Receptores Nucleares / Nuclear Receptors

(See below the "English Version" section for a full translation into the English language)

Nuestro equipo de trabajo estudia la regulación funcional de proteínas pertenecientes a la súperfamilia de receptores nucleares. En particular, nos focalizamos en dilucidar el mecanismo por el cual las chaperonas moleculares influyen sobre el transporte de variados factores de transcripción y las consecuencias de tal relocalización subcelular sobre los procesos de diferenciación celular, proliferación y apoptosis.

Receptores Nucleares / Nuclear Receptors

  • Director

    Dr. Mario D. Galigniana

    Ph.D. (1996) Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires.

    Profesor Adjunto del Depto. de Química Biológica, Facultad de Ciencias Exactas y Naturales-UBA.

    Investigador Principal del CONICET.

    E-mail1: mgaligniana@conicet.gov.ar  /  E-mail2: mgali@qb.fcen.uba.ar

  • Investigadores Asistentes

    Dra. Alejandra Giselle Erlejman (Fac. Farmacia y Bioquímica, UBA). E-mail: erlejman@qb.fcen.uba.ar

    Dra. Ana A. Cauerhff (Fac. Farmacia y Bioquímica, UBA). E-mail: anacauer@qb.fcen.uba.ar

    Dra. Laura B. Matkovic (Fac. Ciencias Exactas y Naturales, UBA). E-mail: lmat@qb.fcen.uba.ar

  • Becarios Postdoctorales

    Dra. Gisela Ileana Mazaira (Fac. Ciencias Exactas y Naturales, UBA). E-mail: gmazaira@qb.fcen.uba.ar

  • Tesistas

    Lic. Alejandro Martín Molinari (Fac. Ciencias Exactas y Naturales, UBA). E-mail: ammolinari@qb.fcen.uba.ar

    Lic. Cristina del Rosario Daneri-Becerra (Fac. Química, Bioquímica y Farmacia, Universidad Nacional de San Luis). E-mail: bedanti@hotmail.com

    Lic. Sonia De Leo (Fac. Ciencias Exactas y Naturales, UBA). E-mail: sonydeleo@fibertel.com.ar

    Lic. Nadia Zgajnar (Universidad Nacional de Misiones). E-mail: nadiazgajnar@gmail.com

    Lic. María Fernanda Camisay (Fac. Ciencias Exactas y Naturales, UBA). E-mail: fer_1815@hotmail.com

  • Estudiantes

    Sr. Fernando Federicci (Fac. Ciencias Exactas y Naturales, UBA). E-mail: cs.federicci@gmail.com


     

Aviso / Posted Position

EL GRUPO DE TRABAJO NECESITA INCORPORAR A UN BECARIO POSTDOCTORAL Y UN INVESTIGADOR ASISTENTE, PREFERENTEMENTE (AUNQUE NO EXCLUYENTE) CON EXPERIENCIA EN EL CAMPO DE LAS NEUROCIENCIASENVIAR CV A: mgaligniana@conicet.gov.ar O BIEN A: mgali@qb.fcen.uba.ar

The research group is seeking to appoint a Post-doctoral Fellow and an Associate Researcher. Experience in the Neurosciences field is desirable (although not excludent). Please, send a CV to the above listed e-mail accounts

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Líneas de Investigación / Research Projects

PROYECTOS EN MARCHA

Si pudiéramos comprender los mecanismos moleculares que regulan la localización subcelular de factores de transcripción que son claves para el ciclo de vida de la célula, podríamos influir sobre los mismos con drogas que relocalicen a tales factores según sea necesario y conveniente. Es así que, por ejemplo, NFκB muestra una persistente localización nuclear en un alto porcentaje de tumores, mientras que en otros, p53 se excluye del núcleo, lo que previene sus efectos proapoptóticos. Resultaría entonces muy útil desde el punto de vista terapéutico revertir tal desbalance en la distribución subcelular de estas proteínas en las células tumorales. Nosotros analizamos la participación de inmunofilinas de alto peso molecular en el mecanismo de transporte y anclado de variados factores nucleares.

