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

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 (...

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Autores principales: von Morgen, Patrick, Hořejší, Zuzana, Macurek, Libor
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4341119/
https://www.ncbi.nlm.nih.gov/pubmed/25767478
http://dx.doi.org/10.3389/fgene.2015.00069
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author von Morgen, Patrick
Hořejší, Zuzana
Macurek, Libor
author_facet von Morgen, Patrick
Hořejší, Zuzana
Macurek, Libor
author_sort von Morgen, Patrick
collection PubMed
description 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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spelling pubmed-43411192015-03-12 Substrate recognition and function of the R2TP complex in response to cellular stress von Morgen, Patrick Hořejší, Zuzana Macurek, Libor Front Genet Genetics 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. Frontiers Media S.A. 2015-02-25 /pmc/articles/PMC4341119/ /pubmed/25767478 http://dx.doi.org/10.3389/fgene.2015.00069 Text en Copyright © 2015 von Morgen, Hořejší and Macurek. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Genetics
von Morgen, Patrick
Hořejší, Zuzana
Macurek, Libor
Substrate recognition and function of the R2TP complex in response to cellular stress
title Substrate recognition and function of the R2TP complex in response to cellular stress
title_full Substrate recognition and function of the R2TP complex in response to cellular stress
title_fullStr Substrate recognition and function of the R2TP complex in response to cellular stress
title_full_unstemmed Substrate recognition and function of the R2TP complex in response to cellular stress
title_short Substrate recognition and function of the R2TP complex in response to cellular stress
title_sort substrate recognition and function of the r2tp complex in response to cellular stress
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4341119/
https://www.ncbi.nlm.nih.gov/pubmed/25767478
http://dx.doi.org/10.3389/fgene.2015.00069
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