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

Nikola Arsic (1) , Tania Slatter (2) , Gilles Gadea (3, 4) , Etienne Villain (1) , Aurelie Fournet (5) , Marina Kazantseva (2) , Frédéric Allemand (5) , Nathalie Sibille (5) , Martial Séveno (6) , Sylvain de Rossi (6) , Sunali Mehta (2) , S Urbach (7) , Jean-Christophe Bourdon (8) , Pau Bernado (5) , Andrey Kajava (1, 9) , Antony Braithwaite (2) , Pierre Roux (1)

1 CRBM - Centre de recherche en Biologie cellulaire de Montpellier
2 University of Otago [Dunedin, Nouvelle-Zélande]
3 UR - Université de La Réunion
4 CYROI - Cyclotron Réunion Océan Indien
5 CBS - Centre de Biochimie Structurale [Montpellier]
6 BCM - BioCampus
7 IGF - Institut de Génomique Fonctionnelle
8 Ninewells Hospital and Medical School [Dundee]
9 IBC - Institut de Biologie Computationnelle

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.

Domaines: Biologie cellulaire

Nikola Arsic, Tania Slatter, Gilles Gadea, Etienne Villain, Aurelie Fournet, et al.. Δ133p53β isoform pro-invasive activity is regulated through an aggregation-dependent mechanism in cancer cells. Nature Communications, 2021, 12 (1), pp.5463. ⟨10.1038/s41467-021-25550-2⟩. ⟨hal-03346748⟩