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Yeast As a Chassis for Developing Functional Assays to Study Human P53
14:57

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

Published on: August 4, 2019

Structural biology of the tumor suppressor p53

Andreas C Joerger1, Alan R Fersht

  • 1Medical Research Council Centre for Protein Engineering, Cambridge, United Kingdom. acj2@mrc-lmb.cam.ac.uk

Annual Review of Biochemistry
|April 16, 2008
PubMed

Insights

The tumor suppressor protein p53, a guardian of the genome, regulates genes for cell cycle control, senescence, and apoptosis. This review explores p53

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Structural Biology

Background:

  • The tumor suppressor protein p53 is crucial for cellular stress response.
  • p53 controls genes involved in cell cycle arrest, senescence, and apoptosis.
  • Its function is mediated by a combination of structured and disordered domains.

Purpose of the Study:

  • To review the structural complexity of p53.
  • To elucidate mechanisms of p53 inactivation in cancer.
  • To discuss therapeutic strategies for restoring p53 function.

Main Methods:

  • Literature review of structural and functional studies on p53.
  • Analysis of cancer-associated mutations affecting p53.
  • Overview of emerging pharmacological approaches targeting p53.

Main Results:

  • p53's modular structure, including intrinsically disordered regions, is key to its function.
  • Cancer-related mutations often compromise p53's structural integrity and activity.
  • Pharmacological strategies aim to reactivate mutant or stabilize wild-type p53.

Conclusions:

  • p53's intricate structure underlies its role as a master regulator.
  • Understanding p53 inactivation is vital for developing effective cancer therapies.
  • p53 serves as a model for studying modular proteins and mutation effects.

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