Artículo

Antunica-Noguerol, M.; Budziñski, M.L.; Druker, J.; Gassen, N.C.; Sokn, M.C.; Senin, S.; Aprile-Garcia, F.; Holsboer, F.; Rein, T.; Liberman, A.C.; Arzt, E. "The activity of the glucocorticoid receptor is regulated by SUMO conjugation to FKBP51" (2016) Cell Death and Differentiation. 23(10):1579-1591
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Abstract:

FK506-binding protein 51 (FKBP51) regulates the activity of the glucocorticoid receptor (GR), and is therefore a key mediator of the biological actions of glucocorticoids. However, the understanding of the molecular mechanisms that govern its activity remains limited. Here, we uncover a novel regulatory switch for GR activity by the post-translational modification of FKBP51 with small ubiquitin-like modifier (SUMO). The major SUMO-attachment site, lysine 422, is required for FKBP51-mediated inhibition of GR activity in hippocampal neuronal cells. Importantly, impairment of SUMO conjugation to FKBP51 impacts on GR-dependent neuronal signaling and differentiation. We demonstrate that SUMO conjugation to FKBP51 is enhanced by the E3 ligase PIAS4 and by environmental stresses such as heat shock, which impact on GR-dependent transcription. SUMO conjugation to FKBP51 regulates GR hormone-binding affinity and nuclear translocation by promoting FKBP51 interaction within the GR complex. SUMOylation-deficient FKBP51 fails to interact with Hsp90 and GR thus facilitating the recruitment of the closely related protein, FKBP52, which enhances GR transcriptional activity. Moreover, we show that the modification of FKBP51 with SUMO modulates its binding to Hsp90. Our data establish SUMO conjugation as a novel regulatory mechanism in the Hsp90 cochaperone activity of FKBP51 with a functional impact on GR signaling in a neuronal context.

Registro:

Documento: Artículo
Título:The activity of the glucocorticoid receptor is regulated by SUMO conjugation to FKBP51
Autor:Antunica-Noguerol, M.; Budziñski, M.L.; Druker, J.; Gassen, N.C.; Sokn, M.C.; Senin, S.; Aprile-Garcia, F.; Holsboer, F.; Rein, T.; Liberman, A.C.; Arzt, E.
Filiación:Instituto de Investigación en Biomedicina de Buenos Aires (IBioBA), CONICET, Partner Institute of the Max Planck Society, Godoy Cruz 2390, Buenos Aires, C1425FQD, Argentina
Departamento de Fisiología y Biología Molecular y Celular, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, C1428EGA, Argentina
Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Munich, 80804, Germany
Department of Clinical Research, Max Planck Institute of Psychiatry, Munich, 80804, Germany
Palabras clave:fk 506 binding protein; fk 506 binding protein 51; glucocorticoid receptor; lysine; SUMO protein; unclassified drug; fk 506 binding protein; glucocorticoid receptor; heat shock protein 90; PIAS4 protein, human; poly ADP ribose binding protein; protein inhibitor of activated STAT; animal experiment; Article; controlled study; drug conjugation; environmental stress; gene expression; heat shock; hormone binding; mouse; nerve cell differentiation; nerve fiber growth; nonhuman; priority journal; protein processing; regulatory mechanism; sumoylation; animal; Bagg albino mouse; biological model; genetic transcription; heat shock response; HEK293 cell line; human; metabolism; sumoylation; Animals; Heat-Shock Response; HEK293 Cells; HSP90 Heat-Shock Proteins; Humans; Lysine; Mice, Inbred BALB C; Models, Biological; Poly-ADP-Ribose Binding Proteins; Protein Inhibitors of Activated STAT; Receptors, Glucocorticoid; Sumoylation; Tacrolimus Binding Proteins; Transcription, Genetic
Año:2016
Volumen:23
Número:10
Página de inicio:1579
Página de fin:1591
DOI: http://dx.doi.org/10.1038/cdd.2016.44
Título revista:Cell Death and Differentiation
Título revista abreviado:Cell Death Differ.
ISSN:13509047
CODEN:CDDIE
CAS:lysine, 56-87-1, 6899-06-5, 70-54-2; HSP90 Heat-Shock Proteins; Lysine; PIAS4 protein, human; Poly-ADP-Ribose Binding Proteins; Protein Inhibitors of Activated STAT; Receptors, Glucocorticoid; Tacrolimus Binding Proteins
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_13509047_v23_n10_p1579_AntunicaNoguerol

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Citas:

---------- APA ----------
Antunica-Noguerol, M., Budziñski, M.L., Druker, J., Gassen, N.C., Sokn, M.C., Senin, S., Aprile-Garcia, F.,..., Arzt, E. (2016) . The activity of the glucocorticoid receptor is regulated by SUMO conjugation to FKBP51. Cell Death and Differentiation, 23(10), 1579-1591.
http://dx.doi.org/10.1038/cdd.2016.44
---------- CHICAGO ----------
Antunica-Noguerol, M., Budziñski, M.L., Druker, J., Gassen, N.C., Sokn, M.C., Senin, S., et al. "The activity of the glucocorticoid receptor is regulated by SUMO conjugation to FKBP51" . Cell Death and Differentiation 23, no. 10 (2016) : 1579-1591.
http://dx.doi.org/10.1038/cdd.2016.44
---------- MLA ----------
Antunica-Noguerol, M., Budziñski, M.L., Druker, J., Gassen, N.C., Sokn, M.C., Senin, S., et al. "The activity of the glucocorticoid receptor is regulated by SUMO conjugation to FKBP51" . Cell Death and Differentiation, vol. 23, no. 10, 2016, pp. 1579-1591.
http://dx.doi.org/10.1038/cdd.2016.44
---------- VANCOUVER ----------
Antunica-Noguerol, M., Budziñski, M.L., Druker, J., Gassen, N.C., Sokn, M.C., Senin, S., et al. The activity of the glucocorticoid receptor is regulated by SUMO conjugation to FKBP51. Cell Death Differ. 2016;23(10):1579-1591.
http://dx.doi.org/10.1038/cdd.2016.44