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An R2TP- 4 and URI1 Prefoldin-Based Chaperone Complex

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The Multiple Functions of the PAQosome: An R2TP- 4 and URI1 Prefoldin-Based Chaperone Complex Jeffrey Lynham and Walid A. Houry Abstract higher metazoans. Although the URI1 pre- The PAQosome (Particle for Arrangement of foldin complex was initially reported more Quaternary structure) is a large multisubunit than 15 years ago, little is known about its chaperone complex that is essential for the function and its role within the PAQosome. assembly and stabilization of other macromo- Given that URI1 is overexpressed in many lecular complexes. It also interacts with sev- types of cancer, it is surprising that the URI1 eral chaperones including Hsp90, Hsp70, and prefoldin complex has been overlooked. This CCT. The PAQosome is comprised of the chapter provides an update on the recent prog- R2TP complex, the URI1 prefoldin complex ress uncovering the physiological roles of (also known as the non-canonical­ prefoldin- each PAQosome subunit and provides an over- like complex), the RNA polymerase subunit view of the potential functions of the URI1 RPB5, and the WD40 repeat protein WDR92. prefoldin complex. The R2TP complex is conserved among eukaryotes and has been comprehensively Keywords studied over the last 13 years. The R2TP com- Molecular chaperones · R2TP · URI1 · plex is known for its involvement in the PAQosome · RNA polymerase assembly · assembly and stabilization of L7Ae ribonu- Non-canonical prefoldin complex · cleoproteins, U5 small nuclear ribonucleopro- Quaternary structure · snoRNP biogenesis · tein, RNA polymerase II, PIKK stabilization · U5 snRNP · TSC phosphatidylinositol-3-kinase-related proteins (PIKKs), and the tuberous sclerosis complex (TSC1-TSC2). By contrast, the URI1 pre- foldin complex has evolved exclusively in 4.1 Overview J. Lynham Molecular chaperones and their co-chaperones Department of Biochemistry, University of Toronto, play key roles in maintaining proteostasis in Toronto, ON, Canada response to environmental and stress conditions W. A. Houry (*) (Hartl et al. 2011). The R2TP chaperone complex Department of Biochemistry, University of Toronto, (see Table 4.1 for nomenclature) was identified in Toronto, ON, Canada a large-scale genomic and proteomic screen for Department of Chemistry, University of Toronto, Hsp90 co-factors in yeast (Zhao et al. 2005b), Toronto, ON, Canada and it was subsequently shown to be conserved in e-mail: [email protected] © Springer Nature Switzerland AG 2018 37 N. Djouder (ed.), Prefoldins: the new chaperones, Advances in Experimental Medicine and Biology 1106, https://doi.org/10.1007/978-3-030-00737-9_4 38 J. Lynham and W. A. Houry Table 4.1 Nomenclature αPFD Alpha prefoldin domain EFTUD2 Elongation factor tu GTP binding αMHC Alpha myosin heavy chain domain containing 2 βPFD Beta prefoldin domain EGFR Epidermal growth factor receptor AAA+ ATPases associated with diverse cellular eIF1A Eukaryotic initiation factor 1A activities ER Estrogen receptor AAR2 A1-Alpha2 repression EVI1 Ecotropic viral integration site 1 AhR Aryl hydrocarbon receptor EZH1 Enhancer of zeste homolog 2 AFMID Arylformamidase FBL Fibrillarin ALS2 Amyotrophic lateral sclerosis 2 protein FOG2 Friend of GATA protein 2 ANP Atrial natriuretic peptide FOXP3 Forkhead box P3 AR Androgen receptor GAR1 Glycine arginine rich protein 1 ART-27 Androgen receptor trapped clone 27 GATA4 GATA binding protein 4 protein Gim1 GimC subunit 1 Asa1 ASTRA-associated protein 1 Gim4 GimC subunit 4 ASTRA Assembly of Tel, Rvb and Atm-like GimC Genes involved in microtubule kinase biogenesis complex ATM Ataxia-telangiectasia mutated Gcn4 General control protein 4 ATR ATM- and RAD3-related HAAO 3-hydroxyanthranilate 3,4-dioxygenase BAD Bcl-2 associated death promoter