Skip to main content

Functions of the Hsp90-Binding FKBP Immunophilins

Part of the Subcellular Biochemistry book series (SCBI,volume 78)

Abstract

Hsp90 functionally interacts with a broad array of client proteins, but in every case examined Hsp90 is accompanied by one or more co-chaperones. One class of co-chaperone contains a tetratricopeptide repeat domain that targets the co-chaperone to the C-terminal region of Hsp90. Within this class are Hsp90-binding peptidylprolyl isomerases, most of which belong to the FK506-binding protein (FKBP) family. Despite the common association of FKBP co-chaperones with Hsp90, it is now clear that the client protein influences, and is influenced by, the particular FKBP bound to Hsp90. Examples include Xap2 in aryl hydrocarbon receptor complexes and FKBP52 in steroid receptor complexes. In this chapter, we discuss the known functional roles played by FKBP co-chaperones and, where possible, relate distinctive functions to structural differences between FKBP members.

Keywords

  • Immunophilin
  • FKBP
  • Hsp90
  • Steroid hormone receptor

This is a preview of subscription content, access via your institution.

Buying options

Chapter
USD   29.95
Price excludes VAT (USA)
  • DOI: 10.1007/978-3-319-11731-7_2
  • Chapter length: 34 pages
  • Instant PDF download
  • Readable on all devices
  • Own it forever
  • Exclusive offer for individuals only
  • Tax calculation will be finalised during checkout
eBook
USD   169.00
Price excludes VAT (USA)
  • ISBN: 978-3-319-11731-7
  • Instant PDF download
  • Readable on all devices
  • Own it forever
  • Exclusive offer for individuals only
  • Tax calculation will be finalised during checkout
Softcover Book
USD   219.99
Price excludes VAT (USA)
Hardcover Book
USD   219.99
Price excludes VAT (USA)
Fig. 2.1
Fig. 2.2
Fig. 2.3

References

  • Abukhdeir AM, Vitolo MI, Argani P, De Marzo AM, Karakas B, Konishi H, Gustin JP, Lauring J, Garay JP, Pendleton C, Konishi Y, Blair BG, Brenner K, Garrett-Mayer E, Carraway H, Bachman KE, Park BH (2008) Tamoxifen-stimulated growth of breast cancer due to p21 loss. Proc Natl Acad Sci U S A 105(1):288–293

    CAS  PubMed Central  PubMed  Google Scholar 

  • Bai X, Ma D, Liu A, Shen X, Wang QJ, Liu Y, Jiang Y (2007) Rheb activates mTOR by antagonizing its endogenous inhibitor, FKBP38. Science 318(5852):977–980

    CAS  PubMed  Google Scholar 

  • Banasavadi-Siddegowda YK, Mai J, Fan Y, Bhattacharya S, Giovannucci DR, Sanchez ER, Fischer G, Wang X (2011) FKBP38 peptidylprolyl isomerase promotes the folding of cystic fibrosis transmembrane conductance regulator in the endoplasmic reticulum. J Biol Chem 286(50):43071–43080

    CAS  PubMed Central  PubMed  Google Scholar 

  • Barent RL, Nair SC, Carr DC, Ruan Y, Rimerman RA, Fulton J, Zhang Y, Smith DF (1998) Analysis of FKBP51/FKBP52 chimeras and mutants for Hsp90 binding and association with progesterone receptor complexes. Mol Endocrinol 12(3):342–354

    CAS  PubMed  Google Scholar 

  • Barnham KJ, Bush AI (2008) Metals in Alzheimer’s and Parkinson’s diseases. Curr Opin Chem Biol 12(2):222–228. doi:10.1016/j.cbpa.2008.02.019

    CAS  PubMed  Google Scholar 

  • Barth S, Edlich F, Berchner-Pfannschmidt U, Gneuss S, Jahreis G, Hasgall PA, Fandrey J, Wenger RH, Camenisch G (2009) Hypoxia-inducible factor prolyl-4-hydroxylase PHD2 protein abundance depends on integral membrane anchoring of FKBP38. J Biol Chem 284(34):23046–23058

    CAS  PubMed Central  PubMed  Google Scholar 

  • Baughman G, Wiederrecht GJ, Campbell NF, Martin MM, Bourgeois S (1995) FKBP51, a novel T-cell-specific immunophilin capable of calcineurin inhibition. Mol Cell Biol 15(8):4395–4402

    CAS  PubMed Central  PubMed  Google Scholar 

  • Benedict JC, Lin TM, Loeffler IK, Peterson RE, Flaws JA (2000) Physiological role of the aryl hydrocarbon receptor in mouse ovary development. Toxicol Sci 56(2):382–388

    CAS  PubMed  Google Scholar 

  • Berg P, Pongratz I (2002) Two parallel pathways mediate cytoplasmic localization of the dioxin (aryl hydrocarbon) receptor. J Biol Chem 277(35):32310–32319

    CAS  PubMed  Google Scholar 

  • Binder EB (2009) The role of FKBP5, a co-chaperone of the glucocorticoid receptor in the pathogenesis and therapy of affective and anxiety disorders. Psychoneuroendocrinology 34(Suppl 1):S186–195. doi:10.1016/j.psyneuen.2009.05.021

    CAS  PubMed  Google Scholar 

  • Binder EB, Salyakina D, Lichtner P, Wochnik GM, Ising M, Putz B, Papiol S, Seaman S, Lucae S, Kohli MA, Nickel T, Kunzel HE, Fuchs B, Majer M, Pfennig A, Kern N, Brunner J, Modell S, Baghai T, Deiml T, Zill P, Bondy B, Rupprecht R, Messer T, Kohnlein O, Dabitz H, Bruckl T, Muller N, Pfister H, Lieb R, Mueller JC, Lohmussaar E, Strom TM, Bettecken T, Meitinger T, Uhr M, Rein T, Holsboer F, Muller-Myhsok B (2004) Polymorphisms in FKBP5 are associated with increased recurrence of depressive episodes and rapid response to antidepressant treatment. Nat Genet 36(12):1319–1325

    CAS  PubMed  Google Scholar 

  • Binder EB, Bradley RG, Liu W, Epstein MP, Deveau TC, Mercer KB, Tang Y, Gillespie CF, Heim CM, Nemeroff CB, Schwartz AC, Cubells JF, Ressler KJ (2008) Association of FKBP5 polymorphisms and childhood abuse with risk of posttraumatic stress disorder symptoms in adults. JAMA 299(11):1291–1305

    CAS  PubMed Central  PubMed  Google Scholar 

  • Blair LJ, Nordhues BA, Hill SE, Scaglione KM, O’Leary JC 3rd, Fontaine SN, Breydo L, Zhang B, Li P, Wang L, Cotman C, Paulson HL, Muschol M, Uversky VN, Klengel T, Binder EB, Kayed R, Golde TE, Berchtold N, Dickey CA (2013) Accelerated neurodegeneration through chaperone-mediated oligomerization of tau. J Clin Invest 123(10):4158–4169. doi:10.1172/JCI69003

    CAS  PubMed Central  PubMed  Google Scholar 

  • Blatch GL, Lassle M (1999) The tetratricopeptide repeat: a structural motif mediating protein-protein interactions. Bioessays 21(11):932–939

    CAS  PubMed  Google Scholar 

  • Bose S, Weikl T, Bugl H, Buchner J (1996) Chaperone function of Hsp90-associated proteins. Science 274(5293):1715–1717

    CAS  PubMed  Google Scholar 

  • Bouwmeester T, Bauch A, Ruffner H, Angrand PO, Bergamini G, Croughton K, Cruciat C, Eberhard D, Gagneur J, Ghidelli S, Hopf C, Huhse B, Mangano R, Michon AM, Schirle M, Schlegl J, Schwab M, Stein MA, Bauer A, Casari G, Drewes G, Gavin AC, Jackson DB, Joberty G, Neubauer G, Rick J, Kuster B, Superti-Furga G (2004) A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway. Nat Cell Biol 6(2):97–105

    CAS  PubMed  Google Scholar 

  • Bracher A, Kozany C, Hahle A, Wild P, Zacharias M, Hausch F (2013) Crystal structures of the free and ligand-bound FK1-FK2 domain segment of FKBP52 reveal a flexible inter-domain hinge. J Mol Biol 425(22):4134–4144

    CAS  PubMed  Google Scholar 

  • Broemer M, Krappmann D, Scheidereit C (2004) Requirement of Hsp90 activity for IkappaB kinase (IKK) biosynthesis and for constitutive and inducible IKK and NF-kappaB activation. Oncogene 23(31):5378–5386