Se llaman inmunofilinas a proteínas que poseen un dominio con actividad de peptidil-prolil isomerasa, la gran mayoría de las cuales une drogas inmunosupresoras. Sólo las inmunofilinas de bajo peso molecular (FKBP12 y CyPA) adquieren acción inmunosupresora al unir la droga inmunosuprsora, pero no parece ser éste el caso para el resto de los miembros de la familia (FKBP52, FKBP51, FKBP38, CyP40, PP5, etc.). Las de mayor tamaño se expresan en abundancia y poseen características de chaperonas moleculares. Sin embargo, la mayoría de sus propiedades biológicas permanecen aún desconocidas. Recientemente, demostramos que el complejo FKBP52•hsp90 es requerido para que los receptores esteroidales interactúen con el complejo motor de dineína/dinactina, lo que favorece así su transporte al núcleo en presencia de la hormona. Al presente, a este modelo lo estamos extendiendo a otros factores nucleares tales como NFκB, HSF-1 y p53. Los hallazgos sugieren que tal regulación del retrotransporte podría ser un proceso que también afecta a factores nucleares de variada naturaleza, pero que comparten la propiedad de estar sujetos a la relocalización subcelular según el tipo de estímulo.

Las inmunofilinas también se concentran en el núcleo y actúan como moduladores transcripcionales. Así, FKBP51 posee efecto inhibitorio y FKBP52 es estimulatorio o neutro, dependiendo del tipo celular. Al presente, estamos abocados a determinar si estas proteínas participan en la organización estructural de la cromatina en los sitios donde la maquinaria transcripcional traduce la información codificada en los genes-blanco. La evidencia sugiere que FKBP52 sería un factor de retención nuclear del receptor de glucocorticoides (GR) facilitando su anclado a estructuras nucleares, mientras que FKBP51 favorecería su exclusión nuclear. Nuestro modelo propone que el balance de expresión diferencial entre ambas inmunofilinas sería uno de los factores que regularían el pleiotropismo funcional de GR en diferentes tejidos.

También hemos observado que FKBP51 se concentra en las mitocondrias y que, frente a diversos estímulos, migra de manera rápida y reversible al núcleo. Ello nos llevó a estudiar el efecto de FKBP51 sobre la apoptosis, y demostramos su acción antiapoptótica. Al inhibir la muerte celular, es probable que FKBP51 participe de los procesos tumorales. Esto nos llevó a estudiar las propiedades de FKBP51 en variados tipos celulares tumorales y en biopsias normales y patológicas. Los estudios presentes se extienden de manera integrada al rol de las inmunofilinas sobre la actividad de otros factores relacionados con el control de ciclo de vida y muerte celular y con una proteína esencial para mantener la estructura cromosómica luego de cada división de la célula, la transcriptasa reversa de la telomerasa (TERT).

Nuestro grupo también estudia la capacidad de las chaperonas moleculares de regular la diferenciación neuronal a partir de células embrionarias parcial o totalmente indiferenciadas, así como de participar en el proceso de transdiferenciación, es decir, la reprogramación de células comprometidas con un cierto linaje hacia otro diferente. Los estudios abarcan desde los cambios fenotípicos de las células en cultivo, los cambios asociados a la estructura nuclear y a la arquitectura del citoesqueleto, hasta los efectos in vivo en modelos animales en donde las immunofilinas son utilizadas como blancos farmacológicos para la neurorregeneración y la neuroprotección.

En el laboratorio también se realizan estudios relacionados con la capacidad de los receptores esteroidales de reconocer a esteroides que posean ciertas propiedades conformacionales y de gatillar determinados efectos biológicos. Los estudios se focalizan fundamentalmente (pero no exclusivamente) en la función glucocorticoide y mineralocorticoide, y comprenden desde los clásicos experimentos funcionales in vivo hasta el análisis de las propiedades moleculares del mecanismo de acción del complejo hormona-receptor.

English Version

Laboratory of Nuclear Receptors

Laboratory of Nuclear Receptors

Our group studies the functional regulation of proteins belonging to the nuclear receptor superfamily. In particular, we are focused on the elucidation of the molecular mechanism by which molecular chaperones affect the subcellular transport of a variety of transcription factors and the biological consequences of this redistribution in processes such as cell differentiation, cell proliferation and apoptosis.

 

Group Leader:

Dr. Mario D. Galigniana

Ph.D. (1996) School of Pharmacy & Biochemistry of the University of Buenos Aires (UBA).

