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Yeast As a Chassis for Developing Functional Assays to Study Human P53
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Yeast As a Chassis for Developing Functional Assays to Study Human P53

Published on: August 4, 2019

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Mutant p53 partners in crime

Michael P Kim1,2, Guillermina Lozano2

  • 1Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

Cell Death and Differentiation
|November 4, 2017
PubMed

Insights

Mutant p53 proteins alter cell function by interacting with other proteins, leading to gene expression changes. Understanding these context-specific interactions is key to developing therapies targeting mutant p53 gain-of-function activities.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Mutant p53 proteins significantly alter cellular behavior and function.
  • These alterations arise from interactions with intracellular proteins, influencing gene expression.
  • The specific protein interactions are highly dependent on cellular context, disease state, and environmental conditions.

Purpose of the Study:

  • To review proteins interacting with mutant p53 that activate gain-of-function (GOF) genes.
  • To emphasize the context-dependent nature of these interactions and GOF mechanisms.
  • To explore therapeutic strategies for targeting mutant p53 GOF.

Main Methods:

  • Literature review of proteins interacting with mutant p53.
  • Analysis of context dependency in mutant p53 protein-protein interactions.
  • Examination of gain-of-function mechanisms driven by mutant p53.

Main Results:

  • Identified various proteins that interact with mutant p53, contributing to GOF.
  • Highlighted that mutant p53 conformations dictate the specific protein-protein interactions.
  • Emphasized the significant influence of cellular context, disease, and environment on these interactions.

Conclusions:

  • Knowledge of mutant p53 interactions and their context dependency is crucial for therapeutic development.
  • Understanding GOF mechanisms provides avenues for blunting or ablating mutant p53 activity.
  • Translating insights into predicting and altering biologic activity for therapy remains a key challenge.

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