The prefoldin complex stabilizes the von Hippel-Lindau protein against aggregation and degradation
Autoři:
Franck Chesnel aff001; Anne Couturier aff001; Adrien Alusse aff001; Jean-Philippe Gagné aff002; Guy G. Poirier aff002; Dominique Jean aff004; François-Michel Boisvert aff004; Pauline Hascoet aff001; Luc Paillard aff001; Yannick Arlot-Bonnemains aff001; Xavier Le Goff aff001
Působiště autorů:
Univ Rennes, CNRS, IGDR (Institut de génétique et développement de Rennes)—UMR 6290, France
aff001; Department of Molecular Biology, Medical Biochemistry and Pathology; Université Laval, Québec City, Québec, Canada
aff002; CHU de Québec Research Center, CHUL Pavilion, Oncology Axis, Québec City, Québec, Canada
aff003; Department of Anatomy and Cell Biology, Université de Sherbrooke, Sherbrooke, Québec, Canada
aff004
Vyšlo v časopise:
The prefoldin complex stabilizes the von Hippel-Lindau protein against aggregation and degradation. PLoS Genet 16(11): e32767. doi:10.1371/journal.pgen.1009183
Kategorie:
Research Article
doi:
https://doi.org/10.1371/journal.pgen.1009183
Souhrn
Loss of von Hippel-Lindau protein pVHL function promotes VHL diseases, including sporadic and inherited clear cell Renal Cell Carcinoma (ccRCC). Mechanisms controlling pVHL function and regulation, including folding and stability, remain elusive. Here, we have identified the conserved cochaperone prefoldin complex in a screen for pVHL interactors. The prefoldin complex delivers non-native proteins to the chaperonin T-complex-protein-1-ring (TRiC) or Cytosolic Chaperonin containing TCP-1 (CCT) to assist folding of newly synthesized polypeptides. The pVHL-prefoldin interaction was confirmed in human cells and prefoldin knock-down reduced pVHL expression levels. Furthermore, when pVHL was expressed in Schizosaccharomyces pombe, all prefoldin mutants promoted its aggregation. We mapped the interaction of prefoldin with pVHL at the exon2-exon3 junction encoded region. Low levels of the PFDN3 prefoldin subunit were associated with poor survival in ccRCC patients harboring VHL mutations. Our results link the prefoldin complex with pVHL folding and this may impact VHL diseases progression.
Klíčová slova:
Fluorescence imaging – HeLa cells – Phenotypes – Protein extraction – Protein folding – Schizosaccharomyces pombe – Small interfering RNA – Yeast
Zdroje
1. Gossage L, Eisen T, Maher ER. VHL, the story of a tumour suppressor gene. Nat Rev Cancer. 2015;15:55–64. doi: 10.1038/nrc3844 25533676
2. Latif F, Tory K, Gnarra J, Yao M, Duh FM, Orcutt ML, et al. Identification of the von Hippel-Lindau disease tumor suppressor gene. Science. 1993;260:1317–1320. doi: 10.1126/science.8493574 8493574
3. Gnarra JR, Tory K, Weng Y, Schmidt L, Wei MH, Li H, et al. Mutations of the VHL tumour suppressor gene in renal carcinoma. Nat Genet. 1994;7: 85–90. doi: 10.1038/ng0594-85 7915601
4. Hascoet P, Chesnel F, Jouan F, Le Goff C, Couturier A, Darrigrand E, et al. The pVHL172 isoform is not a tumor suppressor and up-regulates a subset of pro-tumorigenic genes including TGFB1 and MMP13. Oncotarget. 2017;8:75989–76002. doi: 10.18632/oncotarget.18376 29100286
5. Iliopoulos O, Kibel A, Gray S, Kaelin WG. Tumour suppression by the human von Hippel-Lindau gene product. Nat Med. 1995;1:822–826. doi: 10.1038/nm0895-822 7585187
6. Schoenfeld A, Davidowitz EJ, Burk RD. A second major native von Hippel-Lindau gene product, initiated from an internal translation start site, functions as a tumor suppressor. Proc Natl Acad Sci USA. 1998;95:8817–8822. doi: 10.1073/pnas.95.15.8817 9671762