Assisstant Professor, Biological Chemistry Department of the Exact & Natural Sciences School, UBA.

Principal Investigator of the Argentine Research Council (CONICET).

 

Research Team:

Assistant Researchers: Dr. Alejandra Giselle Erlejman (The UBA Pharm & Biochem School), Dra. Mariana Lagadari (Fiederich Schiller Universität, Jena, Germany), Dr. Laura Matkovic (The UBA Exact & Nat Sci Sch). Postdoctoral Fellows: Dr. Mayra Yossixca Machado-Rada (Simón Bolívar University, Caracas, Venezuela). Ph.D. Students: Biol. Gisela Ileana Mazaira (The UBA Exact & Nat Sci Sch), Biol. Sonia De Leo (The UBA Exact & Nat Sci Sch), Biol. Alejandro Martín Molinari (The UBA Exact & Nat Sci Sch), Biol. Cristina del Rosario Daneri-Becerra (The Univ. of San Luis Chem, Biochem & Pharm Sch), Genet. Nadia Romina Zgajnar (Misiones University), Biol. Luzia Thea Ballmer (Universität Freiburg, Alemania). Undergraduate Students: MsMaría Fernanda Camisay (The UBA Exact & Nat Sci Sch).

 

Research Projects:

Many proteins shuttle dynamically between the cytoplasm and the nucleus. Ideally, the biological function of several nuclear factors could be regulated if we can identify the mechanism by which they reach their sites of action. For example, NFκB is persistently nuclear in many cancer cells and this feature has been related to tumor development. On the other hand, p53 activation promotes cell-cycle arrest and apoptotic cell death, and p53 mislocalization in the cytoplasm is responsible for tumor development. Unlike NFκB, localizing p53 to the nucleus would be desirable for the control of cell survival. Consequently, it would be extremely useful from the therapeutic point of view if we could affect the subcellular localization of these proteins by using specific drugs. We analyze the role of high molecular weight immunophilins in the mechanism of transport and anchorage to cell structures of several nuclear factors.

Immunophilins are a family of proteins that possesses peptidyprolyl isomerase enzymatic activity. Only the smallest members of this family (FKBP12 and CyPA) acquire immunosuppressive action upon drug binding. It seems that this is not the case for the other members of the family (FKBP52, FKBP51, FKBP38, CyP40, PP5, etc.). These immunophilinas are abundantly expressed and show properties of molecular chaperones. Nonetheless, most of their biological actions are still unknown. We have recently demonstrated that the FKBP52•hsp90 complex binds the dynein/dynactin motor complex, therefore being necessary for the hormone-dependent retrotransport of steroid receptors. Currently, this model is being extended to other members of the nuclear receptor family, such as NFκB, HSF-1 and p53. Our findings suggest that the mechanism of transport first described for steroid receptors is also used by other nuclear factors that are subject of subcellular redistribution upon cell stimulation with specific stimuli.

Immunophilins are also present in the nucleus and affect the transcriptional mechanism of the cell. FKBP51 has generally been regarded to be a negative regulator of steroid receptors, whereas FKBP52 is a positive or neutral regulator depending on the receptor and the cell type. Our research is currently focused on the elucidation of the molecular mechanism of these effects and is exploring whether immunophilins participate in the rearrangement of the chromatin architecture where the target-genes are located. Inasmuch as FKBP52 favors the nuclear retention of the glucocorticoid receptor (GR) to nuclear speckles and FKBP51 favors GR nuclear exclusion, we postulate that the balance of expression between these two immunophilins could be one of the reasons for the pleiotropic effects of GR in different tissues.

Because we have observed that FKBP51 concentrates in mitochondria and shuttles between this organelle and the nucleus, a possible involvement of the immunophilins with apoptosis is being studied. FKP51 shows antiapoptotic action and all its properties are preserved by several tumor cell lines and cancer tissues (as suggested by analysis of biopsies). Our studies are also extended in an integrated fashion to other factors related to the cycles of cell death and replication such as the telomerase reverse transcriptase (TERT).

