Related Experiment Video

Updated: Jan 15, 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

Published on: December 30, 2025

21

Acetylation promotes mutant (MUT) TP53-HSPA8 and HSPA8-BAG3 interactions, facilitating MUT TP53 lysosomal degradation

Michele Di Crosta1, Francesca Chiara Ragone1, Rossella Benedetti1

  • 1Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy.

Autophagy
|October 16, 2025
PubMed

Insights

Valproic acid (VPA) triggers acetylation, promoting the lysosomal degradation of mutant TP53 via chaperone-assisted selective autophagy (CASA). This finding reveals a new therapeutic strategy targeting aggressive tumors expressing mutant TP53.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Mutant TP53 (MUT TP53) proteins possess oncogenic properties, making them critical targets in anticancer therapy.
  • Valproic acid (VPA) is known to downregulate MUT TP53 expression in various tumor cells, but the underlying mechanisms require elucidation.

Purpose of the Study:

  • To investigate the molecular mechanisms by which VPA induces the degradation of MUT TP53.
  • To explore the role of acetylation and autophagy in VPA-mediated MUT TP53 clearance.

Main Methods:

  • The study utilized cell-based assays to examine the effects of VPA on MUT TP53 expression and degradation.
  • Protein interaction studies, including co-immunoprecipitation, were performed to identify interacting partners in the degradation pathway.
  • Acetylation levels of MUT TP53 and associated proteins were analyzed.

Main Results:

  • VPA induces acetylation of MUT TP53, which promotes its degradation through the lysosomal pathway.
  • This degradation preferentially occurs via chaperone-assisted selective autophagy (CASA).
  • VPA-induced acetylation enhances the interaction of MUT TP53 with chaperones STUB1, HSPB8, and HSPA8, facilitating its recruitment into the CASA pathway.

Conclusions:

  • Acetylation is a key mechanism by which VPA leads to the selective lysosomal clearance of MUT TP53.
  • The findings highlight the CASA pathway as crucial for VPA-mediated degradation of MUT TP53.
  • Targeting this acetylation-dependent degradation pathway presents a potential therapeutic vulnerability for aggressive tumors expressing MUT TP53.
Keywords:
AcetylationMUT TP53VPAlysosomesmacroautophagypancreatic cancer

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