HBV Hepatitis B virus BAX Bcl-2 associated X protein HBx Hepatitis B virus X protein Bcd1 Box C/D snoRNA accumulation 1 Hit1 High temperature growth 1 Bcl-2 B-cell leukemia/lymphoma 2 HKE2 HLA class II region expressed gene BNP B-type natriuretic peptide KE2 Bud27 Bud site selection protein 27 Hsp70 Heat shock protein 70 CCDC103 Coiled-coil domain containing 103 Hsp90 Heat shock protein 90 CCT Complex containing TCP-1 HLE Human hepatoma cell line CDC73 Cell division cycle protein 73 homolog IL-6 Interleukin-6 CDK1 Cyclin-dependent kinase 1 INO80 Inositol biosynthesis genes 80 CHX Cyclohexamide IP6K2 Inositol Hexakisphosphate kinase 2 CK2 Casein kinase 2 KAP1 KRAB-associated protein 1 CLN3 Cyclin 3 KNYU Kynureninase CREB cAMP responsive element binding KMO Kynurenine 3-monooxygenase protein KRAB Krüppel associated box COP9 Constitutive photomorphogenesis 9 LEO1 RNA polymerase-associate protein left CS CHORD domain-containing protein and open reading frame 1 Sgt1 domain LINE-1 Long interspersed nuclear element 1 CSN2 COP9 signalosome 2 LOX-PP Lysyl oxidase precursor protein CTR9 Cln3 requiring 9 LLRC6 Leucine rich repeat containing 6 DKC1 Dyskerin LRP16 Leukemia-related protein 16 DMAP1 DNA methyltransferase associated MAPKAP1 Mitogen-activated protein kinase protein 1 associated protein 1 DNA-PK DNA-dependent protein kinase Matα1 Methionine adenosyltransferase alpha 1 DNA-PKcs DNA–protein kinase catalytic subunit MAT I Methionine adenosyltransferase I DNAAF1 Dynein axonemal assembly factor 1 MAT III Methionine adenosyltransferase III DNAAF2 Dynein axonemal assembly factor 2 Mec1 Mitosis entry checkpoint 1 DNAAF4 Dynein axonemal assembly factor 4 MEF Mouse embryonic fibroblast DSCR1 Down syndrome critical region gene 1 MDM4 Mouse double minute 4, human ECD Ecdysoneless homolog homolog of; p53 binding protein EFsec Selenocysteine-specific eukaryotic MHC Major histocompatibility elongation factor miR-214 MicroRNA 214 (continued) 4 The Multiple Functions of the PAQosome: An R2TP- and URI1 Prefoldin-Based Chaperone Complex 39 Table 4.1 (continued) MLST8 Mammalian lethal with SEC13 protein PRAS40 Proline-rich Akt substrate 8 PRP8 Pre-mRNA-processing factor 8 MOT48 Motile flagella 48 PRP31 Pre-mRNA-processing factor 31 MRE11 Meiotic recombination 11 RAD50 Radiation sensitive 50 MRN Mre11-Rad50-Nbs1 RSC Remodel of the structure of chromatin mRNP Messenger ribonucleoprotein complex mTOR Mammalian target of rapamycin RSC4 Remodel of the structure of chromatin mTORC1 Mammalian target of rapamycin complex subunit 4 complex 1 RMP RNA polymerase II subunit 5-mediating mTORC2 Mammalian target of rapamycin protein complex 2 RNAP RNA polymerase NAD+ Nicotinamide adenine dinucleotide RNP Ribonucleoprotein NAF1 Nuclear assembly factor 1 R2TP Rvb1–Rvb2–Tah1–Pih1 NBS1 Nibrin Rpa190 DNA directed RNA polymerase I NHP2 Non-histone protein 2 190 kDa polypeptide NKX2.5 NK2 Homeobox 5 RPAP3 RNA polymerase II-associated protein 3 NF-κB Nuclear factor kappa beta RPB1 RNA polymerase II subunit B1 NOP1 Nucleolar protein 1 RPB5 RNA polymerase II subunit B5 NOP10 Nucleolar protein 10 Rpc25 DNA-directed RNA polymerase III NOP56 Nucleolar protein 56 25 kDa polypeptide NOP58 Nucleolar protein 58 RPN8 Regulatory particle non-ATPase 8 NUFIP1 Nuclear FMRP interacting protein 1 Rsa1 Ribosome assembly protein 1 OCT1 Organic cation transporter 1 RuvBL1 RuvB-like AAA ATPase 1 OGT O-linked N-acetylglucosamine RuvBL2 RuvB-like AAA ATPase 2 transferase 110 kDa subunit S6K1 Ribosomal protein S6 kinase beta-1 OIP2 Opa-interacting protein 2 SARM Selective androgen receptor modulator PAF1 RNA polymerase II-associated factor 1 SBP2 SECIS binding protein 2 PAQosome Particle for arrangement of quaternary SECIS Selenocysteine insertion sequence structure SHQ1 Small nucleolar RNAs of the box H/ PEP Phosphoenolpyruvate ACA family quantitative accumulation PDRG1 p53 and