scholarly journals Glucocorticoid Receptor–DNA Interactions: Binding Energetics Are the Primary Determinant of Sequence-Specific Transcriptional Activity

2012 ◽  
Vol 422 (1) ◽  
pp. 18-32 ◽  
Author(s):  
David L. Bain ◽  
Qin Yang ◽  
Keith D. Connaghan ◽  
James P. Robblee ◽  
Michael T. Miura ◽  
...  
Keyword(s):  
Glucocorticoid Receptor ◽  
Transcriptional Activity ◽  
Dna Interactions ◽  
Binding Energetics ◽  
Primary Determinant

scholarly journals Small ubiquitin-related modifier-1 (SUMO-1) modification of the glucocorticoid receptor

2002 ◽  
Vol 367 (3) ◽  
pp. 907-911 ◽  
Author(s):  
Sha TIAN ◽  
Hetti POUKKA ◽  
Jorma J. PALVIMO ◽  
Olli A. JÄNNE
Keyword(s):  
Glucocorticoid Receptor ◽  
Transcriptional Activity ◽  
Receptor Function ◽  
Dna Interactions ◽  
Mouse Mammary Tumour Virus ◽  
Cellular Targets ◽  
Attachment Sites ◽  
Protein Dna Interactions ◽  
Regulate Protein ◽  
Virus Promoter

Small ubiquitin-related modifier-1 (SUMO-1) is covalently attached to many cellular targets to regulate protein—protein and protein—DNA interactions, as well as localization and stability of the target protein. The SUMO-1-conjugating E2 enzyme Ubc9 is known to interact with the glucocorticoid receptor (GR), a ligand-dependent transcription factor. In the present study, we show that GR is post-translationally modified by SUMO-1 (sumoylated) in a ligand-enhanced fashion. We identify experimentally three consensus SUMO attachment sites, two in the N-terminal transactivation region and one in the ligand-binding domain of GR. The two N-terminal sites are the major acceptor sites for SUMO-1 attachment. Mutation of these sites enhances transcriptional activity of GR on minimal promoters, but has no clear effect on the more complex mouse mammary tumour virus promoter. Thus SUMO-1 modification of GR influences receptor function in a promoter context-dependent fashion.

scholarly journals RSUME Enhances Glucocorticoid Receptor SUMOylation and Transcriptional Activity

2013 ◽  
Vol 33 (11) ◽  
pp. 2116-2127 ◽  
Author(s):  
J. Druker ◽  
A. C. Liberman ◽  
M. Antunica-Noguerol ◽  
J. Gerez ◽  
M. Paez-Pereda ◽  
...  
Keyword(s):  
Glucocorticoid Receptor ◽  
Transcriptional Activity

scholarly journals RanBPM, a Nuclear Protein That Interacts with and Regulates Transcriptional Activity of Androgen Receptor and Glucocorticoid Receptor

2002 ◽  
Vol 277 (50) ◽  
pp. 48020-48027 ◽  
Author(s):  
Mira A. Rao ◽  
Helen Cheng ◽  
Alandra N. Quayle ◽  
Hideo Nishitani ◽  
Colleen C. Nelson ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
Glucocorticoid Receptor ◽  
Transcriptional Activity ◽  
Nuclear Protein

scholarly journals The SRSF4-GAS5-Glucocorticoid Receptor Axis Regulates Ventricular Hypertrophy

2021 ◽  
Author(s):  
Javier Larrasa-Alonso ◽  
María Villalba ◽  
Carlos Martí-Gómez ◽  
Paula Ortiz-Sánchez ◽  
Marina López-Olañeta ◽  
...  
Keyword(s):  
Glucocorticoid Receptor ◽  
Cardiac Hypertrophy ◽  
Diastolic Dysfunction ◽  
Ventricular Hypertrophy ◽  
Transcriptional Activity ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Left Ventricular ◽  
Therapeutic Tools ◽  
Nucleotide Resolution

