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Activation of p53 by protein inhibitor of activated Stat1 (PIAS1)

Tamar Megidish1, Juliana H Xu, C Wilson Xu

  • 1Molecular Pharmacology Program, Sloan-Kettering Institute, Cornell University, New York, New York 10021, USA.

The Journal of Biological Chemistry
|January 15, 2002
PubMed

Insights

Protein inhibitor of activated Stat1 (PIAS1) interacts with the tumor suppressor p53, activating its gene expression. This novel PIAS1 activation of p53 promotes cell cycle arrest and apoptosis.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biochemistry

Background:

  • The tumor suppressor protein p53 is a critical transcription factor regulating cell cycle arrest and apoptosis.
  • Understanding p53 regulation is crucial for cancer research and therapeutic development.

Purpose of the Study:

  • To investigate the interaction between protein inhibitor of activated Stat1 (PIAS1) and p53.
  • To determine if PIAS1 influences p53 transcriptional activity.

Main Methods:

  • Yeast two-hybrid assays to detect protein-protein interactions.
  • Co-immunoprecipitation in mammalian cells to confirm endogenous interactions.
  • Functional assays involving ectopic PIAS1 expression in various cell lines, including p53-deficient cells.
  • Analysis of p53-mediated gene expression (e.g., p21) and cell cycle progression.

Main Results:

  • PIAS1 directly interacts with both the tetramerization and C-terminal regulatory domains of p53.
  • Endogenous PIAS1 and p53 proteins associate within mammalian cells.
  • Ectopic PIAS1 expression enhances p53-mediated transcriptional activity across multiple cell types.
  • PIAS1 induces p53-dependent expression of p21 and G1 cell cycle arrest.
  • PIAS1's activation of p53 does not require its RING-finger domain, suggesting sumoylation is not essential for this function.

Conclusions:

  • PIAS1 is identified as a novel activator of the tumor suppressor p53.
  • PIAS1 enhances p53's ability to induce target gene expression and promote cell cycle arrest.
  • These findings reveal a new regulatory mechanism for p53 function.

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