7. Iwai K, Yamanaka K, Kamura T, Minato N, Conaway RC, Conaway JW, et al. Identification of the von Hippel-lindau tumor-suppressor protein as part of an active E3 ubiquitin ligase complex. Proc Natl Acad Sci USA. 1999;96:12436–12441. doi: 10.1073/pnas.96.22.12436 10535940
8. Lisztwan J, Imbert G, Wirbelauer C, Gstaiger M, Krek W. The von Hippel-Lindau tumor suppressor protein is a component of an E3 ubiquitin-protein ligase activity. Genes Dev. 1999;13:1822–1833. doi: 10.1101/gad.13.14.1822 10421634
9. Li M, Kim WY. Two sides to every story: the HIF-dependent and HIF-independent functions of pVHL. J Cell Mol Med. 2011;15:187–195. doi: 10.1111/j.1582-4934.2010.01238.x 21155973
10. Rechsteiner MP, von Teichman A, Nowicka A, Sulser T, Schraml P, Moch H. VHL gene mutations and their effects on hypoxia inducible factor HIFα: identification of potential driver and passenger mutations. Cancer Res. 2011;71:5500–5511. doi: 10.1158/0008-5472.CAN-11-0757 21715564
11. Ding Z, German P, Bai S, Reddy AS, Liu X-D, Sun M, et al. Genetic and Pharmacological Strategies to Refunctionalize the von Hippel Lindau R167Q Mutant Protein. Cancer Res. 2014;74:3127–3136. doi: 10.1158/0008-5472.CAN-13-3213 24755468
12. Yang C, Huntoon K, Ksendzovsky A, Zhuang Z, Lonser RR. Proteostasis modulators prolong missense VHL protein activity and halt tumor progression. Cell Rep. 2013;3:52–59. doi: 10.1016/j.celrep.2012.12.007 23318261
13. Sahlan M, Zako T, Yohda M. Prefoldin, a jellyfish-like molecular chaperone: functional cooperation with a group II chaperonin and beyond. Biophys Rev. 2018;10:339–345. doi: 10.1007/s12551-018-0400-0 29427249
14. Arranz R, Martín-Benito J, Valpuesta JM. Structure and Function of the Cochaperone Prefoldin. Adv Exp Med Biol. 2018;1106:119–131. doi: 10.1007/978-3-030-00737-9_9 30484157
15. Frydman J, Nimmesgern E, Erdjument-Bromage H, Wall JS, Tempst P, Hartl FU. Function in protein folding of TRiC, a cytosolic ring complex containing TCP-1 and structurally related subunits. EMBO J. 1992;11:4767–4778. 1361170
16. Geissler S, Siegers K, Schiebel E. A novel protein complex promoting formation of functional alpha- and gamma-tubulin. EMBO J. 1998;17:952–966. doi: 10.1093/emboj/17.4.952 9463374
17. Gestaut D, Roh SH, Ma B, Pintilie G, Joachimiak LA, Leitner A, et al. The Chaperonin TRiC/CCT Associates with Prefoldin through a Conserved Electrostatic Interface Essential for Cellular Proteostasis. Cell. 2019;177:751–765.e15. doi: 10.1016/j.cell.2019.03.012 30955883
18. Martín-Benito J, Boskovic J, Gómez-Puertas P, Carrascosa JL, Simons CT, Lewis SA, et al. Structure of eukaryotic prefoldin and of its complexes with unfolded actin and the cytosolic chaperonin CCT. EMBO J. 2002;21:6377–6386. doi: 10.1093/emboj/cdf640 12456645
19. Siegert R, Leroux MR, Scheufler C, Hartl FU, Moarefi I. Structure of the molecular chaperone prefoldin: unique interaction of multiple coiled coil tentacles with unfolded proteins. Cell. 2000;103:621–632. doi: 10.1016/s0092-8674(00)00165-3 11106732
20. Vainberg IE, Lewis SA, Rommelaere H, Ampe C, Vandekerckhove J, Klein HL, et al. Prefoldin, a chaperone that delivers unfolded proteins to cytosolic chaperonin. Cell. 1998;93:863–873. doi: 10.1016/s0092-8674(00)81446-4 9630229
21. Hansen WJ, Cowan NJ, Welch WJ. Prefoldin-nascent chain complexes in the folding of cytoskeletal proteins. J Cell Biol. 1999;145:265–277. doi: 10.1083/jcb.145.2.265 10209023
22. Lacefield S, Solomon F. A novel step in beta-tubulin folding is important for heterodimer formation in Saccharomyces cerevisiae. Genetics. 2003;165:531–541. 14573467
