Search tips
Search criteria 


Logo of molcellbPermissionsJournals.ASM.orgJournalMCB ArticleJournal InfoAuthorsReviewers
Mol Cell Biol. 1997 February; 17(2): 594–603.
PMCID: PMC231784

Molecular cloning of human FKBP51 and comparisons of immunophilin interactions with Hsp90 and progesterone receptor.


A cDNA for human FKBP51 has been cloned and sequenced, and protein products have been expressed in both in vitro and bacterial systems. The deduced amino acid sequence for human FKBP51 is 90% identical to sequences of recently described murine proteins and is 55% identical to the sequence of human FKBP52. Human FKBP51 mRNA is expressed in a wide range of tissues, and the protein has peptidylprolyl isomerase activity that is inhibited by FK506 but not cyclosporine. FKBP51 is the same as a previously described progesterone receptor-associated immunophilin that, similar to FKBP52 and cyclophilin 40, is an Hsp90-binding protein and appears in functionally mature steroid receptor complexes along with Hsp90 and p23. Each of the three receptor-associated immunophilins displays interactions with progesterone receptor that are more dynamic than Hsp90-receptor interactions. Whereas FKBP52 and FKBP51 compete about equally well for binding to Hsp90 in a purified system, FKBP51 accumulates preferentially in progesterone receptor complexes assembled in a cell-free system. This observation provides a precedent for differential interactions between Hsp90-associated immunophilins and target proteins such as steroid receptors.