    CAS  PubMed  Google Scholar 

  • Brown EJ, Albers MW, Shin TB, Ichikawa K, Keith CT, Lane WS, Schreiber SL (1994) A mammalian protein targeted by G1-arresting rapamycin-receptor complex. Nature 369(6483):756–758

    CAS  PubMed  Google Scholar 

  • Bublik DR, Scolz M, Triolo G, Monte M, Schneider C (2010) Human GTSE-1 regulates p21(CIP1/WAF1) stability conferring resistance to paclitaxel treatment. J Biol Chem 285(8):5274–5281

    CAS  PubMed Central  PubMed  Google Scholar 

  • Buzon V, Carbo LR, Estruch SB, Fletterick RJ, Estebanez-Perpina E (2012) A conserved surface on the ligand binding domain of nuclear receptors for allosteric control. Mol Cell Endocrinol 348(2):394–402

    CAS  PubMed  Google Scholar 

  • Cai W, Kramarova TV, Berg P, Korbonits M, Pongratz I (2011) The immunophilin-like protein XAP2 is a negative regulator of estrogen signaling through interaction with estrogen receptor alpha. PLoS One 6(10):e25201

    CAS  PubMed Central  PubMed  Google Scholar 

  • Cao W, Konsolaki M (2011) FKBP immunophilins and Alzheimer’s disease: a chaperoned affair. J Biosci 36(3):493–498

    CAS  PubMed  Google Scholar 

  • Carver LA, LaPres JJ, Jain S, Dunham EE, Bradfield CA (1998) Characterization of the Ah receptor-associated protein, ARA9. J Biol Chem 273(50):33580–33587

    CAS  PubMed  Google Scholar 

  • Chambraud B, Rouviere-Fourmy N, Radanyi C, Hsiao K, Peattie DA, Livingston DJ, Baulieu EE (1993) Overexpression of p59-HBI (FKBP59), full length and domains, and characterization of PPlase activity. Biochem Biophys Res Commun 196(1):160–166

    CAS  PubMed  Google Scholar 

  • Chambraud B, Radanyi C, Camonis JH, Shazand K, Rajkowski K, Baulieu EE (1996) FAP48, a new protein that forms specific complexes with both immunophilins FKBP59 and FKBP12. Prevention by the immunosuppressant drugs FK506 and rapamycin. J Biol Chem 271(51):32923–32929

    CAS  PubMed  Google Scholar 

  • Chambraud B, Belabes H, Fontaine-Lenoir V, Fellous A, Baulieu EE (2007) The immunophilin FKBP52 specifically binds to tubulin and prevents microtubule formation. FASEB J 21(11):2787–2797. doi:10.1096/fj.06-7667com

    CAS  PubMed  Google Scholar 

  • Chambraud B, Sardin E, Giustiniani J, Dounane O, Schumacher M, Goedert M, Baulieu EE (2010) A role for FKBP52 in Tau protein function. Proc Natl Acad Sci U S A 107(6):2658–2663

    CAS  PubMed Central  PubMed  Google Scholar 

  • Cheung-Flynn J, Prapapanich V, Cox MB, Riggs DL, Suarez-Quian C, Smith DF (2005) Physiological role for the cochaperone FKBP52 in androgen receptor signaling. Mol Endocrinol 19(6):1654–1666

    CAS  PubMed  Google Scholar 

  • Cho A, Ko HW, Eggenschwiler JT (2008) FKBP8 cell-autonomously controls neural tube patterning through a Gli2- and Kif3a-dependent mechanism. Dev Biol 321(1):27–39

    CAS  PubMed  Google Scholar 

  • Choi BH, Feng L, Yoon HS (2010) FKBP38 protects Bcl-2 from caspase-dependent degradation. J Biol Chem 285(13):9770–9779

    CAS  PubMed Central  PubMed  Google Scholar 

  • Chu K, Teele N, Dewey MW, Albright N, Dewey WC (2004) Computerized video time lapse study of cell cycle delay and arrest, mitotic catastrophe, apoptosis and clonogenic survival in irradiated 14-3-3sigma and CDKN1A (p21) knockout cell lines. Radiat Res 162(3):270–286

    CAS  PubMed  Google Scholar 

  • Cluning C, Ward BK, Rea SL, Arulpragasam A, Fuller PJ, Ratajczak T (2013) The helix 1–3 loop in the glucocorticoid receptor LBD is a regulatory element for FKBP cochaperones. Mol Endocrinol 27(7):1020–1035

    CAS  PubMed  Google Scholar 

  • Colo GP, Rubio MF, Nojek IM, Werbajh SE, Echeverria PC, Alvarado CV, Nahmod VE, Galigniana MD, Costas MA (2008) The p160 nuclear receptor co-activator RAC3 exerts an anti-apoptotic role through a cytoplasmatic action. Oncogene 27(17):2430–2444

    CAS  PubMed  Google Scholar 

  • Cox MB, Riggs DL, Hessling M, Schumacher F, Buchner J, Smith DF (2007) FK506-binding protein 52 phosphorylation: a potential mechanism for regulating steroid hormone receptor activity. Mol Endocrinol 21(12):2956–2967

    CAS  PubMed  Google Scholar 

  • Crabb SJ, Patsios D, Sauerbrei E, Ellis PM, Arnold A, Goss G, Leighl NB, Shepherd FA, Powers J, Seymour L, Laurie SA (2009) Tumor cavitation: impact on objective response evaluation in trials of angiogenesis inhibitors in non-small-cell lung cancer. J Clin Oncol 27(3):404–410

    CAS  PubMed  Google Scholar 

  • Crackower MA, Kolas NK, Noguchi J, Sarao R, Kikuchi K, Kaneko H, Kobayashi E, Kawai Y, Kozieradzki I, Landers R, Mo R, Hui CC, Nieves E, Cohen PE, Osborne LR, Wada T, Kunieda T, Moens PB, Penninger JM (2003) Essential role of Fkbp6 in male fertility and homologous chromosome pairing in meiosis. Science 300(5623):1291–1295

    CAS  PubMed Central  PubMed  Google Scholar 

  • Dahmer MK, Housley PR, Pratt WB (1984) Effects of molybdate and endogenous inhibitors on steroid-receptor inactivation, transformation, and translocation. Annu Rev Physiol 46:67–81.

    CAS  PubMed  Google Scholar 

  • Daikoku T, Tranguch S, Friedman DB, Das SK, Smith DF, Dey SK (2005) Proteomic analysis identifies immunophilin FK506 binding protein 4 (FKBP52) as a downstream target of Hoxa10 in the periimplantation mouse uterus. Mol Endocrinol 19(3):683–697

    CAS  PubMed  Google Scholar 

  • Davies TH, Ning YM, Sanchez ER (2002) A new first step in activation of steroid receptors: hormone-induced switching of FKBP51 and FKBP52 immunophilins. J Biol Chem 277(7):4597–4600

    CAS  PubMed  Google Scholar 

  • Davies TH, Ning YM, Sanchez ER (2005) Differential control of glucocorticoid receptor hormone-binding function by tetratricopeptide repeat (TPR) proteins and the immunosuppressive ligand FK506. Biochemistry 44(6):2030–2038

    CAS  PubMed  Google Scholar 

  • De Leon JT, Iwai A, Feau C, Garcia Y, Balsiger HA, Storer CL, Suro RM, Garza KM, Lee S, Kim YS, Chen Y, Ning YM, Riggs DL, Fletterick RJ, Guy RK, Trepel JB, Neckers LM, Cox MB (2011) Targeting the regulation of androgen receptor signaling by the heat shock protein 90 cochaperone FKBP52 in prostate cancer cells. Proc Natl Acad Sci U S A 108(29):11878–11883. doi:10.1073/pnas.1105160108

    CAS  PubMed Central  PubMed  Google Scholar 

  • Denny WB, Valentine DL, Reynolds PD, Smith DF, Scammell JG (2000) Squirrel monkey immunophilin FKBP51 is a potent inhibitor of glucocorticoid receptor binding. Endocrinology 141(11):4107–4113

    CAS  PubMed  Google Scholar 

  • Denny WB, Prapapanich V, Smith DF, Scammell JG (2005) Structure-function analysis of squirrel monkey FK506-binding protein 51, a potent inhibitor of glucocorticoid receptor activity. Endocrinology 146(7):3194–3201

    CAS  PubMed  Google Scholar 

  • Dittmar KD, Hutchison KA, Owens-Grillo JK, Pratt WB (1996) Reconstitution of the steroid receptor hsp90 heterocomplex assembly system of rabbit reticulocyte lysate. J Biol Chem 271(22):12833–12839

