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

Autor: Arsic N; Université de Montpellier, Centre de Recherche en Biologie Cellulaire de Montpellier (CRBM) CNRS, UMR 5237, Montpellier, France.; Université de Montpellier, Montpellier, France., Slatter T; Department of Pathology, University of Otago, Dunedin, New Zealand., Gadea G; Université de la Réunion, Unité Mixte 134 Processus Infectieux en Milieu Insulaire Tropical, INSERM Unité 1187, CNRS Unité Mixte de Recherche 9192, IRD Unité Mixte de Recherche 249. Plateforme Technologique CYROI, Sainte Clotilde, France., Villain E; Université de Montpellier, Centre de Recherche en Biologie Cellulaire de Montpellier (CRBM) CNRS, UMR 5237, Montpellier, France.; Université de Montpellier, Montpellier, France., Fournet A; Université de Montpellier, Montpellier, France.; Centre de Biochimie Structurale (CBS), INSERM, CNRS, 29 rue de Navacelles, Montpellier, France., Kazantseva M; Department of Pathology, University of Otago, Dunedin, New Zealand., Allemand F; Université de Montpellier, Montpellier, France.; Centre de Biochimie Structurale (CBS), INSERM, CNRS, 29 rue de Navacelles, Montpellier, France., Sibille N; Université de Montpellier, Montpellier, France.; Centre de Biochimie Structurale (CBS), INSERM, CNRS, 29 rue de Navacelles, Montpellier, France., Seveno M; Université de Montpellier, Montpellier, France.; BioCampus Montpellier, CNRS, INSERM, Montpellier, France., de Rossi S; MRI, UMS BioCampus Montpellier, CNRS, INSERM, Université de Montpellier, Montpellier, France., Mehta S; Department of Pathology, University of Otago, Dunedin, New Zealand., Urbach S; Université de Montpellier, Montpellier, France.; IGF, CNRS, INSERM, Montpellier, France., Bourdon JC; Dundee Cancer Centre, University of Dundee, Ninewells Hospital and Medical School, Dundee, UK., Bernado P; Université de Montpellier, Montpellier, France.; Centre de Biochimie Structurale (CBS), INSERM, CNRS, 29 rue de Navacelles, Montpellier, France., Kajava AV; Université de Montpellier, Centre de Recherche en Biologie Cellulaire de Montpellier (CRBM) CNRS, UMR 5237, Montpellier, France.; Université de Montpellier, Montpellier, France.; Institut de Biologie Computationnelle, Montpellier, France., Braithwaite A; Department of Pathology, University of Otago, Dunedin, New Zealand., Roux P; Université de Montpellier, Centre de Recherche en Biologie Cellulaire de Montpellier (CRBM) CNRS, UMR 5237, Montpellier, France. pierre.roux@crbm.cnrs.fr.; Université de Montpellier, Montpellier, France. pierre.roux@crbm.cnrs.fr.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2021 Sep 15; Vol. 12 (1), pp. 5463. Date of Electronic Publication: 2021 Sep 15.
DOI: 10.1038/s41467-021-25550-2
Abstrakt: 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.
(© 2021. The Author(s).)
Databáze: MEDLINE
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