Skip to main content

Functional Contributions of Prefoldin to Gene Expression

  • Chapter
  • First Online:
Prefoldins: the new chaperones

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1106))

Abstract

Prefoldin is a co-chaperone that evolutionarily originates in archaea, is universally present in all eukaryotes and acts as a co-chaperone by facilitating the supply of unfolded or partially folded substrates to class II chaperonins. Eukaryotic prefoldin is known mainly for its functional relevance in the cytoplasmic folding of actin and tubulin monomers during cytoskeleton assembly. However, the role of prefoldin in chaperonin-mediated folding is not restricted to cytoskeleton components, but extends to both the assembly of other cytoplasmic complexes and the maintenance of functional proteins by avoiding protein aggregation and facilitating proteolytic degradation. Evolution has favoured the diversification of prefoldin subunits, and has allowed the so-called prefoldin-like complex, with specialised functions, to appear. Subunits of both canonical and prefoldin-like complexes have also been found in the nucleus of yeast and metazoan cells, where they have been functionally connected with different gene expression steps. Plant prefoldin has also been detected in the nucleus and is physically associated with a gene regulator. Here we summarise information available on the functional involvement of prefoldin in gene expression, and discuss the implications of these results for the relationship between prefoldin structure and function.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Abe A et al (2013) Prefoldin plays a role as a clearance factor in preventing proteasome inhibitor-induced protein aggregation. J Biol Chem 288(39):27764–27776

    Article  CAS  Google Scholar 

  • Amorim AF et al (2017) Absence of Gim proteins, but not GimC complex, alters stress-induced transcription. Biochim Biophys Acta 1860(7):773–781

    Article  CAS  Google Scholar 

  • Boulon S et al (2010) HSP90 and its R2TP/Prefoldin-like cochaperone are involved in the cytoplasmic assembly of RNA polymerase II. Mol Cell 39(6):912–924

    Article  CAS  Google Scholar 

  • Cao S et al (2008) Subunit 1 of the prefoldin chaperone complex is required for lymphocyte development and function. J Immunol 181(1):476–484

    Article  CAS  Google Scholar 

  • Chang LS et al (2012) Epstein-Barr virus BGLF4 kinase downregulates NF-kappaB transactivation through phosphorylation of coactivator UXT. J Virol 86(22):12176–12186

    Article  CAS  Google Scholar 

  • Chávez S, Puerto-Camacho P (2016) Prefoldins. In eLS, John Wiley & Sons, Ltd (Ed.). https://doi.org/10.1002/9780470015902.a0026334

  • Chen S et al (2013) Regulation of the transcriptional activation of the androgen receptor by the UXT-binding protein VHL. Biochem J 456(1):55–66

    Article  CAS  Google Scholar 

  • Cloutier P et al (2017) R2TP/Prefoldin-like component RUVBL1/RUVBL2 directly interacts with ZNHIT2 to regulate assembly of U5 small nuclear ribonucleoprotein. Nat Commun 8:15615

    Article  CAS  Google Scholar 

  • Collins SR et al (2007) Functional dissection of protein complexes involved in yeast chromosome biology using a genetic interaction map. Nature 446(7137):806–810

    Article  CAS  Google Scholar 

  • Comyn SA et al (2016) Prefoldin promotes proteasomal degradation of cytosolic proteins with missense mutations by maintaining substrate solubility. PLoS Genet 12(7):e1006184

    Article  Google Scholar 

  • Costanzo M et al (2010) The genetic landscape of a cell. Science 327(5964):425–431

    Article  CAS  Google Scholar 

  • Delgehyr N et al (2012) Drosophila Mgr, a prefoldin subunit cooperating with von Hippel Lindau to regulate tubulin stability. Proc Natl Acad Sci U S A 109(15):5729–5734

    Article  CAS  Google Scholar 

  • Delgermaa L et al (2004) Subcellular localization of RPB5-mediating protein and its putative functional partner. Mol Cell Biol 24(19):8556–8566

