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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

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Alternative Mechanisms of p53 Action During the Unfolded Protein Response

Leïla T S Fusée1, Mónica Marín2, Robin Fåhraeus1,3,4,5

  • 1INSERM U1162, 27 rue Juliette Dodu, 75010 Paris, France.

Cancers
|February 14, 2020
PubMed

Insights

The tumor suppressor p53 protein has an isoform, p47, induced by Endoplasmic Reticulum stress. This isoform, p47, helps control cell homeostasis during the Unfolded Protein Response (UPR).

Area of Science:

  • Molecular Biology
  • Cellular Biology
  • Cancer Research

Background:

  • The tumor suppressor protein p53 regulates cellular stress responses, primarily through its function as a transcription factor.
  • p53 controls critical cellular events including cell cycle progression, DNA repair, and apoptosis.
  • The precise integration of signaling cascades by p53 remains an area of active investigation.

Purpose of the Study:

  • To investigate the role and expression of the p53 isoform p47 during the Unfolded Protein Response (UPR).
  • To elucidate how alternative translation initiation of p53 mRNA contributes to cellular homeostasis under Endoplasmic Reticulum stress.
  • To explore the therapeutic implications of modulating p53 isoform expression in cancer.

Main Methods:

  • Focus on the expression of the p53 isoform p47.
  • Analysis of alternative translation initiation of p53 mRNA.
  • Investigating p53 activity during global translation suppression in the UPR.

Main Results:

  • The p53 isoform p47 is specifically induced by the PERK kinase during the UPR.
  • Alternative translation initiation of p53 mRNA provides a condition-dependent mechanism to modulate p53 activity.
  • This mechanism differentiates p53 activity to maintain cell homeostasis during UPR.

Conclusions:

  • The expression of p47 offers a unique pathway for p53 to manage cellular homeostasis during Endoplasmic Reticulum stress and UPR.
  • Understanding p53 isoform regulation during UPR is crucial for comprehending cellular stress responses.
  • Targeting p53 translation and its isoforms presents potential therapeutic strategies for cancer treatment.
Keywords:
ER stressUPRmRNA translationp47p53

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