Substrate recognition and function of the R2TP complex in response to cellular stress

Frontiers in Genetics
Patrick von MorgenLibor Macurek

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.

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Citations

Oct 8, 2016·RNA Biology·Séverine MassenetCéline Verheggen
Jul 23, 2015·PloS One·Christian GentiliStefano Ferrari
Nov 9, 2017·MBio·Nir DraymanUri Alon
Jun 20, 2018·ELife·Girish R MaliPleasantine Mill
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May 11, 2018·The Journal of Cell Biology·Petra Zur LageAndrew P Jarman
Sep 9, 2017·Frontiers in Molecular Biosciences·Yu-Qian Mao, Walid A Houry
Nov 19, 2019·Journal of Proteome Research·Philippe CloutierBenoit Coulombe

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Methods Mentioned

BETA
protein folding
electron
scanning
transmission electron microscopy
pull-down
acetylation
xenograft

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