Our group also studies the capability of molecular chaperones to regulate neurite outgrowth and neuron differentiation of embryonic cells, as well as the trans-differentiation process into neurons. Current studies analyze the phenotypic changes of the cells, molecular markers, modifications of the nuclear and cytoskeletal architecture, and in vivo studies in animal models, where immunophilins are being tested as potential pharmacologic targets for neuronal regeneration and neuroprotection.

The laboratory also performs studies on steroid structure-biological activity relationship. Most of the studies attempt to correlate steroid conformation with the binding capacity to steroid receptors and biological activity, in particular (but not exclusively) the mineralocorticoid and glucocorticoid effects. The studies include a broad range of aspects of the effect, i.e., from classical in vivo bioassays to the mechanistic details of the hormone-receptor complex.

Publicaciones Seleccionadas / Selected Publications

Desde 2000 / From 2000

82. Michelini F, Bueno CA, Molinari AM, Galigniana MD, Galagovsky LR, Alché LE, Ramirez JA (2015) Synthetic stigmastanes with dual antiherpetic and immunomodulating activities inhibit ERK and Akt signaling pathways without binding to glucocorticoid receptors. Biochimica et Biophysica Acta (General Subjects). En prensa.

81. Galigniana MD (2015) Editorial: Immunophilins, Protein Chemistry and Cell Biology of a Promising New Class of Drug Targets. Current Molecular Pharmacology. En prensa.

80. Lagadari M, De Leo SA, Camisay MF, Galigniana MD, Erlejman AG (2015) Regulation of NF-kB signalling cascade by immunophilins. Current Molecular Pharmacology. En prensa.

79. Mazaira GI, Camisay MF, De Leo SA, Erlejman AG, Galigniana MD (2015) Biological relevance of Hsp90-binding immunophilins in cancer development and treatment. International Journal of Cancer. En prensa.

78. Dávola ME, Mazaira GI, Galigniana MD, Alché LE, Ramírez JA, Barquero AA. (2015) Synthetic pregnenolone derivatives as antiviral agents against acyclovir-resistant isolates of Herpes Simplex Virus Type 1. Antiviral Research 122:55-63.

77. Sayan Dutta Gupta S, Bommaka MK, Mazaira GI, Galigniana MD, Satya CV, Naryanasamy S, Gowrishankar L, Raghavendra NM (2015) Molecular docking study, synthesis and biological evaluation of Mannich bases as Hsp90 inhibitors. International Journal of Biological Macromolecules 80:253-259. 

76. Dutta Gupta S, RevathiB., Mazaira GI, Galigniana MD, Subrahmanyam CVS, Gowrishankar NL, RaghavendraNM (2015)  2,4-dihydroxy benzaldehyde derived Schiff bases as small molecule Hsp90 inhibitors: Rational identification of a new anticancer lead.  Bioorganic Chemistry 59: 97-105.

75. Mazaira GI, Erlejman AG, Galigniana MD (2015) Molecular chaperones shape steroid receptor action and pharmacologic strategies. Journal of Cell & Molecular Biology. Vol. 1 (1) 004.

74. Mazaira GI, Lagadari M, Erlejman AG, Galigniana MD (2014) The emerging role of TPR-domain immunophilins in the mechanism of action of steroid receptors. Nuclear Receptor Research, Vol. 1, ID 101094, 17 pages, doi:10.11131/2014/101094.

73. Napimoga MH, Galigniana MD, Migliorini Figueira AC, Onate SA, Castro-Obregon S (2014) Editorial:  Contributions from Latin America. Nuclear Receptor Research, Vol. 1, ID 101149, 3 pages, doi:10.11131/2014/101149

72. Erlejman AG, De Leo SA, Mazaira GI, Molinari AM, Camisay MF, Fontana V, Cox MB, Piwien-Pilipuk G,Galigniana MD (2014)  NF-kB transcriptional activity is modulated by FK506-binding proteins FKBP51 and FKBP52: A role for peptidyl-prolyl isomerase activity. Journal of Biological Chemistry 289: 26263–26276.

71. Erlejman AG, Lagadari M, Cox M, Galigniana MD (2014) Molecular chaperone activity of TPR-domain immunophilins. Current Protein & Peptide Science 15: 205-215.

68. Galigniana MD (2014) Editorial: The biology of molecular chaperones-Very complex activities for quite simple proteins. Current Protein & Peptide Science 15: 169-170.