23. Lacefield S, Magendantz M, Solomon F. Consequences of defective tubulin folding on heterodimer levels, mitosis and spindle morphology in Saccharomyces cerevisiae. Genetics. 2006;173:635–646. doi: 10.1534/genetics.105.055160 16582437
24. Rommelaere H, De Neve M, Neirynck K, Peelaers D, Waterschoot D, Goethals M, et al. Prefoldin recognition motifs in the nonhomologous proteins of the actin and tubulin families. J Biol Chem. 2001;276:41023–41028. doi: 10.1074/jbc.M106591200 11535601
25. Henkel J, Du H, Yang P, Qyang Y, Kansra S, Ko M, et al. Bob1, a Gim5/MM-1/Pfd5 homolog, interacts with the MAP kinase kinase Byr1 to regulate sexual differentiation in the fission yeast, Schizosaccharomyces pombe. Differentiation. 2001;67:98–106. doi: 10.1046/j.1432-0436.2001.670402.x 11683500
26. Le Goff X, Chesnel F, Delalande O, Couturier A, Dréano S, Le Goff C, et al. Aggregation dynamics and identification of aggregation-prone mutants of the von Hippel-Lindau tumor suppressor protein. J Cell Sci. 2016;129:2638–2650. doi: 10.1242/jcs.184846 27179072
27. Satou A, Taira T, Iguchi-Ariga SM, Ariga H. A novel transrepression pathway of c-Myc. Recruitment of a transcriptional corepressor complex to c-Myc by MM-1, a c-Myc-binding protein. J Biol Chem. 2001;276:46562–46567. doi: 10.1074/jbc.M104937200 11585818
28. Wang D, Shi W, Tang Y, Liu Y, He K, Hu Y, et al. Prefoldin 1 promotes EMT and lung cancer progression by suppressing cyclin A expression. Oncogene. 2017;36:885–898. doi: 10.1038/onc.2016.257 27694898
29. Tsuchiya H, Iseda T, Hino O. Identification of a novel protein (VBP-1) binding to the von Hippel-Lindau (VHL) tumor suppressor gene product. Cancer Res. 1996;56:2881–2885. 8674032
30. Kim JA, Choi DK, Min JS, Kang I, Kim JC, Kim S, et al. VBP1 represses cancer metastasis by enhancing HIF-1α degradation induced by pVHL. FEBS J. 2018;285:115–126. doi: 10.1111/febs.14322 29121446
31. Delgehyr N, Wieland U, Rangone H, Pinson X, Mao G, Dzhindzhev NS, et al. Drosophila Mgr, a Prefoldin subunit cooperating with von Hippel Lindau to regulate tubulin stability. Proc Natl Acad Sci USA. 2012;109:5729–5734. doi: 10.1073/pnas.1108537109 22451918
32. Feldman DE, Spiess C, Howard DE, Frydman J. Tumorigenic mutations in VHL disrupt folding in vivo by interfering with chaperonin binding. Mol Cell. 2003;12:1213–1224. doi: 10.1016/s1097-2765(03)00423-4 14636579
33. Umesono K, Toda T, Hayashi S, Yanagida M. Cell division cycle genes nda2 and nda3 of the fission yeast Schizosaccharomyces pombe control microtubular organization and sensitivity to anti-mitotic benzimidazole compounds. J Mol Biol. 1983;168:271–284. doi: 10.1016/s0022-2836(83)80018-7 6887245
34. Tran PT, Marsh L, Doye V, Inoué S, Chang F. A mechanism for nuclear positioning in fission yeast based on microtubule pushing. J Cell Biol. 2001;153:397–411. doi: 10.1083/jcb.153.2.397 11309419
35. Schoenfeld AR, Davidowitz EJ, Burk RD. Elongin BC complex prevents degradation of von Hippel-Lindau tumor suppressor gene products. Proc Natl Acad Sci USA. 2000;97:8507–8512. doi: 10.1073/pnas.97.15.8507 10900011
36. Theodoraki MA, Nillegoda NB, Saini J, Caplan AJ. A network of ubiquitin ligases is important for the dynamics of misfolded protein aggregates in yeast. J Biol Chem. 2012;287:23911–23922. doi: 10.1074/jbc.M112.341164 22593585
37. McClellan AJ, Scott MD, Frydman J. Folding and quality control of the VHL tumor suppressor proceed through distinct chaperone pathways. Cell. 2005;121:739–748. doi: 10.1016/j.cell.2005.03.024 15935760