    Article  CAS  Google Scholar 

  • Djouder N et al (2007) S6K1-mediated disassembly of mitochondrial URI/PP1gamma complexes activates a negative feedback program that counters S6K1 survival signaling. Mol Cell 28(1):28–40

    Article  CAS  Google Scholar 

  • Dorjsuren D et al (1998) RMP, a novel RNA polymerase II subunit 5-interacting protein, counteracts transactivation by hepatitis B virus X protein. Mol Cell Biol 18(12):7546–7555

    Article  CAS  Google Scholar 

  • Enunlu I, Ozansoy M, Basak AN (2011) Alfa-class prefoldin protein UXT is a novel interacting partner of Amyotrophic Lateral Sclerosis 2 (Als2) protein. Biochem Biophys Res Commun 413(3):471–475

    Article  CAS  Google Scholar 

  • Fandrich M et al (2000) Observation of the noncovalent assembly and disassembly pathways of the chaperone complex MtGimC by mass spectrometry. Proc Natl Acad Sci U S A 97(26):14151–14155

    Article  CAS  Google Scholar 

  • Fujioka Y et al (2001) MM-1, a c-Myc-binding protein, is a candidate for a tumor suppressor in leukemia/lymphoma and tongue cancer. J Biol Chem 276(48):45137–45144

    Article  CAS  Google Scholar 

  • Geissler S, Siegers K, Schiebel E (1998) A novel protein complex promoting formation of functional alpha- and gamma-tubulin. EMBO J 17(4):952–966

    Article  CAS  Google Scholar 

  • Gottesfeld JM, Forbes DJ (1997) Mitotic repression of the transcriptional machinery. Trends Biochem Sci 22(6):197–202

    Article  CAS  Google Scholar 

  • Gstaiger M et al (2003) Control of nutrient-sensitive transcription programs by the unconventional prefoldin URI. Science 302(5648):1208–1212

    Article  CAS  Google Scholar 

  • Gu Y et al (2008) Prefoldin 6 is required for normal microtubule dynamics and organization in Arabidopsis. Proc Natl Acad Sci U S A 105(46):18064–18069

    Article  CAS  Google Scholar 

  • Hagio Y et al (2006) Distinct localizations and repression activities of MM-1 isoforms toward c-Myc. J Cell Biochem 97(1):145–155

    Article  CAS  Google Scholar 

  • Hennecke S et al (2015) Prevalence of the prefoldin subunit 5 gene deletion in canine mammary tumors. PLoS One 10(7):e0131280

    Article  Google Scholar 

  • Hintermair C et al (2016) Specific threonine-4 phosphorylation and function of RNA polymerase II CTD during M phase progression. Sci Rep 6:27401

    Article  CAS  Google Scholar 

  • Horejsi Z et al (2010) CK2 phospho-dependent binding of R2TP complex to TEL2 is essential for mTOR and SMG1 stability. Mol Cell 39(6):839–850

    Article  CAS  Google Scholar 

  • Kida H et al (2008) Structural and molecular characterization of the prefoldin beta subunit from Thermococcus strain KS-1. J Mol Biol 383(3):465–474

    Article  CAS  Google Scholar 

  • Kim SY et al (2008) Hepatitis B virus X protein enhances NFkappaB activity through cooperating with VBP1. BMB Rep 41(2):158–163

    Article  CAS  Google Scholar 

  • Kimura Y et al (2007) MM-1 facilitates degradation of c-Myc by recruiting proteasome and a novel ubiquitin E3 ligase. Int J Oncol 31(4):829–836

    CAS  PubMed  Google Scholar 

  • Lee Y et al (2011) Prefoldin 5 is required for normal sensory and neuronal development in a murine model. J Biol Chem 286(1):726–736

    Article  CAS  Google Scholar 

  • Leroux MR (1999) MtGimC, a novel archaeal chaperone related to the eukaryotic chaperonin cofactor GimC/prefoldin. EMBO J 18(23):6730–6743

