The HSP90/R2TP Quaternary Chaperone Scaffolds Assembly of the TSC Complex.

Autor: Abéza C; IGMM, CNRS, Univ Montpellier, Montpellier, France; Equipe labellisée Ligue Nationale Contre le Cancer, Montpellier, France; IGH, CNRS, Univ Montpellier, Montpellier, France., Busse P; iBET, Instituto de Biologia Experimental e Tecnologica, Apartado 12, Oeiras, 2781-901, Portugal; Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Av. da República, 2780-157 Oeiras, Portugal., Paiva ACF; iBET, Instituto de Biologia Experimental e Tecnologica, Apartado 12, Oeiras, 2781-901, Portugal; Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Av. da República, 2780-157 Oeiras, Portugal., Chagot ME; Université de Lorraine, CNRS, IMoPA, F-54000 Nancy, France., Schneider J; LSMBO, IPHC, Université de Strasbourg, CNRS UMR7178, Strasbourg, France., Robert MC; IGMM, CNRS, Univ Montpellier, Montpellier, France; Equipe labellisée Ligue Nationale Contre le Cancer, Montpellier, France; IGH, CNRS, Univ Montpellier, Montpellier, France., Vandermoere F; IGF, CNRS, INSERM, Univ Montpellier, Montpellier, France., Schaeffer C; LSMBO, IPHC, Université de Strasbourg, CNRS UMR7178, Strasbourg, France., Charpentier B; Université de Lorraine, CNRS, IMoPA, F-54000 Nancy, France., Sousa PMF; iBET, Instituto de Biologia Experimental e Tecnologica, Apartado 12, Oeiras, 2781-901, Portugal., Bandeiras TM; iBET, Instituto de Biologia Experimental e Tecnologica, Apartado 12, Oeiras, 2781-901, Portugal., Manival X; Université de Lorraine, CNRS, IMoPA, F-54000 Nancy, France., Cianferani S; LSMBO, IPHC, Université de Strasbourg, CNRS UMR7178, Strasbourg, France., Bertrand E; IGMM, CNRS, Univ Montpellier, Montpellier, France; Equipe labellisée Ligue Nationale Contre le Cancer, Montpellier, France; IGH, CNRS, Univ Montpellier, Montpellier, France. Electronic address: edouard.bertrand@igh.cnrs.fr., Verheggen C; IGMM, CNRS, Univ Montpellier, Montpellier, France; Equipe labellisée Ligue Nationale Contre le Cancer, Montpellier, France; IGH, CNRS, Univ Montpellier, Montpellier, France. Electronic address: celine.verheggen@igh.cnrs.fr.
Jazyk: angličtina
Zdroj: Journal of molecular biology [J Mol Biol] 2024 Oct 26; Vol. 436 (23), pp. 168840. Date of Electronic Publication: 2024 Oct 26.
DOI: 10.1016/j.jmb.2024.168840
Abstrakt: The R2TP chaperone is composed of the RUVBL1/RUVBL2 AAA+ ATPases and two adapter proteins, RPAP3 and PIH1D1. Together with HSP90, it functions in the assembly of macromolecular complexes that are often involved in cell proliferation. Here, proteomic experiments using the isolated PIH domain reveals additional R2TP partners, including the Tuberous Sclerosis Complex (TSC) and many transcriptional complexes. The TSC is a key regulator of mTORC1 and is composed of TSC1, TSC2 and TBC1D7. We show a direct interaction of TSC1 with the PIH phospho-binding domain of PIH1D1, which is, surprisingly, phosphorylation independent. Via the use of mutants and KO cell lines, we observe that TSC2 makes independent interactions with HSP90 and the TPR domains of RPAP3. Moreover, inactivation of PIH1D1 or the RUVBL1/2 ATPase activity inhibits the association of TSC1 with TSC2. Taken together, these data suggest a model in which the R2TP recruits TSC1 via PIH1D1 and TSC2 via RPAP3 and HSP90, and use the chaperone-like activities of RUVBL1/2 to stimulate their assembly.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
Databáze: MEDLINE
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