Fiche publication
Date publication
octobre 2024
Journal
Journal of molecular biology
Auteurs
Membres identifiés du Cancéropôle Est :
Pr CHARPENTIER Bruno
,
Dr CIANFERANI Sarah
,
Dr MANIVAL Xavier
Tous les auteurs :
Abéza C, Busse P, Paiva ACF, Chagot ME, Schneider J, Robert MC, Vandermoere F, Schaeffer C, Charpentier B, M F Sousa P, Bandeiras TM, Manival X, Cianferani S, Bertrand E, Verheggen C
Lien Pubmed
Résumé
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.
Mots clés
2), ATPases associated with diverse cellular activities (RUVBL1, R2TP, Tuberous sclerosis complex (TSC), heat shock protein 90 (HSP90), protein‐protein interaction
Référence
J Mol Biol. 2024 10 26;:168840
