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Updated: Jun 22, 2026

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death
09:18

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death

Published on: December 27, 2016

PAC1 phosphatase is a transcription target of p53 in signalling apoptosis and growth suppression

Yuxin Yin1, Yu-Xin Liu, Yan J Jin

  • 1Department of Radiation Oncology, College of Physicians and Surgeons, Columbia University, 630 West 168th Street, New York, New York 10032, USA.

Nature
|April 4, 2003
PubMed

Insights

The tumor suppressor p53 activates the phosphatase PAC1 (dual specificity phosphatase 2) during apoptosis. PAC1 is essential for p53-mediated apoptosis and tumor suppression, revealing a new gene regulation mechanism.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Cancer Research

Background:

  • The tumor suppressor protein p53 regulates cellular processes via transcriptional control of target genes.
  • PAC1 (phosphatase of activated cells 1), also known as DUSP2, is a dual phosphatase inactivating MAP kinases.

Purpose of the Study:

  • To investigate the role of p53 in regulating PAC1 transcription.
  • To elucidate the mechanism of p53-mediated apoptosis involving PAC1.
  • To explore PAC1's function in tumor suppression.

Main Methods:

  • Analysis of PAC1 promoter activity and p53 binding.
  • Use of small interfering RNA (siRNA) to reduce PAC1 expression.
  • Overexpression studies of PAC1.
  • Measurement of MAP kinase activity.

Main Results:

  • p53 directly activates PAC1 transcription by binding to a palindromic site in its promoter.
  • PAC1 induction by p53 occurs under serum deprivation and oxidative stress, leading to apoptosis.
  • siRNA-mediated reduction of PAC1 inhibits p53-induced apoptosis, while PAC1 overexpression enhances apoptosis and suppresses tumor formation.
  • p53 activation inhibits MAP kinase activity, and PAC1 is necessary and sufficient for this process.

Conclusions:

  • p53 regulates PAC1 transcription through a novel binding site under specific stress conditions.
  • PAC1 is a key mediator of p53-dependent apoptosis and tumor suppression.
  • The identification of a palindromic p53-binding site offers insights into p53's gene regulatory mechanisms.
Keywords:
Non-programmatic

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