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Purification of Ubiquitinated p53 Proteins from Mammalian Cells
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Purification of Ubiquitinated p53 Proteins from Mammalian Cells

Published on: March 21, 2022

The prolyl-isomerase Pin1 activates the mitochondrial death program of p53

G Sorrentino1, M Mioni, C Giorgi

  • 1Laboratorio Nazionale CIB, Area Science Park, Padriciano 99, 34149 Trieste, Italy.

Cell Death and Differentiation
|September 1, 2012
PubMed

Insights

The prolyl-isomerase Pin1 (peptidylprolyl cis/trans isomerase, NIMA-interacting 1) protein is essential for stress-induced p53 protein localization to mitochondria. Pin1 is required for p53-mediated mitochondrial apoptosis, impacting cancer treatment strategies.

Area of Science:

  • Cellular Biology
  • Molecular Biology
  • Biochemistry

Background:

  • The tumor suppressor protein p53 (p53) initiates a mitochondrial death pathway under stress, preceding transcriptional apoptosis.
  • This pathway aids tumor suppression and cancer cell death induced by various drugs and p53-reactivating molecules.

Purpose of the Study:

  • To investigate the role of prolyl-isomerase Pin1 (peptidylprolyl cis/trans isomerase, NIMA-interacting 1) in the p53-mediated mitochondrial death pathway.
  • To elucidate how Pin1 influences p53's phosphorylation-dependent conformational changes and pro-apoptotic activity.

Main Methods:

  • In vitro and in vivo experiments to assess p53 localization to mitochondria.
  • Analysis of p53 phosphorylation on Ser46 by homeodomain interacting protein kinase 2.
  • Investigation of Pin1's role in p53 monoubiquitination and mitochondrial trafficking.
  • Evaluation of Pin1's requirement for RITA-induced mitochondrial apoptosis.

Main Results:

  • Pin1 promotes stress-induced p53 localization to mitochondria.
  • Pin1 stimulates p53 monoubiquitination, a mitochondrial trafficking signal, following phosphorylation by homeodomain interacting protein kinase 2.
  • Pin1 is crucial for the induction of mitochondrial apoptosis by the p53-activating molecule RITA.

Conclusions:

  • Pin1 acts as a key transducer of p53's pro-apoptotic function by facilitating its mitochondrial translocation.
  • These findings highlight Pin1's critical role in p53-mediated cell death and suggest its potential as a therapeutic target in p53-expressing tumors.

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