Δ133p53β isoform pro-invasive activity is regulated through an aggregation-dependent mechanism in cancer cells

Nikola Arsic, Tania Slatter, Gilles Gadea, Etienne Villain, Aurelie Fournet, Marina Kazantseva, Frédéric Allemand, Nathalie Sibille, Martial Seveno, Sylvain de Rossi, Sunali Mehta, Serge Urbach, Jean Christophe Bourdon, Pau Bernado, Andrey V. Kajava, Antony Braithwaite, Pierre Roux (Lead / Corresponding author)

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Abstract

The p53 isoform, Δ133p53β, is critical in promoting cancer. Here we report that Δ133p53β activity is regulated through an aggregation-dependent mechanism. Δ133p53β aggregates were observed in cancer cells and tumour biopsies. The Δ133p53β aggregation depends on association with interacting partners including p63 family members or the CCT chaperone complex. Depletion of the CCT complex promotes accumulation of Δ133p53β aggregates and loss of Δ133p53β dependent cancer cell invasion. In contrast, association with p63 family members recruits Δ133p53β from aggregates increasing its intracellular mobility. Our study reveals novel mechanisms of cancer progression for p53 isoforms which are regulated through sequestration in aggregates and recruitment upon association with specific partners like p63 isoforms or CCT chaperone complex, that critically influence cancer cell features like EMT, migration and invasion.

Original languageEnglish
Article number5463
Number of pages18
JournalNature Communications
Volume12
DOIs
Publication statusPublished - 15 Sep 2021

Keywords

  • Cancer
  • Cell Biology

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