title: HSP90 and the R2TP co-chaperone complex: building multi-protein machineries essential for cell growth and gene expression.
abstract: HSP90 (Heat Shock Protein 90) is an essential chaperone involved in the last folding steps of client proteins. It has many clients, and these are often recognized through specific adaptors. Recently, the conserved R2TP complex was identified as a key HSP90 co-chaperone. Current evidences indicate that the HSP90/R2TP system assembles multi-molecular protein complexes. Strikingly, these comprise basic machineries of gene expression: (1) nuclear RNA polymerases; (2) the snoRNPs, essential to produce ribosomes; and (3) mTOR Complex 1 and 2, which control translational activity and cell growth. Another important substrate is the telomerase RNP, required for continuous cell proliferation. We discuss here the assembly of RNA polymerases in bacteria and eukaryotes, the role of HSP90/R2TP in this process and in the assembly of snoRNPs and the PIKK family of TORC1 kinase. Finally, we speculate on the roles of R2TP as a master regulator of cell growth under normal or pathological conditions.
authors.affiliation: Centre de Recherche de Biochimie Macromoléculaire, CNRS, Université Montpellier; Montpellier, France.
authors.forename: Séverine
authors.initials: S
authors.lastname: Boulon
authors.forename: Edouard
authors.initials: E
authors.lastname: Bertrand
authors.forename: Bérengère
authors.initials: B
authors.lastname: Pradet-Balade
mesh_terms: D049109:Cell Proliferation; D005786:Gene Expression Regulation; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism*; D008954:Models, Biological; D018832:Molecular Chaperones / Q000378:metabolism; D046912:Multiprotein Complexes / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism*; D011485:Protein Binding; D012319:RNA Polymerase II / Q000378:metabolism; D020718:Ribonucleoproteins, Small Nucleolar / Q000378:metabolism
chemical_list: D018841:HSP90 Heat-Shock Proteins; D018832:Molecular Chaperones; D046912:Multiprotein Complexes; D009687:Nuclear Proteins; D020718:Ribonucleoproteins, Small Nucleolar; D012319:RNA Polymerase II