70. Dutta Gupta S, Snigdha D, Mazaira GI, Galigniana MD, Subrahmanyam CV, Gowrishankar NL, Raghavendra NM (2014) Molecular docking study, synthesis and biological evaluation of Schiff bases as Hsp90 inhibitors. Biomedicine & Pharmacotherapy 68:369-376.

69. Toneatto J, Guber S, Charó NL, Susperreguy S, Schwartz J, Galigniana M, Piwien-Pilipuk G (2013) Dynamic mitochondrial-nuclear redistribution of the immunophilin FKBP51 is regulated by PKA signaling pathway to control gene expression in the process of adipocyte differentiation. Journal of Cell Science 126:5357-5368.

68. 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. Biochimica et Biophysica Acta (Gene Reg Mech) 1839:71-87.

67. Molinari A, Machado M, Mazaira G, Erlejman A,Galigniana MD (2013) Molecular basis of mineralo-corticoid receptor action in the nervous system. CNS Neurological Disorders–Drug Targets 12:1163-1174.

66. Galigniana MD (2013) Editorial: Steroid-dependent management of biological responses in the nervous system. CNS Neurological Disorders–Drug Targets 12:1143-1145.

65. Erlejman AG, Lagadari M, Galigniana MD (2013) Hsp90-binding immunophilins as a potential new platform for drug treatment. Future Medicinal Chemistry 5:591-607.

64. Galigniana MD (2013) When the Cell Stress Society International became South American: Meeting report of the IX International Workshop on the Molecular Biology of Stress Responses. CellStress & Chaperones 18:3-9.

63. Galigniana MD (2012) Steroid receptor coupling becomes nuclear. Chemistry & Biology 19:662-663.

62. Galigniana NM, Ballmer LT, Toneatto J, Erlejman AG, Lagadari M, Galigniana MD (2012) Regulation of the glucocorticoid response to stress-related disorders by the Hsp90-binding immunophilin FKBP51. Journal of Neurochemistry122: 4-18.

61. Quintá HR, Galigniana MD(2012) The neuroregenerative mechanism mediated by the Hspp90-binding immunophilin FKBP52 resembles the early steps of neuronal differentiation. Bristish Journal of Pharmacology. 166:637-49.

60. Brookes JC, Galigniana MD, Harker AH, Stoneham AM, Vinson GP (2012)System among the corticosteroids: Specificity and molecular dynamics. Journal of the Royal Society Interface 9:43-53.

59. Quintá HR, Galigniana NM, Daneri-Becerra CR, Erlejman AG, Lagadari, M, Galigniana MD (2011) Housekeeping role of heat-shock proteins and immunophilins in the organization of cytoskeleton involves early recruitment to nascent filaments. Cellular Signalling 23:1907-1920.

58. Gallo LI, Lagadari M, Piwien Pilipuk G, Galigniana MD. (2011)TPR-domain immunophilin FKBP51 is a novel mitochondrial factor with antiapoptotic function. Journal of Biological Chemistry 286:30152-60

57. Sivils J, Storer CL, Galigniana MD, Cox MB (2011) Regulation of steroid hormone receptor function by the 52-kDa FK506-binding protein (FKBP52).  Currents Opinion in Pharmacology. 11:314-319.

56. StorerCL, Dickey C, Galigniana MD, Rein T, Cox M (2011) Roles for the 51-kDa and 52-kDa FK506-binding proteins in signaling and disease. Trends in Endocrinology & Metabolism 22:481-490.

55-  Quinta HR, Maschi D, Gomez-Sanchez C, Piwien-Pilipuk G, Galigniana MD (2010) Subcellular rearrangement of hsp90-binding immunophilins accompanies neuronal differentiation and neurite outgrowth. Journal of Neurochemistry. 115:716-734.

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

53-  Galigniana MD, Erlejman AG., Monte M, Gomez-Sanchez C, Piwien-Pilipuk G (2010) The hsp90-FKBP52 complex links the mineralocorticoid receptor to motor proteins and persists bound to the receptor in early nuclear events. Molecular & Cellular Biology30:1285-1298.

52-  Echeverría PC, Mazaira G, Erlejman A, Gómez Sánchez 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. Molecular & Cellular Biology29: 4788-4797.

51-  Colo G, Rubio M, Nojek I, Echeverría 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 27:2430-2444.