    CAS  PubMed  Google Scholar 

  • Dolinski K, Muir S, Cardenas M, Heitman J (1997) All cyclophilins and FK506 binding proteins are, individually and collectively, dispensable for viability in Saccharomyces cerevisiae. Proc Natl Acad Sci U S A 94(24):13093–13098

    CAS  PubMed Central  PubMed  Google Scholar 

  • Donley C, McClelland K, McKeen HD, Nelson L, Yakkundi A, Jithesh PV, Burrows J, McClements L, Valentine A, Prise KM, McCarthy HO, Robson T (2013) Identification of RBCK1 as a novel regulator of FKBPL: implications for tumor growth and response to tamoxifen. Oncogene 5(10):306

    Google Scholar 

  • Drago D, Bolognin S, Zatta P (2008) Role of metal ions in the abeta oligomerization in Alzheimer’s disease and in other neurological disorders. Curr Alzheimer Res 5(6):500–507

    CAS  PubMed  Google Scholar 

  • Echeverria PC, Mazaira G, Erlejman A, Gomez-Sanchez C, Piwien Pilipuk G, Galigniana MD (2009) Nuclear import of the glucocorticoid receptor-hsp90 complex through the nuclear pore complex is mediated by its interaction with Nup62 and importin beta. Mol Cell Biol 29(17):4788–4797

    CAS  PubMed Central  PubMed  Google Scholar 

  • Edlich F, Lucke C (2011) From cell death to viral replication: the diverse functions of the membrane-associated FKBP38. Curr Opin Pharmacol 11(4):348–353

    CAS  PubMed  Google Scholar 

  • Edlich F, Weiwad M, Erdmann F, Fanghanel J, Jarczowski F, Rahfeld JU, Fischer G (2005) Bcl-2 regulator FKBP38 is activated by Ca2+/calmodulin. EMBO J 24(14):2688–2699

    CAS  PubMed Central  PubMed  Google Scholar 

  • Edlich F, Weiwad M, Wildemann D, Jarczowski F, Kilka S, Moutty MC, Jahreis G, Lucke C, Schmidt W, Striggow F, Fischer G (2006) The specific FKBP38 inhibitor N-(Nʹ,Nʹ-dimethylcarboxamidomethyl)cycloheximide has potent neuroprotective and neurotrophic properties in brain ischemia. J Biol Chem 281(21):14961–14970

    CAS  PubMed  Google Scholar 

  • Edlich F, Erdmann F, Jarczowski F, Moutty MC, Weiwad M, Fischer G (2007a) The Bcl-2 regulator FKBP38-calmodulin-Ca2+ is inhibited by Hsp90. J Biol Chem 282(21):15341–15348

    CAS  Google Scholar 

  • Edlich F, Maestre-Martinez M, Jarczowski F, Weiwad M, Moutty MC, Malesevic M, Jahreis G, Fischer G, Lucke C (2007b) A novel calmodulin-Ca2+ target recognition activates the Bcl-2 regulator FKBP38. J Biol Chem 282(50):36496–36504

    CAS  Google Scholar 

  • Elbi C, Walker DA, Romero G, Sullivan WP, Toft DO, Hager GL, DeFranco DB (2004) Molecular chaperones function as steroid receptor nuclear mobility factors. Proc Natl Acad Sci U S A 101(9):2876–2881

    CAS  PubMed Central  PubMed  Google Scholar 

  • Erlejman AG, Lagadari M, Toneatto J, Piwien-Pilipuk G, Galigniana MD (2014) Regulatory role of the 90-kDa-heat-shock protein (Hsp90) and associated factors on gene expression. Biochim Biophys Acta 1839(2):71–87

    Google Scholar 

  • Estebanez-Perpina E, Arnold LA, Nguyen P, Rodrigues ED, Mar E, Bateman R, Pallai P, Shokat KM, Baxter JD, Guy RK, Webb P, Fletterick RJ (2007) A surface on the androgen receptor that allosterically regulates coactivator binding. Proc Natl Acad Sci U S A 104(41):16074–16079

    CAS  PubMed Central  PubMed  Google Scholar 

  • Febbo PG, Lowenberg M, Thorner AR, Brown M, Loda M, Golub TR (2005) Androgen mediated regulation and functional implications of fkbp51 expression in prostate cancer. J Urol 173(5):1772–1777

    CAS  PubMed  Google Scholar 

  • Fernandez-Salguero P, Pineau T, Hilbert DM, McPhail T, Lee SS, Kimura S, Nebert DW, Rudikoff S, Ward JM, Gonzalez FJ (1995) Immune system impairment and hepatic fibrosis in mice lacking the dioxin-binding Ah receptor. Science 268(5211):722–726

    CAS  PubMed  Google Scholar 

  • Fernandez-Salguero PM, Hilbert DM, Rudikoff S, Ward JM, Gonzalez FJ (1996) Aryl-hydrocarbon receptor-deficient mice are resistant to 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced toxicity. Toxicol Appl Pharmacol 140(1):173–179

    CAS  PubMed  Google Scholar 

  • Fusco D, Vargiolu M, Vidone M, Mariani E, Pennisi LF, Bonora E, Capellari S, Dirnberger D, Baumeister R, Martinelli P, Romeo G (2010) The RET51/FKBP52 complex and its involvement in Parkinson disease. Hum Mol Genet 19(14):2804–2816. doi:10.1093/hmg/ddq181

    CAS  PubMed  Google Scholar 

  • Galigniana MD, Radanyi C, Renoir JM, Housley PR, Pratt WB (2001) Evidence that the peptidylprolyl isomerase domain of the hsp90-binding immunophilin FKBP52 is involved in both dynein interaction and glucocorticoid receptor movement to the nucleus. J Biol Chem 276(18):14884–14889

    CAS  PubMed  Google Scholar 

  • Galigniana MD, Harrell JM, Murphy PJ, Chinkers M, Radanyi C, Renoir JM, Zhang M, Pratt WB (2002) Binding of hsp90-associated immunophilins to cytoplasmic dynein: direct binding and in vivo evidence that the peptidylprolyl isomerase domain is a dynein interaction domain. Biochemistry 41(46):13602–13610

    CAS  PubMed  Google Scholar 

  • Galigniana MD, Harrell JM, Housley PR, Patterson C, Fisher SK, Pratt WB (2004a) Retrograde transport of the glucocorticoid receptor in neurites requires dynamic assembly of complexes with the protein chaperone hsp90 and is linked to the CHIP component of the machinery for proteasomal degradation. Brain Res Mol Brain Res 123(1–2):27–36

    CAS  Google Scholar 

  • Galigniana MD, Harrell JM, O’Hagen HM, Ljungman M, Pratt WB (2004b) Hsp90-binding immunophilins link p53 to dynein during p53 transport to the nucleus. J Biol Chem 279(21):22483–22489

    CAS  Google Scholar 

  • Galigniana MD, Echeverria PC, Erlejman AG, Piwien-Pilipuk G (2010a) Role of molecular chaperones and TPR-domain proteins in the cytoplasmic transport of steroid receptors and their passage through the nuclear pore. Nucleus 1(4):299–308

    Google Scholar 

  • Galigniana MD, Erlejman AG, Monte M, Gomez-Sanchez C, Piwien-Pilipuk G (2010b) The hsp90-FKBP52 complex links the mineralocorticoid receptor to motor proteins and persists bound to the receptor in early nuclear events. Mol Cell Biol 30(5):1285–1298

    CAS  Google Scholar 

  • Gallo LI, Ghini AA, Pilipuk GP, Galigniana MD (2007) Differential recruitment of tetratricorpeptide repeat domain immunophilins to the mineralocorticoid receptor influences both heat-shock protein 90-dependent retrotransport and hormone-dependent transcriptional activity. Biochemistry 46(49):14044–14057

    CAS  PubMed  Google Scholar 

  • Geisler M, Kolukisaoglu HU, Bouchard R, Billion K, Berger J, Saal B, Frangne N, Koncz-Kalman Z, Koncz C, Dudler R, Blakeslee JJ, Murphy AS, Martinoia E, Schulz B (2003) TWISTED DWARF1, a unique plasma membrane-anchored immunophilin-like protein, interacts with Arabidopsis multidrug resistance-like transporters AtPGP1 and AtPGP19. Mol Biol Cell 14(10):4238–4249

    CAS  PubMed Central  PubMed  Google Scholar 

  • Geisler M, Girin M, Brandt S, Vincenzetti V, Plaza S, Paris N, Kobae Y, Maeshima M, Billion K, Kolukisaoglu UH, Schulz B, Martinoia E (2004) Arabidopsis immunophilin-like TWD1 functionally interacts with vacuolar ABC transporters. Mol Biol Cell 15(7):3393–3405

