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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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The DNA-binding domain mediates both nuclear and cytosolic functions of p53

Ariele Viacava Follis1, Fabien Llambi2, Li Ou1

  • 1Department of Structural Biology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.

Nature Structural & Molecular Biology
|May 13, 2014
PubMed

Insights

The anti-apoptotic protein BCL-xL inhibits apoptosis by binding to p53 and other proteins. This study quanties BCL-xL

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biochemistry

Background:

  • The tumor suppressor p53 is a key regulator of apoptosis.
  • BCL-xL is an anti-apoptotic protein that inhibits p53.
  • The interaction between BCL-xL and p53 is crucial for regulating apoptosis under genotoxic stress.

Purpose of the Study:

  • To characterize the BCL-xL-p53 complex.
  • To determine the contribution of BCL-xL's interaction with p53 versus other BCL-2 family proteins in inhibiting UV-induced apoptosis.

Main Methods:

  • NMR spectroscopy to characterize the BCL-xL-p53 complex.
  • Mutagenesis to modulate the BCL-xL-p53 interaction.
  • Assessment of UV irradiation-induced apoptosis.

Main Results:

  • One-third of BCL-xL's anti-apoptotic activity is due to p53 sequestration.
  • Two-thirds of BCL-xL's anti-apoptotic activity is due to sequestration of pro-apoptotic BCL-2 family members.
  • Defined the relative contributions of BCL-xL interactions to apoptosis inhibition.

Conclusions:

  • Cytosolic p53 plays a defined role in UV irradiation-induced apoptosis.
  • The findings provide insights into p53-dependent apoptotic signaling pathways.
  • Offers potential targets for therapeutic interventions in cancer.

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