38. Sénéchal P, Arseneault G, Leroux A, Lindquist S, Rokeach LA. The Schizosaccharomyces pombe Hsp104 disaggregase is unable to propagate the [PSI] prion. PLoS ONE. 2009;4:e6939. doi: 10.1371/journal.pone.0006939 19759825
39. Vjestica A, Zhang D, Liu J, Oliferenko S. Hsp70-Hsp40 chaperone complex functions in controlling polarized growth by repressing Hsf1-driven heat stress-associated transcription. PLoS Genet. 2013;9:e1003886. doi: 10.1371/journal.pgen.1003886 24146635
40. Nomura M, Nakamori S, Takagi H. Characterization of novel acetyltransferases found in budding and fission yeasts that detoxify a proline analogue, azetidine-2-carboxylic acid. J Biochem. 2003;133:67–74. doi: 10.1093/jb/mvg003 12761200
41. Trotter EW, Berenfeld L, Krause SA, Petsko GA, Gray JV. Protein misfolding and temperature up-shift cause G1 arrest via a common mechanism dependent on heat shock factor in Saccharomycescerevisiae. Proc Natl Acad Sci USA. 2001;98:7313–7318. doi: 10.1073/pnas.121172998 11416208
42. Sawin KE, Snaith HA. Role of microtubules and tea1p in establishment and maintenance of fission yeast cell polarity. J Cell Sci. 2004;117:689–700. doi: 10.1242/jcs.00925 14734657
43. Browning H, Hayles J, Mata J, Aveline L, Nurse P, McIntosh JR. Tea2p is a kinesin-like protein required to generate polarized growth in fission yeast. J Cell Biol. 2000;151:15–28. doi: 10.1083/jcb.151.1.15 11018050
44. Simons CT, Staes A, Rommelaere H, Ampe C, Lewis SA, Cowan NJ. Selective contribution of eukaryotic prefoldin subunits to actin and tubulin binding. J Biol Chem. 2004;279:4196–4203. doi: 10.1074/jbc.M306053200 14634002
45. Abe A, Takahashi-Niki K, Takekoshi Y, Shimizu T, Kitaura H, Maita H, et al. Prefoldin plays a role as a clearance factor in preventing proteasome inhibitor-induced protein aggregation. J Biol Chem. 2013;288:27764–27776. doi: 10.1074/jbc.M113.476358 23946485
46. Miyazawa M, Tashiro E, Kitaura H, Maita H, Suto H, Iguchi-Ariga SMM, et al. Prefoldin subunits are protected from ubiquitin-proteasome system-mediated degradation by forming complex with other constituent subunits. J Biol Chem. 2011;286:19191–19203. doi: 10.1074/jbc.M110.216259 21478150
47. Feldman DE, Thulasiraman V, Ferreyra RG, Frydman J. Formation of the VHL-elongin BC tumor suppressor complex is mediated by the chaperonin TRiC. Mol Cell. 1999;4:1051–1061. doi: 10.1016/s1097-2765(00)80233-6 10635329
48. Minervini G, Quaglia F, Tabaro F, Tosatto SCE. Genotype-phenotype relations of the von Hippel-Lindau tumor suppressor inferred from a large-scale analysis of disease mutations and interactors. PLoS Comput Biol. 2019;15:e1006478. doi: 10.1371/journal.pcbi.1006478 30943211
49. Nordstrom-O’Brien M, van der Luijt RB, van Rooijen E, van den Ouweland AM, Majoor-Krakauer DF, Lolkema MP, et al. Genetic analysis of von Hippel-Lindau disease. Hum Mutat. 2010;31:521–537. doi: 10.1002/humu.21219 20151405
50. Melville MW, McClellan AJ, Meyer AS, Darveau A, Frydman J. The Hsp70 and TRiC/CCT chaperone systems cooperate in vivo to assemble the von Hippel-Lindau tumor suppressor complex. Mol Cell Biol. 2003;23:3141–3151. doi: 10.1128/mcb.23.9.3141-3151.2003 12697815
51. Comyn SA, Young BP, Loewen CJ, Mayor T. Prefoldin Promotes Proteasomal Degradation of Cytosolic Proteins with Missense Mutations by Maintaining Substrate Solubility. PLoS Genet. 2016;12:e1006184. doi: 10.1371/journal.pgen.1006184 27448207