Full Text

The Full Text of this article is available as a PDF (563K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Baughman G, Wiederrecht GJ, Campbell NF, Martin MM, Bourgeois S. FKBP51, a novel T-cell-specific immunophilin capable of calcineurin inhibition. Mol Cell Biol. 1995 Aug;15(8):4395–4402. [PMC free article] [PubMed]
  • Brugge JS. Interaction of the Rous sarcoma virus protein pp60src with the cellular proteins pp50 and pp90. Curr Top Microbiol Immunol. 1986;123:1–22. [PubMed]
  • Chen S, Prapapanich V, Rimerman RA, Honoré B, Smith DF. Interactions of p60, a mediator of progesterone receptor assembly, with heat shock proteins hsp90 and hsp70. Mol Endocrinol. 1996 Jun;10(6):682–693. [PubMed]
  • Czar MJ, Owens-Grillo JK, Dittmar KD, Hutchison KA, Zacharek AM, Leach KL, Deibel MR, Jr, Pratt WB. Characterization of the protein-protein interactions determining the heat shock protein (hsp90.hsp70.hsp56) heterocomplex. J Biol Chem. 1994 Apr 15;269(15):11155–11161. [PubMed]
  • Goebl M, Yanagida M. The TPR snap helix: a novel protein repeat motif from mitosis to transcription. Trends Biochem Sci. 1991 May;16(5):173–177. [PubMed]
  • Höhfeld J, Minami Y, Hartl FU. Hip, a novel cochaperone involved in the eukaryotic Hsc70/Hsp40 reaction cycle. Cell. 1995 Nov 17;83(4):589–598. [PubMed]
  • Honoré B, Leffers H, Madsen P, Rasmussen HH, Vandekerckhove J, Celis JE. Molecular cloning and expression of a transformation-sensitive human protein containing the TPR motif and sharing identity to the stress-inducible yeast protein STI1. J Biol Chem. 1992 Apr 25;267(12):8485–8491. [PubMed]
  • Hutchison KA, Brott BK, De Leon JH, Perdew GH, Jove R, Pratt WB. Reconstitution of the multiprotein complex of pp60src, hsp90, and p50 in a cell-free system. J Biol Chem. 1992 Feb 15;267(5):2902–2908. [PubMed]
  • Johnson JL, Beito TG, Krco CJ, Toft DO. Characterization of a novel 23-kilodalton protein of unactive progesterone receptor complexes. Mol Cell Biol. 1994 Mar;14(3):1956–1963. [PMC free article] [PubMed]
  • Johnson J, Corbisier R, Stensgard B, Toft D. The involvement of p23, hsp90, and immunophilins in the assembly of progesterone receptor complexes. J Steroid Biochem Mol Biol. 1996 Jan;56(1-6):31–37. [PubMed]
  • Johnson JL, Toft DO. A novel chaperone complex for steroid receptors involving heat shock proteins, immunophilins, and p23. J Biol Chem. 1994 Oct 7;269(40):24989–24993. [PubMed]
  • Johnson JL, Toft DO. Binding of p23 and hsp90 during assembly with the progesterone receptor. Mol Endocrinol. 1995 Jun;9(6):670–678. [PubMed]
  • Kay JE. Structure-function relationships in the FK506-binding protein (FKBP) family of peptidylprolyl cis-trans isomerases. Biochem J. 1996 Mar 1;314(Pt 2):361–385. [PubMed]
  • Kieffer LJ, Seng TW, Li W, Osterman DG, Handschumacher RE, Bayney RM. Cyclophilin-40, a protein with homology to the P59 component of the steroid receptor complex. Cloning of the cDNA and further characterization. J Biol Chem. 1993 Jun 15;268(17):12303–12310. [PubMed]
  • Kralli A, Yamamoto KR. An FK506-sensitive transporter selectively decreases intracellular levels and potency of steroid hormones. J Biol Chem. 1996 Jul 19;271(29):17152–17156. [PubMed]
  • Lebeau MC, Massol N, Herrick J, Faber LE, Renoir JM, Radanyi C, Baulieu EE. P59, an hsp 90-binding protein. Cloning and sequencing of its cDNA and preparation of a peptide-directed polyclonal antibody. J Biol Chem. 1992 Mar 5;267(7):4281–4284. [PubMed]
  • Massol N, Lebeau MC, Renoir JM, Faber LE, Baulieu EE. Rabbit FKBP59-heat shock protein binding immunophillin (HBI) is a calmodulin binding protein. Biochem Biophys Res Commun. 1992 Sep 30;187(3):1330–1335. [PubMed]
  • Owens-Grillo JK, Hoffmann K, Hutchison KA, Yem AW, Deibel MR, Jr, Handschumacher RE, Pratt WB. The cyclosporin A-binding immunophilin CyP-40 and the FK506-binding immunophilin hsp56 bind to a common site on hsp90 and exist in independent cytosolic heterocomplexes with the untransformed glucocorticoid receptor. J Biol Chem. 1995 Sep 1;270(35):20479–20484. [PubMed]
  • Peattie DA, Harding MW, Fleming MA, DeCenzo MT, Lippke JA, Livingston DJ, Benasutti M. Expression and characterization of human FKBP52, an immunophilin that associates with the 90-kDa heat shock protein and is a component of steroid receptor complexes. Proc Natl Acad Sci U S A. 1992 Nov 15;89(22):10974–10978. [PubMed]
  • Prapapanich V, Chen S, Nair SC, Rimerman RA, Smith DF. Molecular cloning of human p48, a transient component of progesterone receptor complexes and an Hsp70-binding protein. Mol Endocrinol. 1996 Apr;10(4):420–431. [PubMed]
  • Prapapanich V, Chen S, Toran EJ, Rimerman RA, Smith DF. Mutational analysis of the hsp70-interacting protein Hip. Mol Cell Biol. 1996 Nov;16(11):6200–6207. [PMC free article] [PubMed]