50-  Gallo LI, Ghini A, Piwien G, Galigniana MD (2007) Differential recruitment of tetratricopeptide repeat domain immunophilins to the mineralocorticoid receptor influences both heat-shock protein 90-dependent retrotransport and hormone-dependent transcriptional activity. Biochemsitry 46:14044-14057.

49-  Piwien Pilipuk G, Vinson GP, Gomez Sanchez C, Galigniana MD (2007) Evidence for an NL1-independent nuclear translocation of the mineralocorticoid receptor in permeabilized cells. Biochemistry

46:1389-1397.

48-   Salatino M, Beguelin W, Peters MG, Carnevale R, Proietti CJ, Galigniana MD, Vedoy CG, Schillaci R, Charreau EH, Sogayar MC, Elizalde PV (2006) Progestin-induced caveolin-1 expression mediates breast cancer cell proliferation. Oncogene 25:7723-7739.

47-  Aviezer-Hagai K, Skovorodnikova J, Galigniana MD, Farchi PO, Efrat Y, von Koskull-Doring P, Ohad N, Breiman A (2007) Arabidopsis immunophilins ROF1 (AtFKBP62) and ROF2 (AkFKBP65) exhibit tissue specificity, are heat-stress induced, and bind hsp90.Plant Molecular Biology63:237-255.

46-  Presman DM, Hoijman E, Ceballos NR, Galigniana MD, Pecci A (2006) Melatonin inhibits glucocorticoid receptor nuclear translocation in mouse thymocytes. Endocrinology 147:5452-5459.

45-  Harrell JM, Murphy PJM, Morishima Y, Chen H, Mansfield JF, Galigniana MD, Pratt WB (2004) Evidence for glucocorticoid receptor transport on microtubules by dynein. Journal of Biological Chemistry 279:54647-54654.

44-  Galigniana MD, Morishima Y, Gallay PA, Pratt WB (2004) Cyclophilin-A is bound through its peptidylprolyl isomerase domain to the cytoplasmic dynein motor protein complex. Journal of Biological Chemistry 279:55754-55759.

43- Murphy PJ, Galigniana MD, Harrell JM, Lujngman M, Pratt WB (2004) Pifithrin-α is a specific inhibitor of p53 signaling after interaction of the tumor suppressor protein with hsp90 and its nuclear translocation. Journal of Biological Chemistry 279:30195-30201.

42. Galigniana MD, Harrell JM, O’Hagen HM, Ljungman M, Pratt WB (2004) Hsp90-binding immunophilins link p53 to dynein during p53 transport to the nucleus. Journal of Biological Chemistry

279: 22483-22489.

41. Pratt WB, Galigniana MD, P.Murphy (2004) Role of molecular chaperones in steroid receptor action. Essays in Biochemistry 40: 41-58.

40. Galigniana MD, Piwien Pilipuk G (2004) Activation of the ligand-mineralocorticoid receptor functional unit by ancient, classical, and novel ligands. Structure-activity-relationship. Vitamins & Hormones 69: 31-68.

39. Pratt WB, Galigniana MD, Harrell JM, DeFranco D (2004) Role of hsp90 and the hsp90-binding immunophilins in signalling protein movement. Cellular Signalling 16: 857-872.

38. Galigniana MD, Piwien Pilipuk G, Kanelakis KC, Burton G, Lantos CP (2004) Molecular mechanism of activation and nuclear translocation of the mineralocorticoid receptor upon binding of novel pregnanesteroids . Molecular & Cellular Endocrinology 217: 167-179.

37. Galigniana MD, Harrell JM, Housley PR, Patterson C, Fisher SK, W.Pratt (2004) Retrograde transport of the GR in neurites requires dynamic assembly of complexes with hsp90 and is linked to the CHIP component of the proteosome.  Molecular Brain Research 123:27-36.

36. Piwien Pilipuk G, Galigniana MD, Schwartz J (2003) Subnuclear localization of C/EBPβ is regulated by growth hormone and dependent on MAPK. Journal of Biological Chemistry 278:35668-35677.

35. Murphy PJ, Morishima Y, Simons S, Mansfield JF, Galigniana MD, Pratt WP (2003) Visualization and mechanism of assembly of a glucocorticoid receptor-hsp70 complex primed by subsequent hsp90-dependent opening of the steroid binding cleft. Journal of Biological Chemistry 278:34764-34773.

