FKBP51 and FKBP52 in signaling and disease

FKBP51 and FKBP52 are diverse regulators of steroid hormone receptor signaling, including receptor maturation, hormone binding and nuclear translocation. Although structurally similar, they are functionally divergent, which is largely attributed to differences in the FK1 domain and the proline-rich...

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Autor principal: Storer, C.L
Otros Autores: Dickey, C.A, Galigniana, M.D, Rein, T., Cox, M.B
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Publicado: 2011
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024 7 |2 cas  |a doxorubicin, 23214-92-8, 25316-40-9; protein kinase B, 148640-14-6; tacrolimus, 104987-11-3; Molecular Chaperones; Receptors, Steroid; Tacrolimus Binding Proteins, 5.2.1.-; tacrolimus binding protein 4, 5.2.1.-; tacrolimus binding protein 5, 5.2.1.8 
040 |a Scopus  |b spa  |c AR-BaUEN  |d AR-BaUEN 
030 |a TENME 
100 1 |a Storer, C.L. 
245 1 0 |a FKBP51 and FKBP52 in signaling and disease 
260 |c 2011 
270 1 0 |m Cox, M.B.; The Border Biomedical Research Center and Department of Biological Sciences, University of Texas at El Paso, El Paso, TX 79968, United States; email: mbcox@utep.edu 
506 |2 openaire  |e Política editorial 
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520 3 |a FKBP51 and FKBP52 are diverse regulators of steroid hormone receptor signaling, including receptor maturation, hormone binding and nuclear translocation. Although structurally similar, they are functionally divergent, which is largely attributed to differences in the FK1 domain and the proline-rich loop. FKBP51 and FKBP52 have emerged as likely contributors to a variety of hormone-dependent diseases, including stress-related diseases, immune function, reproductive functions and a variety of cancers. In addition, recent studies have implicated FKBP51 and FKBP52 in Alzheimer's disease and other protein aggregation disorders. This review summarizes our current understanding of FKBP51 and FKBP52 interactions within the receptor-chaperone complex, their contributions to health and disease, and their potential as therapeutic targets for the treatment of thesediseases. © 2011 Elsevier Ltd.  |l eng 
536 |a Detalles de la financiación: National Institute on Aging 
536 |a Detalles de la financiación: National Institutes of Health, SC1GM084863 
536 |a Detalles de la financiación: Secretaría de Ciencia y Técnica, Universidad de Buenos Aires, R01NS073899, R00AG031291, X085 
536 |a Detalles de la financiación: Texas A and M University-Central Texas 
536 |a Detalles de la financiación: National Center for Research Resources, NCRR 
536 |a Detalles de la financiación: Agencia Nacional de Promoción Científica y Tecnológica, PICT2011-1170 
536 |a Detalles de la financiación: National Institute of General Medical Sciences 
536 |a Detalles de la financiación: National Institute of Neurological Disorders and Stroke 
536 |a Detalles de la financiación: The authors are supported in part by Grant 5G12RR008124 [to the Border Biomedical Research Center (BBRC)/University of Texas at El Paso] from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH). The contents of this article are solely the responsibility of the authors and do not necessarily represent the official views of NCRR or NIH. We thank the BBRC Biomolecule Analysis Core Facility (BACF), Tissue Culture Core Facility (TCF), and the DNA Analysis Core Facility (DACF) for use of instruments. M.B.C. is also supported in part by American Recovery and Reinvestment Act (ARRA) funds through Grant SC1GM084863 from the National Institute of General Medical Sciences, NIH. M.D.G. is supported by grants ANPCyT (PICT2011-1170) and UBACyT (X085). C.A.D. is supported by grants R01NS073899 and R00AG031291 from the National Institute of Neurological Disorders and Stroke and the National Institute on Aging, respectively. AKT serine/threonine protein kinase that regulates apoptosis, cell migration, transcription, proliferation and glucose metabolism. Antineoplastic therapy chemotherapy that targets all actively dividing cells. β-Importin during nuclear import, β-importin tethers incoming proteins to the nuclear pore complex. FKBP51 51-kDa FK506 binding protein that binds the immunosuppressive drug FK506 without initiating immunosuppression. FKBP52 52-kDa FK506 binding protein that binds the immunosppressive drug FK506 without initiating immunosuppression. FK1 domain FKBP12-like domain 1 of FKBP51 and FKPB52, responsible for binding to FK506, for PPIase activity and for steroid hormone receptor regulation. FK2 domain FKBP12-like domain 2, present in FKBP51 and FKBP52; differs slightly from the FK1 and lacks PPIase and FK506 binding ability. FK506 also called tacrolimus, a macrolide drug that complexes with FKBP12 and inhibits calcineurin phosphatase activity. This leads to immunosuppression by blocking T-cell signal transduction cascades and interleukin-2 transcription. Geldanamycin benzoquinone ansamycin antibiotic that directly binds HSP90 and inhibits its function. HSP90 the 90-kDa heat shock protein is a molecular chaperone involved in protein folding, tumor repression and cell signaling. Steroid hormone receptors require association with HSP90 to fold to a conformation capable of binding to a ligand. Hypothalamus pituitary adrenal (HPA) axis interactions between the hypothalamus, the pituitary gland and the adrenal glands are crucial parts of the neuroendocrine system. This pathway is responsible for the regulation of stress reactions, energy storage and output, emotion and affect, sexuality, digestion and the immune system. MHC II major histocompatibility complex class II molecules are located on subclasses of antigen-presenting cells and display extracellular protein fragments to CD4 + helper T cells to determine the immune response. NF-κB nuclear factor κ light-chain enhancer of activated B cells is a transcription factor complex found in most animal cells that regulates cellular responses to infections and stress. Nup62 nucleoporin 62 is a complex of proteins that associates with the importin αβ complex of the nuclear pore to assist in the import of proteins with nuclear localization signals. PPIase activity peptidyl prolyl isomerase activity catalyzes cis – trans isomerization reactions of peptide bonds involving the amino acid proline. PPIase activity is required for the proper folding of several, but not all, proteins. Protein aggregation disorders agglomeration of proteins occurs in diseases such as Alzheimer's disease, bovine spongiform encephalopathy (mad cow disease) and Huntington's disease. Radicicol also known as monorden, radicicol is a macrolactone antibiotic that binds HSP90 and alters its function. It also inhibits tyrosine kinase and is anti-angiogenic. Reticulosyte lysate assembly system cell-free assembly system that contains all the eukaryotic cofactors necessary for steroid hormone receptor folding and allows for reconstitution of the receptors with chaperone complexes in vitro . Tau tau proteins are found primarily in neurons of the central nervous system and normally help in microtubule stabilization. Defective folding of tau and the resultant agglomeration are associated with neurodegenerative diseases such as Alzheimer's and Parkinson's diseases. TPR domain the tetratricopeptide repeat is a structural motif used in protein–protein interactions. The TPR domains on FKBP51 and FKBP52 bind specifically to the extreme C terminus of HSP90. 
