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

doi:10.1038/s41467-021-25550-2

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 language	English
Article number	5463
Number of pages	18
Journal	Nature Communications
Volume	12
DOIs	https://doi.org/10.1038/s41467-021-25550-2
Publication status	Published - 15 Sept 2021

Keywords

Cancer
Cell Biology

ASJC Scopus subject areas

General Chemistry
General Biochemistry,Genetics and Molecular Biology
General Physics and Astronomy

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Final Published VersionFinal published version, 6.62 MBLicence: CC BY

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Arsic, N., Slatter, T., Gadea, G., Villain, E., Fournet, A., Kazantseva, M., Allemand, F., Sibille, N., Seveno, M., de Rossi, S., Mehta, S., Urbach, S., Bourdon, J. C., Bernado, P., Kajava, A. V., Braithwaite, A., & Roux, P. (2021). Δ133p53β isoform pro-invasive activity is regulated through an aggregation-dependent mechanism in cancer cells. Nature Communications, 12, Article 5463. https://doi.org/10.1038/s41467-021-25550-2

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

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.",

keywords = "Cancer, Cell Biology",

author = "Nikola Arsic and Tania Slatter and Gilles Gadea and Etienne Villain and Aurelie Fournet and Marina Kazantseva and Fr{\'e}d{\'e}ric Allemand and Nathalie Sibille and Martial Seveno and {de Rossi}, Sylvain and Sunali Mehta and Serge Urbach and Bourdon, {Jean Christophe} and Pau Bernado and Kajava, {Andrey V.} and Antony Braithwaite and Pierre Roux",

note = "Funding Information: This paper was supported by grant from INCa no. 2017-169, no. CNRS: 157944 N.A., P.R. and A.K. are supported by CNRS. A.W.B., T.S., S.M. and M.K. are supported by grants from the Health Research Council and Royal Society of New Zealand. P.R. is supported by INSERM. We acknowledge the imaging facility MRI, member of the national infrastructure France-BioImaging infrastructure supported by the French National Research Agency (ANR-10-INBS-04, «Investments for the future»). We thank V{\'e}ronique Gire and Philippe Fort (CRBM, CNRS, Montpellier) for helpful discussions. Mass spectrometry experiments were carried out using the facilities of the Montpellier Proteomics Platform (PPM, BioCampus Montpellier). We acknowledge Maurice Wilkins Centre for Molecular Biodiscovery for RNAseq funding. Publisher Copyright: {\textcopyright} 2021, The Author(s).",

year = "2021",

month = sep,

day = "15",

doi = "10.1038/s41467-021-25550-2",

language = "English",

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journal = "Nature Communications",

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Arsic, N, Slatter, T, Gadea, G, Villain, E, Fournet, A, Kazantseva, M, Allemand, F, Sibille, N, Seveno, M, de Rossi, S, Mehta, S, Urbach, S, Bourdon, JC, Bernado, P, Kajava, AV, Braithwaite, A & Roux, P 2021, 'Δ133p53β isoform pro-invasive activity is regulated through an aggregation-dependent mechanism in cancer cells', Nature Communications, vol. 12, 5463. https://doi.org/10.1038/s41467-021-25550-2

TY - JOUR

T1 - Δ133p53β isoform pro-invasive activity is regulated through an aggregation-dependent mechanism in cancer cells

AU - Arsic, Nikola

AU - Slatter, Tania

AU - Gadea, Gilles

AU - Villain, Etienne

AU - Fournet, Aurelie

AU - Kazantseva, Marina

AU - Allemand, Frédéric

AU - Sibille, Nathalie

AU - Seveno, Martial

AU - de Rossi, Sylvain

AU - Mehta, Sunali

AU - Urbach, Serge

AU - Bourdon, Jean Christophe

AU - Bernado, Pau

AU - Kajava, Andrey V.

AU - Braithwaite, Antony

AU - Roux, Pierre

N1 - Funding Information: This paper was supported by grant from INCa no. 2017-169, no. CNRS: 157944 N.A., P.R. and A.K. are supported by CNRS. A.W.B., T.S., S.M. and M.K. are supported by grants from the Health Research Council and Royal Society of New Zealand. P.R. is supported by INSERM. We acknowledge the imaging facility MRI, member of the national infrastructure France-BioImaging infrastructure supported by the French National Research Agency (ANR-10-INBS-04, «Investments for the future»). We thank Véronique Gire and Philippe Fort (CRBM, CNRS, Montpellier) for helpful discussions. Mass spectrometry experiments were carried out using the facilities of the Montpellier Proteomics Platform (PPM, BioCampus Montpellier). We acknowledge Maurice Wilkins Centre for Molecular Biodiscovery for RNAseq funding. Publisher Copyright: © 2021, The Author(s).

PY - 2021/9/15

Y1 - 2021/9/15

N2 - 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.

AB - 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.

KW - Cancer

KW - Cell Biology

UR - http://www.scopus.com/inward/record.url?scp=85115239726&partnerID=8YFLogxK

U2 - 10.1038/s41467-021-25550-2

DO - 10.1038/s41467-021-25550-2

M3 - Article

C2 - 34526502

AN - SCOPUS:85115239726

SN - 2041-1723

VL - 12

JO - Nature Communications

JF - Nature Communications

M1 - 5463

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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