    CAS  PubMed Central  PubMed  Google Scholar 

  • Giraudier S, Chagraoui H, Komura E, Barnache S, Blanchet B, LeCouedic JP, Smith DF, Larbret F, Taksin AL, Moreau-Gachelin F, Casadevall N, Tulliez M, Hulin A, Debili N, Vainchenker W (2002) Overexpression of FKBP51 in idiopathic myelofibrosis regulates the growth factor independence of megakaryocyte progenitors. Blood 100(8):2932–2940

    CAS  PubMed  Google Scholar 

  • Giustiniani J, Chambraud B, Sardin E, Dounane O, Guillemeau K, Nakatani H, Paquet D, Kamah A, Landrieu I, Lippens G, Baulieu EE, Tawk M (2014) Immunophilin FKBP52 induces Tau-P301L filamentous assembly in vitro and modulates its activity in a model of tauopathy. Proc Natl Acad Sci U S A 111(12):4584–4589

    CAS  PubMed Central  PubMed  Google Scholar 

  • Goel M, Garcia R, Estacion M, Schilling WP (2001) Regulation of drosophila trpl channels by immunophilin fkbp59. J Biol Chem 276(42):38762–38773

    CAS  PubMed  Google Scholar 

  • Grossmann C, Ruhs S, Langenbruch L, Mildenberger S, Stratz N, Schumann K, Gekle M (2012) Nuclear shuttling precedes dimerization in mineralocorticoid receptor signaling. Chem Biol 19(6):742–751

    CAS  PubMed  Google Scholar 

  • Haelens A, Tanner T, Denayer S, Callewaert L, Claessens F (2007) The hinge region regulates DNA binding, nuclear translocation, and transactivation of the androgen receptor. Cancer Res 67(9):4514–4523. doi:10.1158/0008-5472.CAN-06-1701

    CAS  PubMed  Google Scholar 

  • Hamilton GS, Steiner JP (1998) Immunophilins: beyond immunosuppression. J Med Chem 41(26):5119–5143

    CAS  PubMed  Google Scholar 

  • Han W, Han MR, Kang JJ, Bae JY, Lee JH, Bae YJ, Lee JE, Shin HJ, Hwang KT, Hwang SE, Kim SW, Noh DY (2006) Genomic alterations identified by array comparative genomic hybridization as prognostic markers in tamoxifen-treated estrogen receptor-positive breast cancer. BMC Cancer 6(92):92

    PubMed Central  PubMed  Google Scholar 

  • Hartmann J, Wagner KV, Liebl C, Scharf SH, Wang XD, Wolf M, Hausch F, Rein T, Schmidt U, Touma C, Cheung-Flynn J, Cox MB, Smith DF, Holsboer F, Muller MB, Schmidt MV (2012) The involvement of FK506-binding protein 51 (FKBP5) in the behavioral and neuroendocrine effects of chronic social defeat stress. Neuropharmacology 62(1):332–339. doi:10.1016/j.neuropharm.2011.07.041

    CAS  PubMed  Google Scholar 

  • He Z, Li L, Luan S (2004) Immunophilins and parvulins. Superfamily of peptidyl prolyl isomerases in Arabidopsis. Plant Physiol 134(4):1248–1267

    Google Scholar 

  • Hernandez F, Avila J (2007) Tauopathies. Cell Mol Life Sci 64(17):2219–2233. doi:10.1007/s00018-007-7220-x

    CAS  PubMed  Google Scholar 

  • Hirota Y, Tranguch S, Daikoku T, Hasegawa A, Osuga Y, Taketani Y, Dey SK (2008) Deficiency of immunophilin FKBP52 promotes endometriosis. Am J Pathol 173(6):1747–1757. doi:10.2353/ajpath.2008.080527

    CAS  PubMed Central  PubMed  Google Scholar 

  • Hollingshead BD, Petrulis JR, Perdew GH (2004) The aryl hydrocarbon (Ah) receptor transcriptional regulator hepatitis B virus X-associated protein 2 antagonizes p23 binding to Ah receptor-Hsp90 complexes and is dispensable for receptor function. J Biol Chem 279(44):45652–45661

    CAS  PubMed  Google Scholar 

  • Hubler TR, Denny WB, Valentine DL, Cheung-Flynn J, Smith DF, Scammell JG (2003) The FK506-binding immunophilin FKBP51 is transcriptionally regulated by progestin and attenuates progestin responsiveness. Endocrinology 144(6):2380–2387

    CAS  PubMed  Google Scholar 

  • Jarczowski F, Jahreis G, Erdmann F, Schierhorn A, Fischer G, Edlich F (2009) FKBP36 is an inherent multifunctional glyceraldehyde-3-phosphate dehydrogenase inhibitor. J Biol Chem 284(2):766–773

    CAS  PubMed  Google Scholar 

  • Jascur T, Brickner H, Salles-Passador I, Barbier V, El Khissiin A, Smith B, Fotedar R, Fotedar A (2005) Regulation of p21(WAF1/CIP1) stability by WISp39, a Hsp90 binding TPR protein. Mol Cell 17(2):237–249

    CAS  PubMed  Google Scholar 

  • Jinwal UK, Koren J III, Borysov SI, Schmid AB, Abisambra JF, Blair LJ, Johnson AG, Jones JR, Shults CL, O’Leary JC III, Jin Y, Buchner J, Cox MB, Dickey CA (2010) The Hsp90 cochaperone, FKBP51, increases Tau stability and polymerizes microtubules. J Neurosci 30(2):591–599

    CAS  PubMed Central  PubMed  Google Scholar 

  • Kamphausen T, Fanghanel J, Neumann D, Schulz B, Rahfeld JU (2002) Characterization of Arabidopsis thaliana AtFKBP42 that is membrane-bound and interacts with Hsp90. Plant J 32(3):263–276

    CAS  PubMed  Google Scholar 

  • Kay JE (1996) Structure-function relationships in the FK506-binding protein (FKBP) family of peptidylprolyl cis-trans isomerases. Biochem J 314:361–385

    CAS  PubMed Central  PubMed  Google Scholar 

  • Kazlauskas A, Poellinger L, Pongratz I (2000) The immunophilin-like protein XAP2 regulates ubiquitination and subcellular localization of the dioxin receptor. J Biol Chem 275(52):41317–41324

    CAS  PubMed  Google Scholar 

  • Kazlauskas A, Sundstrom S, Poellinger L, Pongratz I (2001) The hsp90 chaperone complex regulates intracellular localization of the dioxin receptor. Mol Cell Biol 21(7):2594–2607

    CAS  PubMed Central  PubMed  Google Scholar 

  • Kazlauskas A, Poellinger L, Pongratz I (2002) Two distinct regions of the immunophilin-like protein XAP2 regulate dioxin receptor function and interaction with hsp90. J Biol Chem 277(14):11795–11801

    CAS  PubMed  Google Scholar 

  • Kester HA, van der Leede BM, van der Saag PT, van der Burg B (1997) Novel progesterone target genes identified by an improved differential display technique suggest that progestin-induced growth inhibition of breast cancer cells coincides with enhancement of differentiation. J Biol Chem 272(26):16637–16643

    CAS  PubMed  Google Scholar 

  • Klengel T, Mehta D, Anacker C, Rex-Haffner M, Pruessner JC, Pariante CM, Pace TW, Mercer KB, Mayberg HS, Bradley B, Nemeroff CB, Holsboer F, Heim CM, Ressler KJ, Rein T, Binder EB (2013) Allele-specific FKBP5 DNA demethylation mediates gene-childhood trauma interactions. Nat Neurosci 16(1):33–41

    CAS  PubMed Central  PubMed  Google Scholar 

  • Komura E, Tonetti C, Penard-Lacronique V, Chagraoui H, Lacout C, Lecouedic JP, Rameau P, Debili N, Vainchenker W, Giraudier S (2005) Role for the nuclear factor kappaB pathway in transforming growth factor-beta1 production in idiopathic myelofibrosis: possible relationship with FK506 binding protein 51 overexpression. Cancer Res 65(8):3281–3289

    CAS  PubMed  Google Scholar 

  • Kong GK, Adams JJ, Cappai R, Parker MW (2007) Structure of Alzheimer’s disease amyloid precursor protein copper-binding domain at atomic resolution. Acta Crystallogr Sect F Struct Biol Cryst Commun 63(Pt 10):819–824. doi:10.1107/S1744309107041139

    CAS  PubMed Central  PubMed  Google Scholar 

  • Koren J 3rd, Jinwal UK, Davey Z, Kiray J, Arulselvam K, Dickey CA (2011) Bending tau into shape: the emerging role of peptidyl-prolyl isomerases in tauopathies. Mol Neurobiol 44(1):65–70. doi:10.1007/s12035-011-8182-4