DNA damage regulated 1 1 PFDN1 Prefoldin subunit 1 SNCG Gamma synuclein PFDN2 Prefoldin subunit 2 SKP2 S-phase kinase-associated protein 2 PFDN3 Prefoldin subunit 3 SMN Survival motor neuron PFDN4 Prefoldin subunit 4 SMG-1 Nonsense-mediated mRNA decay associated phosphatidylinositol-3-­ PFDN4r Prefoldin subunit 4-related kinase-related kinase PFDN5 Prefoldin subunit 5 SNF5 Sucrose non-fermentable 5 PFDN6 Prefoldin subunit 6 snoRNA Small nucleolar RNA PIAS2 Protein inhibitor of activated STAT2 snoRNP Small nucleolar ribonucleoprotein PIH1 PIH1 homology domain snRNP Small nuclear ribonucleoprotein Pih1 Protein interacting with Hsp90 SNRNP200 Small nuclear ribonucleoprotein U5 PIH1D1 PIH1 domain-containing protein 1 subunit 200 PIH1D3 PIH1 domain-containing protein 3 SNU13 Small nuclear ribonucleoprotein 13 PIKK Phosphatidylinositol-3-kinase-related SPAG1 Sperm-associated antigen 1 kinase Spt5 Suppressor of ty 5 PKA Protein kinase A STAP1 SKP2-associated alpha prefoldin 1 POLR2E RNA polymerase II subunit E STAT2 Signal transducer and activator of POLR2M RNA polymerase II subunit M transcription 2 PP1γ Protein phosphatase 1 catalytic subunit Sth5 SNF two homolog gamma SUZ12 Suppressor of zeste 12 protein homolog PP2A Protein phosphatase 2A (continued) 40 J. Lynham and W. A. Houry Table 4.1 (continued) ious macromolecular complexes including L7Ae SWI Switching deficient RNPs (Boulon et al. 2008; Machado-Pinilla et al. SWR1 SWI/SNF related protein 2012; Zhao et al. 2008), U5 snRNP (Cloutier Tah1 TPR-containing protein associated with et al. 2017; Malinova et al. 2017), RNAP II Hsp90 (Boulon et al. 2010), PIKK complexes (Horejsi TBC1D7 Tre2-Bub2-Cdc16 domain family member 7 et al. 2010), the MRN complex (von Morgen TERC Telomerase RNA component et al. 2017), and the TSC complex (Cloutier et al. TERT Telomerase reverse transcriptase 2017; Malinova et al. 2017). In addition, R2TP-­ TDO2 Tryptophan 2,3-dioxygenase like complexes have been hypothesized to medi-
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  • 1 Introduction + 1.1 Ruvbl1 and Ruvbl2 Are Highly Conserved AAA Proteins

    1 Introduction + 1.1 Ruvbl1 and Ruvbl2 Are Highly Conserved AAA Proteins

    1. Introduction 1 Introduction + 1.1 RuvBL1 and RuvBL2 are highly conserved AAA proteins RuvBL1 and its homolog RuvBL2 are ubiquitously expressed proteins (Bauer et al. 1998) that belong to the AAA+ family of ATPases (ATPases associated with diverse cellular activities) (Neuwald et al. 1999). This class of ATPases includes nucleic acid processing enzymes, chaperones and proteases. AAA+ proteins often form hexameric ring structures and contain conserved motifs for ATP binding and hydrolysis like the Walker A (GXXXXGKT) and Walker B box (DEXH/N) (Walker et al. 1982), the Arg-finger and sensor residues. All AAA+ proteins use ATP binding and hydrolysis to exert mechanical forces. ATP hydrolysis is clearly essential for the biological activity of RuvBL1 and RuvBL2 (Feng et al. 2003; Jonsson et al. 2004; Wood et al. 2000). RuvBL1 and RuvBL2, consisting of 456 and 463 amino acids respectively, are mainly localised in the nucleus, but also found in the cytosol (Holzmann et al. 1998; Kim et al. 2006; Lim et al. 2000; Salzer et al. 1999). RuvBL2 exhibits 43 % sequence identity and 65 % sequence similarity to RuvBL1. These proteins were originally identified by several unrelated approaches and are therefore known under diverse names (see Table 1). RuvBL1 RuvBL2 Explanation Reference TIP49 TIP48 TATA-binding protein (TBP)-interacting protein (Makino et al. 1998; Wood et al. 2000) TIP49a TIP49b TBP-interacting protein (Kanemaki et al. 1999) Pontin52 Reptin52 repressing Pontin52 (Bauer et al. 2000; Bauer et al. 1998) TAP54α TAP54β TIP60-associated protein (Ikura et al. 2000) TIH1 TIH2 TIP49a/b homolog (Lim et al. 2000) ECP54 ECP51 erythrocyte cytosolic protein (Salzer et al.