34. Ríos MC, Mazzetti MB, Galigniana MD, Aldonatti C, Tomio JM, San Martín L (2002) The decrease in uroporphyrinogen activity induced by ethanol predisposes the development of porphyria and accelerates xenobiotic-triggered porphyria, regardless of hepatic damage. Brazilian Journal of Medical & Biological Research11:1273-1283.

33. Galigniana MD, Harrell JM, Murphy JP, Radanyi C, Renoir JM, Zhang M, Pratt WB (2002) Binding of hsp-90-associated immunophilins to cytoplasmic dynein: direct binding and in vivo evidence that the peptidylprolyl isomerase domain is a dynein interaction  domain. Biochemistry 41:13602-13619.

32.Piwien Pilipuk G, Kanelakis K, Ghini A,Lantos C, Litwack G,Burton G, Galigniana MD (2002)

Modification of an essential amino group in the mineralocorticoid receptor evidences a differential conformational change of the receptor protein upon binding of antagonists, natural agonists and the synthetic agonist 11,19-oxido-progesterone.Biochimica et Biophysica Acta (Mol Cell Res) 1589, 31-48.

31. Vicent GP,Pecci A, Ghini AA, Piwien Pilipuk G, Galigniana MD (2002) Differences in nuclear retention characteristics of agonist-activated glucocorticoid receptor may determine specific biological responses. Experimental Cell Research 276:142-154 – published in the “Highlight Section”-

30. Piwien Pilipuk G, Ayala A, Machado A, Galigniana MD (2002) Impairment of mineralocorticoid receptor-dependent biological response by oxidative stress and ageing. Correlation with post-translational modification of MR and decreased ADP-ribosylatable level of EF-2 in kidney cells. Journal of Biological Chemistry 277, 11896-11903.

29. Harrell JM, Kurek I, Breiman A, Radanyi C, Renoir JM, Pratt WB, Galigniana MD (2002) All of the protein interactions that link steroid receptor-hsp90-immunophilin heterocomplexes to cytoplasmic dynein are common to plant and animal cells. Biochemistry 41, 5581-5587.

28. Piwien-Pilipuk G, Kanelakis KC, Galigniana MD (2002) Correlation between pregnanesteroid conformation, receptor affinity and antinatriuretic effect. European Journal of Pharmacology 454:131-143.

27. Galigniana MD, Radanyi C, Renoir JM, Housley PR, Pratt WB 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.Journal of Biological Chemistry 276, 14884-14889.

26. Murphy J, Kanelakis KC, Morishima Y, Galigniana MD, Pratt WB (2001) Stoichiometry, abundance, and functional significance of the hsp90/hsp70-based multiprotein chaperone machinery in reticulocyte lysate. Journal of Biological Chemistry276:30092-30098.

25. Houshyar H, Galigniana MD, Pratt WB, Woods JH (2001) Chronic morphine treatment alters pituitary-adrenal negative feedback sensitivity and downregulates glucocorticoid receptors in the rat brain.

Journal of Neuroendocrinology13:875-886.

24. Galigniana MD, Vicent GP, Piwien Pilipuk G, Burton G, Lantos CP (2000) Molecular mechanism of action of the potent sodium-retaining steroid 11,19-oxidoprogesterone. Molecular Pharmacology 58:58-70.

23. Kanelakis KC, Murphy P, Morishima Y, Toft D, Galigniana MD, Pratt WB (2000) Hsp70 interacting protein Hip does not affect glucocorticoid receptor folding by the hsp90-based chaperone machinery except to oppose the effect of BAG-1.  Biochemistry 39:14314-14321.

22. Piwien Pilipuk G, Galigniana MD (2000)  Oxidative stress induced by L-buthionine-(S,R)-sulfoximine, a selective inhibitior of the glutathione metabolism, inhibits the mouse kidney mineralocorticoid receptor function. Biochimica et Biophysica Acta (Mol Cell Res) 1495:263-280.

21. Galigniana MD (2000) Functional regulation of corticosteroid receptors by phosphorylation and redox potential. Current Topics in Steroid Research 3:1-22. 

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