Related Experiment Video

Updated: Mar 13, 2026

Detection of Aggregation-Prone Behavior in Mutant P53 V157F Breast Cancer Cells Using Multipoint Thioflavin T Fluorescence
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Detection of Aggregation-Prone Behavior in Mutant P53 V157F Breast Cancer Cells Using Multipoint Thioflavin T Fluorescence

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DNAJA1 controls the fate of misfolded mutant p53 through the mevalonate pathway

Alejandro Parrales1, Atul Ranjan1, Swathi V Iyer1

  • 1Department of Cancer Biology, University of Kansas Medical Center, Kansas City, Kansas 66160, USA.

Nature Cell Biology
|October 28, 2016
PubMed

Insights

Statins degrade mutant p53 (mutp53) by disrupting its interaction with DNAJA1, offering a new therapeutic strategy. This cholesterol-lowering drug approach selectively targets cancer cells expressing mutp53.

Area of Science:

  • Oncology
  • Molecular Biology
  • Drug Discovery

Background:

  • Mutant p53 (mutp53) stabilization promotes tumor malignancy.
  • Mechanisms and therapies to destabilize mutp53 remain largely unexplored.

Purpose of the Study:

  • To identify therapeutic agents that destabilize mutp53.
  • To elucidate the molecular mechanisms underlying mutp53 degradation.

Main Methods:

  • High-throughput screening to identify mutp53 degradation inducers.
  • Investigating the role of the mevalonate pathway and DNAJA1 in mutp53 regulation.
  • Utilizing gene knockdown and overexpression techniques.

Main Results:

  • Statins identified as potent inducers of mutp53 degradation, with minimal impact on wild-type p53.
  • Statins preferentially inhibit growth of mutp53-expressing cancer cells.
  • Mevalonate pathway modulation and DNAJA1 knockdown promote CHIP-mediated mutp53 degradation.

Conclusions:

  • Statins represent a promising therapeutic strategy for targeting mutp53-driven cancers.
  • The mevalonate pathway-DNAJA1 axis is crucial for controlling mutp53 stability.
  • p53 status is a key determinant of statin efficacy in cancer therapy.

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