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Phosphorylation of p53 by TAF1 inactivates p53-dependent transcription in the DNA damage response

Yong Wu1, Joy C Lin1, Landon G Piluso1

  • 1Department of Biochemistry, University of California, Riverside, Riverside, CA 92521, USA.

Molecular Cell
|December 3, 2013
PubMed

Insights

TAF1 phosphorylates p53, turning off p21 gene expression after DNA damage. Cellular ATP levels act as a switch, controlling this process and indicating TAF1 is an ATP sensor.

Area of Science:

  • Molecular Biology
  • Cellular Biology
  • Biochemistry

Background:

  • p53 activation is crucial for DNA damage response.
  • Mechanisms for deactivating p53 target genes are not well understood.

Purpose of the Study:

  • To elucidate the mechanism of p53 target gene inactivation after DNA damage.
  • To identify the role of TAF1 and cellular ATP levels in this process.

Main Methods:

  • Phosphorylation assays
  • Chromatin immunoprecipitation sequencing (ChIP-seq)
  • Analysis of cellular ATP levels

Main Results:

  • TAF1 phosphorylates p53 at Thr55, causing p53 to detach from the p21 promoter.
  • Cellular ATP levels regulate TAF1 activity, functioning as a molecular switch.
  • DNA damage induces ATP depletion, reducing TAF1 activity and increasing p21 expression.
  • ATP recovery restores TAF1 activity, leading to p53 dissociation and p21 inactivation.
  • Genome-wide ChIP-seq shows p53 dissociation from promoters upon DNA damage recovery.

Conclusions:

  • TAF1 acts as a cellular ATP sensor, regulating p53 activity.
  • ATP-dependent TAF1 phosphorylation of p53 is a key mechanism for inactivating p53 target genes.
  • This mechanism is likely general across multiple promoters during DNA damage response recovery.

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