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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

The gut-enriched Kruppel-like factor (Kruppel-like factor 4) mediates the transactivating effect of p53 on the

W Zhang1, D E Geiman, J M Shields

  • 1Departments of Medicine and Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.

The Journal of Biological Chemistry
|April 6, 2000
PubMed

Insights

The tumor suppressor p53 induces cell cycle arrest by activating the p21(WAF1/Cip1) gene. Gut-enriched Krüppel-like factor (GKLF) is a novel mediator, essential for p53 to induce p21(WAF1/Cip1) expression during cellular stress.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Genomics

Background:

  • The tumor suppressor p53 is crucial for maintaining genomic stability.
  • p53 induces cell cycle arrest by activating the p21(WAF1/Cip1) gene.

Purpose of the Study:

  • To investigate the role of gut-enriched Krüppel-like factor (GKLF) in p53-mediated p21(WAF1/Cip1) induction.
  • To elucidate the mechanism by which GKLF interacts with p53 to regulate p21(WAF1/Cip1) expression.

Main Methods:

  • Methyl methanesulfonate (MMS) treatment to induce DNA damage.
  • Analysis of GKLF and p21(WAF1/Cip1) gene expression.
  • Reporter assays to study promoter activity.
  • Antisense GKLF oligonucleotides to block GKLF function.

Main Results:

  • GKLF and p21(WAF1/Cip1) are concurrently induced by DNA damage in a p53-dependent manner.
  • GKLF expression rise precedes p21(WAF1/Cip1) induction, suggesting a mediating role.
  • GKLF directly activates the p21(WAF1/Cip1) promoter via an Sp1-like cis-element.
  • p53 and GKLF synergistically induce p21(WAF1/Cip1) promoter activity.
  • Antisense GKLF oligonucleotides inhibit p21(WAF1/Cip1) production in response to p53 activation.

Conclusions:

  • GKLF is an essential mediator of p53 in the transcriptional induction of p21(WAF1/Cip1).
  • GKLF may be part of a novel pathway regulating cellular responses to stress.
  • These findings reveal a new mechanism for p53 in maintaining genomic stability.

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