  • Pratt WB, Czar MJ, Stancato LF, Owens JK. The hsp56 immunophilin component of steroid receptor heterocomplexes: could this be the elusive nuclear localization signal-binding protein? J Steroid Biochem Mol Biol. 1993 Sep;46(3):269–279. [PubMed]
  • Radanyi C, Chambraud B, Baulieu EE. The ability of the immunophilin FKBP59-HBI to interact with the 90-kDa heat shock protein is encoded by its tetratricopeptide repeat domain. Proc Natl Acad Sci U S A. 1994 Nov 8;91(23):11197–11201. [PubMed]
  • Ratajczak T, Carrello A. Cyclophilin 40 (CyP-40), mapping of its hsp90 binding domain and evidence that FKBP52 competes with CyP-40 for hsp90 binding. J Biol Chem. 1996 Feb 9;271(6):2961–2965. [PubMed]
  • Ratajczak T, Carrello A, Mark PJ, Warner BJ, Simpson RJ, Moritz RL, House AK. The cyclophilin component of the unactivated estrogen receptor contains a tetratricopeptide repeat domain and shares identity with p59 (FKBP59). J Biol Chem. 1993 Jun 25;268(18):13187–13192. [PubMed]
  • Renoir JM, Radanyi C, Faber LE, Baulieu EE. The non-DNA-binding heterooligomeric form of mammalian steroid hormone receptors contains a hsp90-bound 59-kilodalton protein. J Biol Chem. 1990 Jun 25;265(18):10740–10745. [PubMed]
  • Ruff VA, Yem AW, Munns PL, Adams LD, Reardon IM, Deibel MR, Jr, Leach KL. Tissue distribution and cellular localization of hsp56, an FK506-binding protein. Characterization using a highly specific polyclonal antibody. J Biol Chem. 1992 Oct 25;267(30):21285–21288. [PubMed]
  • Sanchez ER. Hsp56: a novel heat shock protein associated with untransformed steroid receptor complexes. J Biol Chem. 1990 Dec 25;265(36):22067–22070. [PubMed]
  • Sanchez ER, Faber LE, Henzel WJ, Pratt WB. The 56-59-kilodalton protein identified in untransformed steroid receptor complexes is a unique protein that exists in cytosol in a complex with both the 70- and 90-kilodalton heat shock proteins. Biochemistry. 1990 May 29;29(21):5145–5152. [PubMed]
  • Schneider C, Newman RA, Sutherland DR, Asser U, Greaves MF. A one-step purification of membrane proteins using a high efficiency immunomatrix. J Biol Chem. 1982 Sep 25;257(18):10766–10769. [PubMed]
  • Smith DF. Dynamics of heat shock protein 90-progesterone receptor binding and the disactivation loop model for steroid receptor complexes. Mol Endocrinol. 1993 Nov;7(11):1418–1429. [PubMed]
  • Smith DF, Albers MW, Schreiber SL, Leach KL, Deibel MR., Jr FKBP54, a novel FK506-binding protein in avian progesterone receptor complexes and HeLa extracts. J Biol Chem. 1993 Nov 15;268(32):24270–24273. [PubMed]
  • Smith DF, Baggenstoss BA, Marion TN, Rimerman RA. Two FKBP-related proteins are associated with progesterone receptor complexes. J Biol Chem. 1993 Aug 25;268(24):18365–18371. [PubMed]
  • Smith DF, Faber LE, Toft DO. Purification of unactivated progesterone receptor and identification of novel receptor-associated proteins. J Biol Chem. 1990 Mar 5;265(7):3996–4003. [PubMed]
  • Smith DF, Sullivan WP, Marion TN, Zaitsu K, Madden B, McCormick DJ, Toft DO. Identification of a 60-kilodalton stress-related protein, p60, which interacts with hsp90 and hsp70. Mol Cell Biol. 1993 Feb;13(2):869–876. [PMC free article] [PubMed]
  • Smith DF, Whitesell L, Nair SC, Chen S, Prapapanich V, Rimerman RA. Progesterone receptor structure and function altered by geldanamycin, an hsp90-binding agent. Mol Cell Biol. 1995 Dec;15(12):6804–6812. [PMC free article] [PubMed]
  • Stancato LF, Chow YH, Hutchison KA, Perdew GH, Jove R, Pratt WB. Raf exists in a native heterocomplex with hsp90 and p50 that can be reconstituted in a cell-free system. J Biol Chem. 1993 Oct 15;268(29):21711–21716. [PubMed]
  • Tai PK, Albers MW, Chang H, Faber LE, Schreiber SL. Association of a 59-kilodalton immunophilin with the glucocorticoid receptor complex. Science. 1992 May 29;256(5061):1315–1318. [PubMed]
  • Tai PK, Maeda Y, Nakao K, Wakim NG, Duhring JL, Faber LE. A 59-kilodalton protein associated with progestin, estrogen, androgen, and glucocorticoid receptors. Biochemistry. 1986 Sep 9;25(18):5269–5275. [PubMed]
  • Whitesell L, Mimnaugh EG, De Costa B, Myers CE, Neckers LM. Inhibition of heat shock protein HSP90-pp60v-src heteroprotein complex formation by benzoquinone ansamycins: essential role for stress proteins in oncogenic transformation. Proc Natl Acad Sci U S A. 1994 Aug 30;91(18):8324–8328. [PubMed]
  • Yeh WC, Li TK, Bierer BE, McKnight SL. Identification and characterization of an immunophilin expressed during the clonal expansion phase of adipocyte differentiation. Proc Natl Acad Sci U S A. 1995 Nov 21;92(24):11081–11085. [PubMed]
  • Yem AW, Tomasselli AG, Heinrikson RL, Zurcher-Neely H, Ruff VA, Johnson RA, Deibel MR., Jr The Hsp56 component of steroid receptor complexes binds to immobilized FK506 and shows homology to FKBP-12 and FKBP-13. J Biol Chem. 1992 Feb 15;267(5):2868–2871. [PubMed]

Articles from Molecular and Cellular Biology are provided here courtesy of American Society for Microbiology (ASM)