    CAS  PubMed Central  PubMed  Google Scholar 

  • Kosano H, Stensgard B, Charlesworth MC, McMahon N, Toft D (1998) The assembly of progesterone receptor-hsp90 complexes using purified proteins. J Biol Chem 273(49):32973–32979

    CAS  PubMed  Google Scholar 

  • Krummrei U, Baulieu EE, Chambraud B (2003) The FKBP-associated protein FAP48 is an antiproliferative molecule and a player in T cell activation that increases IL2 synthesis. Proc Natl Acad Sci U S A 100(5):2444–2449

    CAS  PubMed Central  PubMed  Google Scholar 

  • Kumar P, Mark PJ, Ward BK, Minchin RF, Ratajczak T (2001) Estradiol-regulated expression of the immunophilins cyclophilin 40 and FKBP52 in MCF-7 breast cancer cells. Biochem Biophys Res Commun 284(1):219–225

    CAS  PubMed  Google Scholar 

  • Kurek I, Stoger E, Dulberger R, Christou P, Breiman A (2002) Overexpression of the wheat FK506-binding protein 73 (FKBP73) and the heat-induced wheat FKBP77 in transgenic wheat reveals different functions of the two isoforms. Transgenic Res 11(4):373–379

    CAS  PubMed  Google Scholar 

  • Kuzhandaivelu N, Cong YS, Inouye C, Yang WM, Seto E (1996) XAP2, a novel hepatitis B virus X-associated protein that inhibits X transactivation. Nucleic Acids Res 24(23):4741–4750

    CAS  PubMed Central  PubMed  Google Scholar 

  • Laenger A, Lang-Rollin I, Kozany C, Zschocke J, Zimmermann N, Ruegg J, Holsboer F, Hausch F, Rein T (2009) XAP2 inhibits glucocorticoid receptor activity in mammalian cells. FEBS Lett 583(9):1493–1498

    CAS  PubMed  Google Scholar 

  • Lahvis GP, Pyzalski RW, Glover E, Pitot HC, McElwee MK, Bradfield CA (2005) The aryl hydrocarbon receptor is required for developmental closure of the ductus venosus in the neonatal mouse. Mol Pharmacol 67(3):714–720

    CAS  PubMed  Google Scholar 

  • LaPres JJ, Glover E, Dunham EE, Bunger MK, Bradfield CA (2000) ARA9 modifies agonist signaling through an increase in cytosolic aryl hydrocarbon receptor. J Biol Chem 275(9):6153–6159

    CAS  PubMed  Google Scholar 

  • Lees MJ, Peet DJ, Whitelaw ML (2003) Defining the role for XAP2 in stabilization of the dioxin receptor. J Biol Chem 278(38):35878–35888

    CAS  PubMed  Google Scholar 

  • Lin TM, Ko K, Moore RW, Simanainen U, Oberley TD, Peterson RE (2002) Effects of aryl hydrocarbon receptor null mutation and in utero and lactational 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure on prostate and seminal vesicle development in C57BL/6 mice. Toxicol Sci 68(2):479–487

    CAS  PubMed  Google Scholar 

  • Liu G, Sanchez-Fernandez R, Li ZS, Rea PA (2001) Enhanced multispecificity of arabidopsis vacuolar multidrug resistance-associated protein-type ATP-binding cassette transporter, AtMRP2. J Biol Chem 276(12):8648–8656

    CAS  PubMed  Google Scholar 

  • Ma Q, Whitlock JP Jr (1997) A novel cytoplasmic protein that interacts with the Ah receptor, contains tetratricopeptide repeat motifs, and augments the transcriptional response to 2,3,7,8-tetrachlorodibenzo-p-dioxin. J Biol Chem 272(14):8878–8884

    CAS  PubMed  Google Scholar 

  • Madan AP, DeFranco DB (1993) Bidirectional transport of glucocorticoid receptors across the nuclear envelope. Proc Natl Acad Sci U S A 90(8):3588–3592

    CAS  PubMed Central  PubMed  Google Scholar 

  • Maestre-Martinez M, Edlich F, Jarczowski F, Weiwad M, Fischer G, Lucke C (2006) Solution structure of the FK506-binding domain of human FKBP38. J Biomol NMR 34(3):197–202

    CAS  PubMed  Google Scholar 

  • Maestre-Martinez M, Haupt K, Edlich F, Jahreis G, Jarczowski F, Erdmann F, Fischer G, Lucke C (2010) New structural aspects of FKBP38 activation. Biol Chem 391(10):1157–1167

    CAS  PubMed  Google Scholar 

  • Mamane Y, Sharma S, Petropoulos L, Lin R, Hiscott J (2000) Posttranslational regulation of IRF-4 activity by the immunophilin FKBP52. Immunity 12(2):129–140

    CAS  PubMed  Google Scholar 

  • Maruyama T, Suzuki R, Furutani M (2004) Archaeal peptidyl prolyl cis-trans isomerases (PPIases) update 2004. Front Biosci 9:1680–1720

    CAS  PubMed  Google Scholar 

  • McKeen HD, McAlpine K, Valentine A, Quinn DJ, McClelland K, Byrne C, O’Rourke M, Young S, Scott CJ, McCarthy HO, Hirst DG, Robson T (2008) A novel FK506-like binding protein interacts with the glucocorticoid receptor and regulates steroid receptor signaling. Endocrinology 149(11):5724–5734

    CAS  PubMed  Google Scholar 

  • McKeen HD, Byrne C, Jithesh PV, Donley C, Valentine A, Yakkundi A, O’Rourke M, Swanton C, McCarthy HO, Hirst DG, Robson T (2010) FKBPL regulates estrogen receptor signaling and determines response to endocrine therapy. Cancer Res 70(3):1090–1100

    CAS  PubMed  Google Scholar 

  • McKeen HD, Brennan DJ, Hegarty S, Lanigan F, Jirstrom K, Byrne C, Yakkundi A, McCarthy HO, Gallagher WM, Robson T (2011) The emerging role of FK506-binding proteins as cancer biomarkers: a focus on FKBPL. Biochem Soc Trans 39(2):663–668

    CAS  PubMed  Google Scholar 

  • Meng X, Lu X, Morris CA, Keating MT (1998) A novel human gene FKBP6 is deleted in Williams syndrome. Genomics 52(2):130–137

    CAS  PubMed  Google Scholar 

  • Meyer BK, Perdew GH (1999) Characterization of the AhR-hsp90-XAP2 core complex and the role of the immunophilin-related protein XAP2 in AhR stabilization. Biochemistry 38(28):8907–8917

    CAS  PubMed  Google Scholar 

  • Meyer BK, Pray-Grant MG, Vanden Heuvel JP, Perdew GH (1998) Hepatitis B virus X-associated protein 2 is a subunit of the unliganded aryl hydrocarbon receptor core complex and exhibits transcriptional enhancer activity. Mol Cell Biol 18(2):978–988

    CAS  PubMed Central  PubMed  Google Scholar 

  • Meyer BK, Petrulis JR, Perdew GH (2000) Aryl hydrocarbon (Ah) receptor levels are selectively modulated by hsp90-associated immunophilin homolog XAP2. Cell Stress Chaperones 5(3):243–254

    CAS  PubMed Central  PubMed  Google Scholar 

  • Miller CA (2002) Two tetratricopeptide repeat proteins facilitate human aryl hydrocarbon receptor signalling in yeast. Cell Signal 14(7):615–623

    CAS  PubMed  Google Scholar 

  • Mimura J, Fujii-Kuriyama Y (2003) Functional role of AhR in the expression of toxic effects by TCDD. Biochim Biophys Acta 1619(3):263–268

    CAS  PubMed  Google Scholar 

  • Miyata Y, Chambraud B, Radanyi C, Leclerc J, Lebeau MC, Renoir JM, Shirai R, Catelli MG, Yahara I, Baulieu EE (1997) Phosphorylation of the immunosuppressant FK506-binding protein FKBP52 by casein kinase II: regulation of HSP90-binding activity of FKBP52. Proc Natl Acad Sci U S A 94(26):14500–14505

    CAS  PubMed Central  PubMed  Google Scholar 

  • Mustafi SM, LeMaster DM, Hernandez G (2014) Differential conformational dynamics in the closely homologous FK506-binding domains of FKBP51 and FKBP52. Biochem J 461(1):115–123