593 |a The Border Biomedical Research Center and Department of Biological Sciences, University of Texas at El Paso, El Paso, TX 79968, United States 
593 |a Departments of Molecular Medicine and Psychiatry, University of South Florida Alzheimer's Institute, Tampa, FL 33613, United States 
593 |a Instituto de Biología y Medicina Experimental (IBYME), CONICET (1428ADN) Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales (C1428EGA) Universidad de Buenos Aires, Buenos Aires, Argentina 
593 |a Max Planck Institute of Psychiatry, 80804 Munich, Germany 
690 1 0 |a ANDROGEN RECEPTOR 
690 1 0 |a ANTINEOPLASTIC AGENT 
690 1 0 |a DOXORUBICIN 
690 1 0 |a ESTROGEN RECEPTOR 
690 1 0 |a IMMUNOGLOBULIN ENHANCER BINDING PROTEIN 
690 1 0 |a MINERALOCORTICOID RECEPTOR 
690 1 0 |a MULTIPROTEIN COMPLEX 
690 1 0 |a PROGESTERONE RECEPTOR 
690 1 0 |a PROTEIN FKBP51 
690 1 0 |a PROTEIN FKBP52 
690 1 0 |a PROTEIN KINASE B 
690 1 0 |a RECEPTOR CHAPERONE COMPLEX 
690 1 0 |a REGULATOR PROTEIN 
690 1 0 |a STEROID HORMONE 
690 1 0 |a STEROID RECEPTOR 
690 1 0 |a TACROLIMUS 
690 1 0 |a UNCLASSIFIED DRUG 
690 1 0 |a ALZHEIMER DISEASE 
690 1 0 |a ANXIETY DISORDER 
690 1 0 |a BIPOLAR DISORDER 
690 1 0 |a BREAST CARCINOGENESIS 
690 1 0 |a BREAST TUMOR 
690 1 0 |a CELL PROLIFERATION 
690 1 0 |a CELLULAR DISTRIBUTION 
690 1 0 |a COMPLEX FORMATION 
690 1 0 |a DEPRESSION 
690 1 0 |a DISEASE ASSOCIATION 
690 1 0 |a DRUG TARGETING 
690 1 0 |a GENITAL SYSTEM 
690 1 0 |a HUMAN 
690 1 0 |a IMMUNE SYSTEM 
690 1 0 |a IMMUNOPATHOLOGY 
690 1 0 |a MENTAL STRESS 
690 1 0 |a METABOLIC DISORDER 
690 1 0 |a MOLECULAR PATHOLOGY 
690 1 0 |a NEUROPATHOLOGY 
690 1 0 |a NONHUMAN 
690 1 0 |a PATHOPHYSIOLOGY 
690 1 0 |a POSTTRAUMATIC STRESS DISORDER 
690 1 0 |a PRIORITY JOURNAL 
690 1 0 |a PROSTATE CANCER 
690 1 0 |a PROTEIN CONFORMATION 
690 1 0 |a PROTEIN FOLDING 
690 1 0 |a PROTEIN FUNCTION 
690 1 0 |a PROTEIN LOCALIZATION 
690 1 0 |a PROTEIN PROTEIN INTERACTION 
690 1 0 |a PROTEIN STRUCTURE 
690 1 0 |a REVIEW 
690 1 0 |a SCHIZOPHRENIA 
690 1 0 |a SIGNAL TRANSDUCTION 
690 1 0 |a TAUOPATHY 
690 1 0 |a ALZHEIMER DISEASE 
690 1 0 |a ANIMALS 
690 1 0 |a HUMANS 
690 1 0 |a MOLECULAR CHAPERONES 
690 1 0 |a MOLECULAR TARGETED THERAPY 
690 1 0 |a NEOPLASMS 
690 1 0 |a PROTEIN TRANSPORT 
690 1 0 |a RECEPTORS, STEROID 
690 1 0 |a SIGNAL TRANSDUCTION 
690 1 0 |a STRESS, PSYCHOLOGICAL 
690 1 0 |a TACROLIMUS BINDING PROTEINS 
653 0 0 |a fk 506 
700 1 |a Dickey, C.A. 
700 1 |a Galigniana, M.D. 
700 1 |a Rein, T. 
700 1 |a Cox, M.B. 
773 0 |d 2011  |g v. 22  |h pp. 481-490  |k n. 12  |p Trends Endocrinol. Metab.  |x 10432760  |w (AR-BaUEN)CENRE-7077  |t Trends in Endocrinology and Metabolism 
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