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The ‘Complex World’ of the Hsp90 Co-chaperone R2TP

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Heat Shock Protein 90 in Human Diseases and Disorders

Part of the book series: Heat Shock Proteins ((HESP,volume 19))

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Abstract

The Hsp90 co-chaperone R2TP consists of the AAA+ ATPases, RUVBL1 (Rvb1p in yeast) and RUVBL2 (Rvb2p in yeast), which together make up a heterohexameric ring, in complex with PIH1D1 (Pih1p in yeast) and RPAP3 (Tah1p in yeast). R2TP is involved in the activation of client proteins, such as phosphatidylinositol 3 kinase-related kinases, including mTORC1, ATM, DNA-PK, SMG and ATR/ATRIP, or in the assembly of protein complexes including those of RNA polymerase and snoRNPs, amongst others. In other cases, the role of the TP component (RPAP3-PIH1D1) of R2TP, and consequently Hsp90, is controversial. None-the-less, the extensive role of RUVBL1-RUVBL2 complex in cells, either with or without Hsp90, means that dysfunction of these AAA+ ATPases, Hsp90 or components of the complexes they assemble leads to diseases such as cancer, ciliary dyskinesia and in the case of defects in ATM to ataxia telangiectasia-like syndrome. Recent advances in determining the structure of the R2TP complex has led to an increased understanding of the assembly and function of the R2TP complex. In this review we discuss the current structural advances in determining the architecture of the R2TP complex and the advances made in understanding its active state.

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Abbreviations

EM:

Electron microscopy

Hsp90:

Heat shock protein 90

R2:

RUVBL1-RUVBL2 complex

R2TP:

RUVBL1 RUVBL2-RPAP3-PIH1D1 or Rvb1p-Rvb2p-Pih1p-Tah1p complex

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Authors and Affiliations

  1. Biochemistry and Biomedicine, University of Sussex, Falmer, Brighton, UK

    Chrisostomos Prodromou

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  1. Chrisostomos Prodromou
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Correspondence to Chrisostomos Prodromou .

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Editors and Affiliations

  1. Department of Medicine and Director, Precision Therapeutics Proteogenomics Diagnostic Center, Eleanor N. Dana Cancer Center, University of Toledo, College of Medicine and Life Sciences, Toledo, OH, USA

    Alexzander A. A. Asea

  2. Department of Experimental Radiation Oncology, MD Anderson Cancer Center, Houston, TX, USA

    Punit Kaur

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Prodromou, C. (2019). The ‘Complex World’ of the Hsp90 Co-chaperone R2TP. In: Asea, A., Kaur, P. (eds) Heat Shock Protein 90 in Human Diseases and Disorders. Heat Shock Proteins, vol 19. Springer, Cham. https://doi.org/10.1007/978-3-030-23158-3_15

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