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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

Redefining the p53 response element

Bei Wang1, Ziwei Xiao, Ee Chee Ren

  • 1Laboratory of Immunogenetics, Singapore Immunology Network, A*STAR, 8A Biomedical Grove, Immunos, Singapore.

Proceedings of the National Academy of Sciences of the United States of America
|July 15, 2009
PubMed

Insights

The tumor suppressor p53

Area of Science:

  • Molecular Biology
  • Genetics
  • Cancer Research

Background:

  • The tumor suppressor p53 is a critical regulator of cellular events.
  • Predicting p53's transcriptional effects on target genes remains challenging despite numerous identified response elements (REs).

Purpose of the Study:

  • To systematically investigate the role of specific nucleotides within p53 REs.
  • To establish predictive rules for p53's transcriptional activation or repression.
  • To re-evaluate known p53 RE functions.

Main Methods:

  • Functional assays using p21 (activation) and Lasp1 (repression) targets.
  • Analysis of nucleotide sequences within the p53 RE, focusing on the CWWG motif and flanking regions.
  • Reassessment of 162 published p53 REs based on newly established rules.

Main Results:

  • A specific dinucleotide core within the CWWG motif dictates p53's activation or repression.
  • Flanking RRR and YYY triplets modulate p53 transcriptional activity.
  • 20/162 previously studied p53 REs were found to have erroneous functional attributions.
  • 39/162 p53 REs exhibit repressive functions, a higher proportion than previously recognized.

Conclusions:

  • Nucleotide sequence within p53 REs precisely determines transcriptional outcome (activation vs. repression).
  • Established predictive rules offer enhanced understanding of p53's role in cellular networks.
  • The prevalence of p53-mediated gene repression is significantly underestimated.

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