    Article  CAS  Google Scholar 

  • Locascio A, Blazquez MA, Alabadi D (2013) Dynamic regulation of cortical microtubule organization through prefoldin-DELLA interaction. Curr Biol 23(9):804–809

    Article  CAS  Google Scholar 

  • Lundin VF et al (2008) Efficient chaperone-mediated tubulin biogenesis is essential for cell division and cell migration in C. elegans. Dev Biol 313(1):320–334

    Article  CAS  Google Scholar 

  • Ma HC et al (2008) Hepatitis C virus ARFP/F protein interacts with cellular MM-1 protein and enhances the gene trans-activation activity of c-Myc. J Biomed Sci 15(4):417–425

    Article  CAS  Google Scholar 

  • Markus SM et al (2002) Identification and characterization of ART-27, a novel coactivator for the androgen receptor N terminus. Mol Biol Cell 13(2):670–682

    Article  CAS  Google Scholar 

  • McGilvray R, Walker M, Bartholomew C (2007) UXT interacts with the transcriptional repressor protein EVI1 and suppresses cell transformation. FEBS J 274(15):3960–3971

    Article  CAS  Google Scholar 

  • Millan-Zambrano G et al (2013) The prefoldin complex regulates chromatin dynamics during transcription elongation. PLoS Genet 9(9):e1003776

    Article  CAS  Google Scholar 

  • Miron-Garcia MC et al (2013) The prefoldin bud27 mediates the assembly of the eukaryotic RNA polymerases in an rpb5-dependent manner. PLoS Genet 9(2):e1003297

    Article  CAS  Google Scholar 

  • Miron-Garcia MC et al (2014) The yeast prefoldin-like URI-orthologue Bud27 associates with the RSC nucleosome remodeler and modulates transcription. Nucleic Acids Res 42(15):9666–9676

    Article  CAS  Google Scholar 

  • Mita P et al (2013) Analysis of URI nuclear interaction with RPB5 and components of the R2TP/prefoldin-like complex. PLoS One 8(5):e63879

    Article  CAS  Google Scholar 

  • Mita P et al (2016) URI regulates KAP1 phosphorylation and transcriptional repression via PP2A phosphatase in prostate cancer cells. J Biol Chem 291(49):25516–25528

    Article  CAS  Google Scholar 

  • Mori K et al (1998) MM-1, a novel c-Myc-associating protein that represses transcriptional activity of c-Myc. J Biol Chem 273(45):29794–29800

    Article  CAS  Google Scholar 

  • Mousnier A et al (2007) von Hippel Lindau binding protein 1-mediated degradation of integrase affects HIV-1 gene expression at a postintegration step. Proc Natl Acad Sci U S A 104(34):13615–13620

    Article  CAS  Google Scholar 

  • Narita R et al (2012) Rabring7 degrades c-Myc through complex formation with MM-1. PLoS One 7(7):e41891

    Article  CAS  Google Scholar 

  • Pajares MA (2017) PDRG1 at the interface between intermediary metabolism and oncogenesis. World J Biol Chem 8(4):175–186

    Article  Google Scholar 

  • Perez C et al (2016) The oncogene PDRG1 Is an interaction target of methionine adenosyltransferases. PLoS One 11(8):e0161672

    Article  Google Scholar 

  • Rodriguez-Milla MA, Salinas J (2009) Prefoldins 3 and 5 play an essential role in Arabidopsis tolerance to salt stress. Mol Plant 2(3):526–534

    Article  CAS  Google Scholar 

  • Rommelaere H et al (2001) Prefoldin recognition motifs in the nonhomologous proteins of the actin and tubulin families. J Biol Chem 276(44):41023–41028

    Article  CAS  Google Scholar 

  • Sanchez-Morgan N et al (2017) UXT Is a LOX-PP interacting protein that modulates estrogen receptor alpha activity in breast cancer cells. J Cell Biochem 118(8):2347–2356

    Article  CAS  Google Scholar 

  • Satou A et al (2001) 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 276(49):46562–46567

