title: Substrate recognition and function of the R2TP complex in response to cellular stress.
abstract: The R2TP complex is a HSP90 co-chaperone, which consists of four subunits: PIH1D1, RPAP3, RUVBL1, and RUVBL2. It is involved in the assembly of large protein or protein-RNA complexes such as RNA polymerase, small nucleolar ribonucleoproteins (snoRNPs), phosphatidylinositol 3 kinase-related kinases (PIKKs), and their complexes. While RPAP3 has a HSP90 binding domain and the RUVBLs comprise ATPase activities important for R2TP functions, PIH1D1 contains a PIH-N domain that specifically recognizes phosphorylated substrates of the R2TP complex. In this review we provide an overview of the current knowledge of the R2TP complex with the focus on the recently identified structural and mechanistic features of the R2TP complex functions. We also discuss the way R2TP regulates cellular response to stress caused by low levels of nutrients or by DNA damage and its possible exploitation as a target for anti-cancer therapy.
authors.affiliation: Department of Cancer Cell Biology, Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Prague Czech Republic.
authors.forename: Patrick
authors.initials: P
authors.lastname: von Morgen
authors.affiliation: Department of Cancer Cell Biology, Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Prague Czech Republic ; DNA Damage Response Laboratory, London Research Institute, London UK.
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Hořejší
authors.affiliation: Department of Cancer Cell Biology, Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Prague Czech Republic.
authors.forename: Libor
authors.initials: L
authors.lastname: Macurek
keywords: DNA damage response; R2TP complex; cancer; cellular stress; protein folding