclusions:

  • Ets1 is a critical component of the UV-responsive p53 transcriptional activation complex in ES cells.
  • Ets1 facilitates p53-dependent gene transactivation, suggesting a role in cellular compartment-specific p53 activity.

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