    CAS  PubMed Central  PubMed  Google Scholar 

  • Nair SC, Rimerman RA, Toran EJ, Chen S, Prapapanich V, Butts RN, Smith DF (1997) Molecular cloning of human FKBP51 and comparisons of immunophilin interactions with Hsp90 and progesterone receptor. Mol Cell Biol 17(2):594–603

    CAS  PubMed Central  PubMed  Google Scholar 

  • Ni L, Yang CS, Gioeli D, Frierson H, Toft DO, Paschal BM (2010) FKBP51 promotes assembly of the Hsp90 chaperone complex and regulates androgen receptor signaling in prostate cancer cells. Mol Cell Biol 30(5):1243–1253

    CAS  PubMed Central  PubMed  Google Scholar 

  • Nukaya M, Lin BC, Glover E, Moran SM, Kennedy GD, Bradfield CA (2010) The aryl hydrocarbon receptor-interacting protein (AIP) is required for dioxin-induced hepatotoxicity but not for the induction of the Cyp1a1 and Cyp1a2 genes. J Biol Chem 285(46):35599–35605

    CAS  PubMed Central  PubMed  Google Scholar 

  • Okada M, Hatakeyama T, Itoh H, Tokuta N, Tokumitsu H, Kobayashi R (2004) S100A1 is a novel molecular chaperone and a member of the Hsp70/Hsp90 multichaperone complex. J Biol Chem 279(6):4221–4233. doi:10.1074/jbc.M309014200

    CAS  PubMed  Google Scholar 

  • O’Leary JC 3rd, Dharia S, Blair LJ, Brady S, Johnson AG, Peters M, Cheung-Flynn J, Cox MB, de Erausquin G, Weeber EJ, Jinwal UK, Dickey CA (2011) A new anti-depressive strategy for the elderly: ablation of FKBP5/FKBP51. PLoS One 6(9):e24840. doi:10.1371/journal.pone.0024840

    Google Scholar 

  • Ostrow KL, Park HL, Hoque MO, Kim MS, Liu J, Argani P, Westra W, Van Criekinge W, Sidransky D (2009) Pharmacologic unmasking of epigenetically silenced genes in breast cancer. Clin Cancer Res 15(4):1184–1191

    CAS  PubMed Central  PubMed  Google Scholar 

  • Pei H, Li L, Fridley BL, Jenkins GD, Kalari KR, Lingle W, Petersen G, Lou Z, Wang L (2009) FKBP51 affects cancer cell response to chemotherapy by negatively regulating Akt. Cancer Cell 16(3):259–266

    CAS  PubMed Central  PubMed  Google Scholar 

  • Perez-Perez JM, Ponce MR, Micol JL (2004) The ULTRACURVATA2 gene of Arabidopsis encodes an FK506-binding protein involved in auxin and brassinosteroid signaling. Plant Physiol 134(1):101–117

    CAS  PubMed Central  PubMed  Google Scholar 

  • Petrulis JR, Perdew GH (2002) The role of chaperone proteins in the aryl hydrocarbon receptor core complex. Chem Biol Interact 141(1–2):25–40

    CAS  PubMed  Google Scholar 

  • Petrulis JR, Hord NG, Perdew GH (2000) Subcellular localization of the aryl hydrocarbon receptor is modulated by the immunophilin homolog hepatitis B virus X-associated protein 2. J Biol Chem 275(48):37448–37453

    CAS  PubMed  Google Scholar 

  • Petrulis JR, Kusnadi A, Ramadoss P, Hollingshead B, Perdew GH (2003) The hsp90 Co-chaperone XAP2 alters importin beta recognition of the bipartite nuclear localization signal of the Ah receptor and represses transcriptional activity. J Biol Chem 278(4):2677–2685

    CAS  PubMed  Google Scholar 

  • Pirkl F, Buchner J (2001) Functional analysis of the Hsp90-associated human peptidyl prolyl cis/trans isomerases FKBP51, FKBP52 and Cyp40. J Mol Biol 308(4):795–806

    CAS  PubMed  Google Scholar 

  • Pirkl F, Fischer E, Modrow S, Buchner J (2001) Localization of the chaperone domain of FKBP52. J Biol Chem 276(40):37034–37041

    CAS  PubMed  Google Scholar 

  • Presman DM, Alvarez LD, Levi V, Eduardo S, Digman MA, Marti MA, Veleiro AS, Burton G, Pecci A (2010) Insights on glucocorticoid receptor activity modulation through the binding of rigid steroids. PLoS One 5(10):e13279

    PubMed Central  PubMed  Google Scholar 

  • Presman DM, Ogara MF, Stortz M, Alvarez LD, Pooley JR, Schiltz RL, Grontved L, Johnson TA, Mittelstadt PR, Ashwell JD, Ganesan S, Burton G, Levi V, Hager GL, Pecci A (2014) Live cell imaging unveils multiple domain requirements for in vivo dimerization of the glucocorticoid receptor. PLoS Biol 12(3):e1001813

    PubMed Central  PubMed  Google Scholar 

  • Qing K, Hansen J, Weigel-Kelley KA, Tan M, Zhou S, Srivastava A (2001) Adeno-associated virus type 2-mediated gene transfer: role of cellular FKBP52 protein in transgene expression. J Virol 75(19):8968–8976

    CAS  PubMed Central  PubMed  Google Scholar 

  • Quintá HR, Maschi D, Gomez-Sanchez C, Piwien Pilipuk G, Galigniana MD (2010) Subcellular rearrangement of hsp90-binding immunophilins accompanies neuronal differentiation and neurite outgrowth. J Neurochem 115:716–734

    PubMed Central  PubMed  Google Scholar 

  • Reynolds PD, Ruan Y, Smith DF, Scammell JG (1999) Glucocorticoid resistance in the squirrel monkey is associated with overexpression of the immunophilin FKBP51. J Clin Endocrinol Metab 84(2):663–669

    CAS  PubMed  Google Scholar 

  • Riggs DL, Roberts PJ, Chirillo SC, Cheung-Flynn J, Prapapanich V, Ratajczak T, Gaber R, Picard D, Smith DF (2003) The Hsp90-binding peptidylprolyl isomerase FKBP52 potentiates glucocorticoid signaling in vivo. EMBO J 22(5):1158–1167

    CAS  PubMed Central  PubMed  Google Scholar 

  • Riggs DL, Cox MB, Cheung-Flynn J, Prapapanich V, Carrigan PE, Smith DF (2004) Functional specificity of co-chaperone interactions with Hsp90 client proteins. Crit Rev Biochem Mol Biol 39:279–295

    CAS  PubMed  Google Scholar 

  • Riggs DL, Cox MB, Tardif HL, Hessling M, Buchner J, Smith DF (2007) Noncatalytic role of the FKBP52 peptidyl-prolyl isomerase domain in the regulation of steroid hormone signaling. Mol Cell Biol 27(24):8658–8669

    CAS  PubMed Central  PubMed  Google Scholar 

  • Robson T, James IF (2012) The therapeutic and diagnostic potential of FKBPL; a novel anticancer protein. Drug Discov Today 17(11–12):544–548

    CAS  PubMed  Google Scholar 

  • Robson TA, Lohrer H, Bailie JR, Hirst DG, Joiner MC, Arrand JE (1997) Gene regulation by low-dose ionizing radiation in a normal human lung epithelial cell line. Biochem Soc Trans 25(1):335–342

    CAS  PubMed  Google Scholar 

  • Robson T, Joiner MC, Wilson GD, McCullough W, Price ME, Logan I, Jones H, McKeown SR, Hirst DG (1999) A novel human stress response-related gene with a potential role in induced radioresistance. Radiat Res 152(5):451–461

    CAS  PubMed  Google Scholar 

  • Robson T, Price ME, Moore ML, Joiner MC, McKelvey-Martin VJ, McKeown SR, Hirst DG (2000) Increased repair and cell survival in cells treated with DIR1 antisense oligonucleotides: implications for induced radioresistance. Int J Radiat Biol 76(5):617–623

    CAS  PubMed  Google Scholar 

  • Romano P, Gray J, Horton P, Luan S (2005) Plant immunophilins: functional versatility beyond protein maturation. New Phytol 166(3):753–769

    Google Scholar 

  • Romano S, D’Angelillo A, Pacelli R, Staibano S, De LE, Bisogni R, Eskelinen EL, Mascolo M, Cali G, Arra C, Romano MF (2010) Role of FK506-binding protein 51 in the control of apoptosis of irradiated melanoma cells. Cell Death Differ 17(1):145–157

    CAS  PubMed  Google Scholar 

  • Rosner M, Hofer K, Kubista M, Hengstschlager M (2003) Cell size regulation by the human TSC tumor suppressor proteins depends on PI3K and FKBP38. Oncogene 22(31):4786–4798