52. Simons CT, Staes A, Rommelaere H, Ampe C, Lewis SA, Cowan NJ. Selective contribution of eukaryotic prefoldin subunits to actin and tubulin binding. J Biol Chem. 2004;279:4196–4203. doi: 10.1074/jbc.M306053200 14634002
53. Siegers K, Schiebel E. Purification of GimC from Saccharomyces cerevisiae. Methods Mol Biol. 2000;140:185–193. doi: 10.1385/1-59259-061-6:185 11484488
54. Gu Y, Deng Z, Paredez AR, DeBolt S, Wang Z- Y, Somerville C. Prefoldin 6 is required for normal microtubule dynamics and organization in Arabidopsis. Proc Natl Acad Sci USA. 2008;105:18064–18069. doi: 10.1073/pnas.0808652105 19004800
55. Lundin VF, Srayko M, Hyman AA, Leroux MR. Efficient chaperone-mediated tubulin biogenesis is essential for cell division and cell migration in C. elegans. Dev Biol. 2008;313:320–334. doi: 10.1016/j.ydbio.2007.10.022 18062952
56. Grantham J, Brackley KI, Willison KR. Substantial CCT activity is required for cell cycle progression and cytoskeletal organization in mammalian cells. Exp Cell Res. 2006;312:2309–2324. doi: 10.1016/j.yexcr.2006.03.028 16765944
57. Kampinga HH, Craig EA. The HSP70 chaperone machinery: J proteins as drivers of functional specificity. Nat Rev Mol Cell Biol. 2010;11:579–592. doi: 10.1038/nrm2941 20651708
58. Samant RS, Livingston CM, Sontag EM, Frydman J. Distinct proteostasis circuits cooperate in nuclear and cytoplasmic protein quality control. Nature. 2018;563:407–411. doi: 10.1038/s41586-018-0678-x 30429547
59. Banks CAS, Miah S, Adams MK, Eubanks CG, Thornton JL, Florens L, et al. Differential HDAC1/2 network analysis reveals a role for prefoldin/CCT in HDAC1/2 complex assembly. Sci Rep. 2018;8:13712. doi: 10.1038/s41598-018-32009-w 30209338
60. Moreno S, Klar A, Nurse P. Molecular genetic analysis of fission yeast Schizosaccharomyces pombe. Meth Enzymol. 1991;194:795–823. doi: 10.1016/0076-6879(91)94059-l
61. Bellemare DR, Sanschagrin M, Beaudoin J, Labbé S. A novel copper-regulated promoter system for expression of heterologous proteins in Schizosaccharomyces pombe. Gene. 2001;273:191–198. doi: 10.1016/s0378-1119(01)00591-1 11595165
62. Bähler J, Wu JQ, Longtine MS, Shah NG, McKenzie A, Steever AB, et al. Heterologous modules for efficient and versatile PCR-based gene targeting in Schizosaccharomyces pombe. Yeast. 1998;14:943–951. doi: 10.1002/(SICI)1097-0061(199807)14:10<943::AID-YEA292>3.0.CO;2-Y 9717240
63. Tan S. A modular polycistronic expression system for overexpressing protein complexes in Escherichia coli. Protein Expr Purif. 2001;21:224–234. doi: 10.1006/prep.2000.1363 11162410
64. Brock KP, Abraham A, Amen T, Kaganovich D, England JL. Structural Basis for Modulation of Quality Control Fate in a Marginally Stable Protein. Structure. 2015;23:1169–1178. doi: 10.1016/j.str.2015.04.015 26027734
65. Hjerpe R, Aillet F, Lopitz-Otsoa F, Lang V, England P, Rodriguez MS. Efficient protection and isolation of ubiquitylated proteins using tandem ubiquitin-binding entities. EMBO Rep. 2009;10:1250–1258. doi: 10.1038/embor.2009.192 19798103
66. Huang DW, Sherman BT, Lempicki RA. Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists. Nucleic Acids Res. 2009;37:1–13. doi: 10.1093/nar/gkn923 19033363
67. Huang DW, Sherman BT, Lempicki RA. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc. 2009;4:44–57. doi: 10.1038/nprot.2008.211 19131956
68. Chesnel F, Hascoet P, Gagné JP, Couturier A, Jouan F, Poirier GG, et al. The von Hippel-Lindau tumour suppressor gene: uncovering the expression of the pVHL172 isoform. Br J Cancer. 2015;113:336–344. doi: 10.1038/bjc.2015.189 26035699
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