Artículo

Presman, D.M.; Ogara, M.F.; Stortz, M.; Alvarez, L.D.; Pooley, J.R.; Schiltz, R.L.; Grøntved, L.; Johnson, T.A.; Mittelstadt, P.R.; Ashwell, J.D.; Ganesan, S.; Burton, G.; Levi, V.; Hager, G.L.; Pecci, A. "Live Cell Imaging Unveils Multiple Domain Requirements for In Vivo Dimerization of the Glucocorticoid Receptor" (2014) PLoS Biology. 12(3)
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Abstract:

Glucocorticoids are essential for life, but are also implicated in disease pathogenesis and may produce unwanted effects when given in high doses. Glucocorticoid receptor (GR) transcriptional activity and clinical outcome have been linked to its oligomerization state. Although a point mutation within the GR DNA-binding domain (GRdim mutant) has been reported as crucial for receptor dimerization and DNA binding, this assumption has recently been challenged. Here we have analyzed the GR oligomerization state in vivo using the number and brightness assay. Our results suggest a complete, reversible, and DNA-independent ligand-induced model for GR dimerization. We demonstrate that the GRdim forms dimers in vivo whereas adding another mutation in the ligand-binding domain (I634A) severely compromises homodimer formation. Contrary to dogma, no correlation between the GR monomeric/dimeric state and transcriptional activity was observed. Finally, the state of dimerization affected DNA binding only to a subset of GR binding sites. These results have major implications on future searches for therapeutic glucocorticoids with reduced side effects. © 2014.

Registro:

Documento: Artículo
Título:Live Cell Imaging Unveils Multiple Domain Requirements for In Vivo Dimerization of the Glucocorticoid Receptor
Autor:Presman, D.M.; Ogara, M.F.; Stortz, M.; Alvarez, L.D.; Pooley, J.R.; Schiltz, R.L.; Grøntved, L.; Johnson, T.A.; Mittelstadt, P.R.; Ashwell, J.D.; Ganesan, S.; Burton, G.; Levi, V.; Hager, G.L.; Pecci, A.
Filiación:Laboratory of Receptor Biology and Gene Expression, National Cancer Institute, NIH, Bethesda, MD, United States
Department of Biological Chemistry, School of Sciences (FCEN), University of Buenos Aires (UBA), Buenos Aires, Argentina
IFIBYNE-CONICET, School of Sciences (FCEN), University of Buenos Aires (UBA), Buenos Aires, Argentina
Department of Organic Chemistry/UMYMFOR-CONICET, School of Sciences (FCEN), University of Buenos Aires (UBA), Buenos Aires, Argentina
Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, University of Bristol, Bristol, United Kingdom
Laboratory of Immune Cell Biology, Center for Cancer Research, National Cancer Institute, Bethesda, MD, United States
Biological Imaging Section, Research Technologies Branch, National Institute of Allergy and Infectious Diseases, NI, Bethesda, MD, United States
Palabras clave:Animals; Cells, Cultured; DNA; Mice; Protein Multimerization; Protein Structure, Tertiary; Receptors, Glucocorticoid
Año:2014
Volumen:12
Número:3
DOI: http://dx.doi.org/10.1371/journal.pbio.1001813
Título revista:PLoS Biology
Título revista abreviado:PloS Biol.
ISSN:15449173
CODEN:PBLIB
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_15449173_v12_n3_p_Presman

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Citas:

---------- APA ----------
Presman, D.M., Ogara, M.F., Stortz, M., Alvarez, L.D., Pooley, J.R., Schiltz, R.L., Grøntved, L.,..., Pecci, A. (2014) . Live Cell Imaging Unveils Multiple Domain Requirements for In Vivo Dimerization of the Glucocorticoid Receptor. PLoS Biology, 12(3).
http://dx.doi.org/10.1371/journal.pbio.1001813
---------- CHICAGO ----------
Presman, D.M., Ogara, M.F., Stortz, M., Alvarez, L.D., Pooley, J.R., Schiltz, R.L., et al. "Live Cell Imaging Unveils Multiple Domain Requirements for In Vivo Dimerization of the Glucocorticoid Receptor" . PLoS Biology 12, no. 3 (2014).
http://dx.doi.org/10.1371/journal.pbio.1001813
---------- MLA ----------
Presman, D.M., Ogara, M.F., Stortz, M., Alvarez, L.D., Pooley, J.R., Schiltz, R.L., et al. "Live Cell Imaging Unveils Multiple Domain Requirements for In Vivo Dimerization of the Glucocorticoid Receptor" . PLoS Biology, vol. 12, no. 3, 2014.
http://dx.doi.org/10.1371/journal.pbio.1001813
---------- VANCOUVER ----------
Presman, D.M., Ogara, M.F., Stortz, M., Alvarez, L.D., Pooley, J.R., Schiltz, R.L., et al. Live Cell Imaging Unveils Multiple Domain Requirements for In Vivo Dimerization of the Glucocorticoid Receptor. PloS Biol. 2014;12(3).
http://dx.doi.org/10.1371/journal.pbio.1001813