    Article  CAS  Google Scholar 

  • Siegert R et al (2000) Structure of the molecular chaperone prefoldin: unique interaction of multiple coiled coil tentacles with unfolded proteins. Cell 103(4):621–632

    Article  CAS  Google Scholar 

  • Sorgjerd KM et al (2013) Human prefoldin inhibits amyloid-beta (Abeta) fibrillation and contributes to formation of nontoxic Abeta aggregates. Biochemistry 52(20):3532–3542

    Article  CAS  Google Scholar 

  • Sun S et al (2007) UXT is a novel and essential cofactor in the NF-kappaB transcriptional enhanceosome. J Cell Biol 178(2):231–244

    Article  CAS  Google Scholar 

  • Takano M et al (2014) Prefoldin prevents aggregation of alpha-synuclein. Brain Res 1542:186–194

    Article  CAS  Google Scholar 

  • Taneja SS et al (2004) ART-27, an androgen receptor coactivator regulated in prostate development and cancer. J Biol Chem 279(14):13944–13952

    Article  CAS  Google Scholar 

  • Tashiro E et al (2013) Prefoldin protects neuronal cells from polyglutamine toxicity by preventing aggregation formation. J Biol Chem 288(27):19958–19972

    Article  CAS  Google Scholar 

  • Tummala KS et al (2014) Inhibition of de novo NAD(+) synthesis by oncogenic URI causes liver tumorigenesis through DNA damage. Cancer Cell 26(6):826–839

    Article  CAS  Google Scholar 

  • Vainberg IE et al (1998) Prefoldin, a chaperone that delivers unfolded proteins to cytosolic chaperonin. Cell 93(5):863–873

    Article  CAS  Google Scholar 

  • Vernekar DV, Bhargava P (2015) Yeast Bud27 modulates the biogenesis of Rpc128 and Rpc160 subunits and the assembly of RNA polymerase III. Biochim Biophys Acta 1849(11):1340–1353

    Article  CAS  Google Scholar 

  • Wang P et al (2015) PFDN1, an indicator for colorectal cancer prognosis, enhances tumor cell proliferation and motility through cytoskeletal reorganization. Med Oncol 32(12):264

    Article  Google Scholar 

  • Wang D et al (2017) Prefoldin 1 promotes EMT and lung cancer progression by suppressing cyclin A expression. Oncogene 36(7):885–898

    Article  CAS  Google Scholar 

  • Yamane T et al (2015) Deficiency of spermatogenesis and reduced expression of spermatogenesis-related genes in prefoldin 5-mutant mice. Biochem Biophys Rep 1:52–61

    PubMed  PubMed Central  Google Scholar 

  • Yang J et al (2009) The single-macro domain protein LRP16 is an essential cofactor of androgen receptor. Endocr Relat Cancer 16(1):139–153

    Article  CAS  Google Scholar 

  • Yoshida T et al (2008) Negative regulation of the Wnt signal by MM-1 through inhibiting expression of the wnt4 gene. Exp Cell Res 314(6):1217–1228

    Article  CAS  Google Scholar 

  • Zhang Y et al (2016) Prefoldin and Pins synergistically regulate asymmetric division and suppress dedifferentiation. Sci Rep 6:23735

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by Grants from the Spanish Ministry of Economy and Competitiveness (MINECO) and the European Regional Development Fund (ERDF): BFU2016-77728-C3-3-P. We also acknowledge the support from the Andalusian Government and ERDF (Grant P12-BIO-1938 MO). L.P.-B. is a recipient of an FPI contract from Junta de Andalucía. We thank Helen Warburton for editing the English.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Sebastián Chávez .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Payán-Bravo, L., Peñate, X., Chávez, S. (2018). Functional Contributions of Prefoldin to Gene Expression. In: Djouder, N. (eds) Prefoldins: the new chaperones. Advances in Experimental Medicine and Biology, vol 1106. Springer, Cham. https://doi.org/10.1007/978-3-030-00737-9_1

Download citation

Publish with us

Policies and ethics