Rationale: RNA-binding proteins (RBPs) play critical roles in human biology and disease. Aberrant RBP expression affects various steps in RNA processing, altering the function of the target RNAs. The RBP serine/arginine-rich splicing factor 4 (SRSF4) has been linked to neuropathies and cancer. However, its role in the heart is completely unknown. Objective: To investigate the role of SRSF4 in the heart. Methods and Results: Echocardiography of mice specifically lacking SRSF4 in the heart (SRSF4 KO) revealed left ventricular hypertrophy and increased cardiomyocyte area, which led to progressive diastolic dysfunction with age. SRSF4 KO mice showed altered electrophysiological activity under isoproterenol-induced cardiac stress, with a post-QRS depression and a longer QT interval, indicating an elevated risk of sudden cardiac death. RNA-Seq analysis revealed expression changes in several long non-coding RNAs (lncRNAs), including GAS5 (growth arrest specific 5), which we identified as a direct SRSF4 target in cardiomyocytes by individual-nucleotide-resolution cross-linking and immuno-precipitation (iCLIP). GAS5 is a repressor of the glucocorticoid receptor (GR) and was downregulated in SRSF4 KO hearts. This corresponded with elevated GR transcriptional activity in cardiomyocytes, leading to increases in hypertrophy markers and cell size. Furthermore, hypertrophy in SRSF4 KO cardiomyocytes was reduced by overexpressing GAS5. Conclusions: Loss of SRSF4 expression results in cardiac hypertrophy, diastolic dysfunction, and abnormal repolarization. The molecular mechanism underlying this effect involves GAS5 downregulation and consequent elevation of GR transcriptional activity. Our findings may help to develop new therapeutic tools for the treatment of cardiac hypertrophy and myocardial pathology in Cushing's syndrome patients.

scholarly journals Glucocorticoid receptor (GR) β has intrinsic, GRα-independent transcriptional activity

2009 ◽  
Vol 381 (4) ◽  
pp. 671-675 ◽  
Author(s):  
Tomoshige Kino ◽  
Irini Manoli ◽  
Sujata Kelkar ◽  
Yonghong Wang ◽  
Yan A. Su ◽  
...  
Keyword(s):  
Glucocorticoid Receptor ◽  
Transcriptional Activity

scholarly journals The Smad6-Histone Deacetylase 3 Complex Silences the Transcriptional Activity of the Glucocorticoid Receptor

2005 ◽  
Vol 280 (51) ◽  
pp. 42067-42077 ◽  
Author(s):  
Takamasa Ichijo ◽  
Antonis Voutetakis ◽  
Ana P. Cotrim ◽  
Nisan Bhattachryya ◽  
Makiko Fujii ◽  
...  
Keyword(s):  
Glucocorticoid Receptor ◽  
Histone Deacetylase ◽  
Transcriptional Activity ◽  
Histone Deacetylase 3

Thermodynamics of sequence-specific glucocorticoid receptor-DNA interactions

Biochemistry ◽  
1994 ◽  
Vol 33 (19) ◽  
pp. 5955-5965 ◽  
Author(s):  
Thomas Lundbaeck ◽  
Johanna Zilliacus ◽  
Jan-Aake Gustafsson ◽  
Jan Carlstedt-Duke ◽  
Torleif Haerd
Keyword(s):  
Glucocorticoid Receptor ◽  
Dna Interactions

scholarly journals Peripheral CLOCK Regulates Target-Tissue Glucocorticoid Receptor Transcriptional Activity in a Circadian Fashion in Man

PLoS ONE ◽  
2011 ◽  
Vol 6 (9) ◽  
pp. e25612 ◽  
Author(s):  
Evangelia Charmandari ◽  
George P. Chrousos ◽  
George I. Lambrou ◽  
Aikaterini Pavlaki ◽  
Hisashi Koide ◽  
...  
Keyword(s):  
Glucocorticoid Receptor ◽  
Transcriptional Activity ◽  
Target Tissue ◽  
Peripheral Clock

scholarly journals Allosteric Effects of Dexamethasone and RU486 on Glucocorticoid Receptor-DNA Interactions

2001 ◽  
Vol 277 (2) ◽  
pp. 1538-1543 ◽  
Author(s):  
Shilpa Pandit ◽  
Wayne Geissler ◽  
Georgianna Harris ◽  
Ayesha Sitlani
Keyword(s):  
Glucocorticoid Receptor ◽  
Dna Interactions
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