A p53 amino-terminal nuclear export signal inhibited by DNA damage-induced phosphorylation

Y Zhang1, Y Xiong

  • 1Lineberger Comprehensive Cancer Center, Department of Biochemistry and Biophysics, and Program in Molecular Biology and Biotechnology, University of North Carolina at Chapel Hill, NC 27599-7295, USA.

Science (New York, N.Y.)
|June 9, 2001
PubMed

Insights

The tumor suppressor p53 protein

Area of Science:

  • Molecular Biology
  • Cellular Biology
  • Cancer Research

Background:

  • The p53 protein is a crucial tumor suppressor.
  • MDM2 negatively regulates p53 activity through inhibition and degradation.
  • Understanding p53 regulation is vital for cancer therapy.

Purpose of the Study:

  • To identify novel regulatory mechanisms of p53.
  • To investigate the role of p53 phosphorylation in its regulation.
  • To elucidate how DNA damage impacts p53 localization and activity.

Main Methods:

  • Identification of a novel nuclear export signal (NES) in p53.
  • Phosphorylation site analysis of p53 residues.
  • Investigation of p53 nuclear export dynamics following DNA damage.

Main Results:

  • A novel N-terminal NES (residues 11-27) in p53 was identified.
  • This NES contains two serine residues phosphorylated upon DNA damage.
  • Phosphorylation of Serine-15 in p53, induced by UV irradiation, inhibited nuclear export.
  • DNA damage-induced phosphorylation of p53 may prevent its export and MDM2 binding.

Conclusions:

  • DNA damage-induced phosphorylation of p53 inhibits its nuclear export.
  • This inhibition, along with reduced MDM2 binding, contributes to optimal p53 activation.
  • These findings reveal a new layer of p53 regulation critical for cellular response to DNA damage.

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