    CAS  PubMed  Google Scholar 

  • Rouviere N, Vincent M, Craescu CT, Gallay J (1997) Immunosuppressor binding to the immunophilin FKBP59 affects the local structural dynamics of a surface beta-strand: time-resolved fluorescence study. Biochemistry 36(24):7339–7352

    CAS  PubMed  Google Scholar 

  • Sanchez ER (1990) Hsp56: a novel heat shock protein associated with untransformed steroid receptor complexes. J Biol Chem 265(36):22067–22070

    CAS  PubMed  Google Scholar 

  • Sanokawa-Akakura R, Dai H, Akakura S, Weinstein D, Fajardo JE, Lang SE, Wadsworth S, Siekierka J, Birge RB (2004) A novel role for the immunophilin FKBP52 in copper transport. J Biol Chem 279(27):27845–27848

    CAS  PubMed  Google Scholar 

  • Sanokawa-Akakura R, Cao W, Allan K, Patel K, Ganesh A, Heiman G, Burke R, Kemp FW, Bogden JD, Camakaris J, Birge RB, Konsolaki M (2010) Control of Alzheimer’s amyloid beta toxicity by the high molecular weight immunophilin FKBP52 and copper homeostasis in Drosophila. PLoS One 5(1):e8626. doi:10.1371/journal.pone.0008626

    PubMed Central  PubMed  Google Scholar 

  • Santamaria-Kisiel L, Rintala-Dempsey AC, Shaw GS (2006) Calcium-dependent and -independent interactions of the S100 protein family. Biochem J 396(2):201–214. doi:10.1042/BJ20060195

    CAS  PubMed Central  PubMed  Google Scholar 

  • Scheufler C, Brinker A, Bourenkov G, Pegoraro S, Moroder L, Bartunik H, Hartl FU, Moarefi I (2000) Structure of TPR domain-peptide complexes: critical elements in the assembly of the Hsp70-Hsp90 multichaperone machine. Cell 101(2):199–210

    CAS  PubMed  Google Scholar 

  • Schulke JP, Wochnik GM, Lang-Rollin I, Gassen NC, Knapp RT, Berning B, Yassouridis A, Rein T (2010) Differential impact of tetratricopeptide repeat proteins on the steroid hormone receptors. PLoS One 5(7):e11717. doi:10.1371/journal.pone.0011717

    PubMed Central  PubMed  Google Scholar 

  • Shimamoto S, Kubota Y, Tokumitsu H, Kobayashi R (2010) S100 proteins regulate the interaction of Hsp90 with Cyclophilin 40 and FKBP52 through their tetratricopeptide repeats. FEBS Lett 584(6):1119–1125

    CAS  PubMed  Google Scholar 

  • Shirane M, Nakayama KI (2004) Immunophilin FKBP38, an inherent inhibitor of calcineurin, targets Bcl-2 to mitochondria and inhibits apoptosis. Nippon Rinsho 62(2):405–412

    PubMed  Google Scholar 

  • Silverstein AM, Galigniana MD, Chen MS, Owens-Grillo JK, Chinkers M, Pratt WB (1997) Protein phosphatase 5 is a major component of glucocorticoid receptor hsp90 complexes with properties of an FK506-binding immunophilin. J Biol Chem 272(26):16224–16230

    CAS  PubMed  Google Scholar 

  • Silverstein AM, Galigniana MD, Kanelakis KC, Radanyi C, Renoir JM, Pratt WB (1999) Different regions of the immunophilin FKBP52 determine its association with the glucocorticoid receptor, hsp90, and cytoplasmic dynein. J Biol Chem 274(52):36980–36986 [In Process Citation]

    CAS  PubMed  Google Scholar 

  • Sinars CR, Cheung-Flynn J, Rimerman RA, Scammell JG, Smith DF, Clardy J (2003) Structure of the large FK506-binding protein FKBP51, an Hsp90-binding protein and a component of steroid receptor complexes. Proc Natl Acad Sci U S A 100(3):868–873

    CAS  PubMed Central  PubMed  Google Scholar 

  • Sinkins WG, Goel M, Estacion M, Schilling WP (2004) Association of immunophilins with mammalian TRPC channels. J Biol Chem 279(33):34521–34529

    CAS  PubMed  Google Scholar 

  • Sivils JC, Storer CL, Galigniana MD, Cox MB (2011) Regulation of steroid hormone receptor function by the 52-kDa FK506-binding protein (FKBP52). Curr Opin Pharmacol 19:19

    Google Scholar 

  • Smith DF, Faber LE, Toft DO (1990) Purification of unactivated progesterone receptor and identification of novel receptor-associated proteins. J Biol Chem 265(7):3996–4003

    CAS  PubMed  Google Scholar 

  • Smith DF, Albers MW, Schreiber SL, Leach KL, Deibel MR Jr (1993a) FKBP54, a novel FK506-binding protein in avian progesterone receptor complexes and HeLa extracts. J Biol Chem 268(32):24270–24273

    CAS  Google Scholar 

  • Smith DF, Baggenstoss BA, Marion TN, Rimerman RA (1993b) Two FKBP-related proteins are associated with progesterone receptor complexes. J Biol Chem 268(24):18365–18371

    CAS  Google Scholar 

  • Solassol J, Mange A, Maudelonde T (2011) FKBP family proteins as promising new biomarkers for cancer. Curr Opin Pharmacol 11(4):320–325

    CAS  PubMed  Google Scholar 

  • Sumanasekera WK, Tien ES, Turpey R, Vanden Heuvel JP, Perdew GH (2003) Evidence that peroxisome proliferator-activated receptor alpha is complexed with the 90-kDa heat shock protein and the hepatitis virus B X-associated protein 2. J Biol Chem 278(7):4467–4473

    CAS  PubMed  Google Scholar 

  • Sunnotel O, Hiripi L, Lagan K, McDaid JR, De Leon JM, Miyagawa Y, Crowe H, Kaluskar S, Ward M, Scullion C, Campbell A, Downes CS, Hirst D, Barton D, Mocanu E, Tsujimura A, Cox MB, Robson T, Walsh CP (2010) Alterations in the steroid hormone receptor co-chaperone FKBPL are associated with male infertility: a case-control study. Reprod Biol Endocrinol 8(22):22

    PubMed Central  PubMed  Google Scholar 

  • Tatro ET, Everall IP, Kaul M, Achim CL (2009) Modulation of glucocorticoid receptor nuclear translocation in neurons by immunophilins FKBP51 and FKBP52: implications for major depressive disorder. Brain Res 1286:1–12

    CAS  PubMed Central  PubMed  Google Scholar 

  • Thackaberry EA, Bedrick EJ, Goens MB, Danielson L, Lund AK, Gabaldon D, Smith SM, Walker MK (2003) Insulin regulation in AhR-null mice: embryonic cardiac enlargement, neonatal macrosomia, and altered insulin regulation and response in pregnant and aging AhR-null females. Toxicol Sci 76(2):407–417

    CAS  PubMed  Google Scholar 

  • Thomas M, Harrell JM, Morishima Y, Peng HM, Pratt WB, Lieberman AP (2006) Pharmacologic and genetic inhibition of hsp90-dependent trafficking reduces aggregation and promotes degradation of the expanded glutamine androgen receptor without stress protein induction. Hum Mol Genet 15(11):1876–1883

    CAS  PubMed  Google Scholar 

  • Touma C, Gassen NC, Herrmann L, Cheung-Flynn J, Bull DR, Ionescu IA, Heinzmann JM, Knapman A, Siebertz A, Depping AM, Hartmann J, Hausch F, Schmidt MV, Holsboer F, Ising M, Cox MB, Schmidt U, Rein T (2011) FK506 binding protein 5 shapes stress responsiveness: modulation of neuroendocrine reactivity and coping behavior. Biol Psychiatry 70(10):928–936. doi:10.1016/j.biopsych.2011.07.023

    CAS  PubMed  Google Scholar 

  • Tranguch S, Cheung-Flynn J, Daikoku T, Prapapanich V, Cox MB, Xie H, Wang H, Das SK, Smith DF, Dey SK (2005) Cochaperone immunophilin FKBP52 is critical to uterine receptivity for embryo implantation. Proc Natl Acad Sci U S A 102(40):14326–14331

    CAS  PubMed Central  PubMed  Google Scholar 

  • Trivellin G, Korbonits M (2011) AIP and its interacting partners. J Endocrinol 210(2):137–155

    CAS  PubMed  Google Scholar 

  • Vafopoulou X, Steel CG (2012) Cytoplasmic travels of the ecdysteroid receptor in target cells: pathways for both genomic and non-genomic actions. Front Endocrinol (Lausanne) 3(43):43

    Google Scholar 

  • Valentine A, O’Rourke M, Yakkundi A, Worthington J, Hookham M, Bicknell R, McCarthy HO, McClelland K, McCallum L, Dyer H, McKeen H, Waugh DJ, Roberts J, McGregor J, Cotton G, James I, Harrison T, Hirst DG, Robson T (2011) FKBPL and peptide derivatives: novel biological agents that inhibit angiogenesis by a CD44-dependent mechanism. Clin Cancer Res 17(5):1044–1056

    CAS  PubMed Central  PubMed  Google Scholar 

  • Vermeer H, Hendriks-Stegeman BI, van der Burg B, van Buul-Offers SC, Jansen M (2003) Glucocorticoid-induced increase in lymphocytic FKBP51 messenger ribonucleic acid expression: a potential marker for glucocorticoid sensitivity, potency, and bioavailability. J Clin Endocrinol Metab 88(1):277–284

    CAS  PubMed  Google Scholar 

  • Vittorioso P, Cowling R, Faure JD, Caboche M, Bellini C (1998) Mutation in the Arabidopsis PASTICCINO1 gene, which encodes a new FK506- binding protein-like protein, has a dramatic effect on plant development. Mol Cell Biol 18(5):3034–3043

    CAS  PubMed Central  PubMed  Google Scholar 

  • Wadekar SA, Li D, Sanchez ER (2004) Agonist-activated glucocorticoid receptor inhibits binding of heat shock factor 1 to the heat shock protein 70 promoter in vivo. Mol Endocrinol 18(3):500–508

    CAS  PubMed  Google Scholar 

  • Wang J, Tong W, Zhang X, Chen L, Yi Z, Pan T, Hu Y, Xiang L, Yuan Z (2006) Hepatitis C virus non-structural protein NS5A interacts with FKBP38 and inhibits apoptosis in Huh7 hepatoma cells. FEBS Lett 580(18):4392–4400

    CAS  PubMed  Google Scholar 

  • Ward BK, Mark PJ, Ingram DM, Minchin RF, Ratajczak T (1999) Expression of the estrogen receptor-associated immunophilins, cyclophilin 40 and FKBP52, in breast cancer. Breast Cancer Res Treat 58(3):267–280

    CAS  PubMed  Google Scholar 

  • Warrier M, Hinds TD Jr, Ledford KJ, Cash HA, Patel PR, Bowman TA, Stechschulte LA, Yong W, Shou W, Najjar SM, Sanchez ER (2010) Susceptibility to diet-induced hepatic steatosis and glucocorticoid resistance in FK506-binding protein 52-deficient mice. Endocrinology 151(7):3225–3236

    CAS  PubMed Central  PubMed  Google Scholar 

  • Wenger RH, Stiehl DP, Camenisch G (2005) Integration of oxygen signaling at the consensus HRE. Sci STKE 2005(306):re12

    Google Scholar 

  • Wochnik GM, Ruegg J, Abel GA, Schmidt U, Holsboer F, Rein T (2005) FK506-binding proteins 51 and 52 differentially regulate dynein interaction and nuclear translocation of the glucocorticoid receptor in mammalian cells. J Biol Chem 280(6):4609–4616

    CAS  PubMed  Google Scholar 

  • Wong RL, Wlodarczyk BJ, Min KS, Scott ML, Kartiko S, Yu W, Merriweather MY, Vogel P, Zambrowicz BP, Finnell RH (2008) Mouse Fkbp8 activity is required to inhibit cell death and establish dorso-ventral patterning in the posterior neural tube. Hum Mol Genet 17(4):587–601

    CAS  PubMed  Google Scholar 

  • Wright NT, Cannon BR, Zimmer DB, Weber DJ (2009) S100A1: structure, function, and therapeutic potential. Curr Chem Biol 3(2):138–145

    CAS  PubMed Central  PubMed  Google Scholar 

  • Wu B, Li P, Liu Y, Lou Z, Ding Y, Shu C, Ye S, Bartlam M, Shen B, Rao Z (2004) 3D structure of human FK506-binding protein 52: implications for the assembly of the glucocorticoid receptor/Hsp90/immunophilin heterocomplex. Proc Natl Acad Sci U S A 101(22):8348–8353

    CAS  PubMed Central  PubMed  Google Scholar 

  • Yakkundi A, McCallum L, O’Kane A, Dyer H, Worthington J, McKeen HD, McClements L, Elliott C, McCarthy HO, Hirst DG, Robson T (2013) The anti-migratory effects of FKBPL and its peptide derivative, AD-01: regulation of CD44 and the cytoskeletal pathway. PLoS One 8(2):e55075

    CAS  PubMed Central  PubMed  Google Scholar 

  • Yang Q, Guan KL (2007) Expanding mTOR signaling. Cell Res 17(8):666–681

    CAS  PubMed  Google Scholar 

  • Yong W, Yang Z, Periyasamy S, Chen H, Yucel S, Li W, Lin LY, Wolf IM, Cohn MJ, Baskin LS, Sanchez ER, Shou W (2007) Essential role for co-chaperone Fkbp52 but not Fkbp51 in androgen receptor-mediated signaling and physiology. J Biol Chem 282(7):5026–5036

    CAS  PubMed Central  PubMed  Google Scholar 

  • Yoshida NL, Miyashita T, U M, Yamada M, Reed JC, Sugita Y, Oshida T (2002) Analysis of gene expression patterns during glucocorticoid-induced apoptosis using oligonucleotide arrays. Biochem Biophys Res Commun 293(4):1254–1261

    PubMed  Google Scholar 

  • Zaffran S (2000) Molecular cloning and embryonic expression of dFKBP59, a novel Drosophila FK506-binding protein. Gene 246(1–2):103–109

    CAS  PubMed  Google Scholar 

  • Zhang X, Clark AF, Yorio T (2008) FK506-binding protein 51 regulates nuclear transport of the glucocorticoid receptor beta and glucocorticoid responsiveness. Invest Ophthalmol Vis Sci 49(3):1037–1047. doi:10.1167/iovs.07-1279

    PubMed Central  PubMed  Google Scholar 

  • Zhao W, Zhong L, Wu J, Chen L, Qing K, Weigel-Kelley KA, Larsen SH, Shou W, Warrington KH Jr, Srivastava A (2006) Role of cellular FKBP52 protein in intracellular trafficking of recombinant adeno-associated virus 2 vectors. Virology 353(2):283–293

    CAS  PubMed Central  PubMed  Google Scholar 

  • Zhong L, Qing K, Si Y, Chen L, Tan M, Srivastava A (2004) Heat-shock treatment-mediated increase in transduction by recombinant adeno-associated virus 2 vectors is independent of the cellular heat-shock protein 90. J Biol Chem 279(13):12714–12723

    CAS  PubMed Central  PubMed  Google Scholar 

  • Zhu W, Zhang JS, Young CY (2001) Silymarin inhibits function of the androgen receptor by reducing nuclear localization of the receptor in the human prostate cancer cell line LNCaP. Carcinogenesis 22(9):1399–1403

    CAS  PubMed  Google Scholar 

  • Zimmer DB, Chaplin J, Baldwin A, Rast M (2005) S100-mediated signal transduction in the nervous system and neurological diseases. Cell Mol Biol (Noisy-le-grand) 51(2):201–214

    CAS  Google Scholar 

Download references

Acknowledgements

Studies in the authors’ laboratory were supported by grants to the Border Biomedical Research Center from the National Center for Research Resources (5 G12 RR008124) and from the National Institute on Minority Health and Health Disparities (8 G12 MD007592) from the National Institutes of Health. The authors were also supported in part by the Cancer Prevention and Research Institute of Texas by grant number RP110444-P2 (M.B.C). M.D.G. was supported by grants PICT 2011-1715, UBACYT 2011-14-GC, and the Fundación Roemmers. The text in this chapter contains sections reproduced with kind permission from Springer Science + Business Media: Networking of Chaperones by Co-chaperones; Chapter 2: Functions of the Hsp90-Binding FKBP Immunophilins; 2006; page 13–21; Marc B. Cox and David F. Smith

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Marc B. Cox .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and Permissions

Copyright information

© 2015 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Guy, N., Garcia, Y., Sivils, J., Galigniana, M., Cox, M. (2015). Functions of the Hsp90-Binding FKBP Immunophilins. In: Blatch, G., Edkins, A. (eds) The Networking of Chaperones by Co-chaperones. Subcellular Biochemistry, vol 78. Springer, Cham. https://doi.org/10.1007/978-3-319-11731-7_2

Download citation