scholarly journals Negative Correlation between the Diffusion Coefficient and Transcriptional Activity of the Glucocorticoid Receptor

2017 ◽  
Vol 18 (9) ◽  
pp. 1855 ◽  
Author(s):  
◽  
◽  
◽  
Keyword(s):  
Diffusion Coefficient ◽  
Glucocorticoid Receptor ◽  
Negative Correlation ◽  
Transcriptional Activity

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 Advanced trends in magnetic resonance imaging in assessment of lumbar intervertebral degenerative disk disease

2019 ◽  
Vol 50 (1) ◽  
Author(s):  
Rania Sobhy Abou Khadrah ◽  
Mohamed F. Dawoud ◽  
Ashraf Ali Abo-Elsafa ◽  
Amr M. Elkilany
Keyword(s):  
Diffusion Coefficient ◽  
Negative Correlation ◽  
Early Stage ◽  
T2 Mapping ◽  
Intervertebral Disk ◽  
Intervertebral Disk Degeneration ◽  
Disk Degeneration ◽  
Apparent Diffusion ◽  
Adc Values

Abstract Background T2 mapping and DWI are newly quantitated method for disk degeneration assessment; they were used in the determination of an early stage of intervertebral disk degeneration. T2 mapping was quantitatively sensitive for detecting the early stage and aging-related changes in intervertebral disk degeneration. Furthermore, T2 mapping and apparent diffusion coefficient values (ADC) in lumbar intervertebral disks indirectly correlated with the Pfirrmann grades in IVDD and age-related disk degeneration. The aim of this study is to evaluate the sensitivity of T2 mapping and apparent diffusion coefficient in the determination of an early stage of intervertebral disk degeneration. Results T2 relaxometry values were found to decrease with the increased disk degeneration except in grade V where it was found to be increased again. There was a negative correlation between T2 values and semi-quantitative grading (Pfirrmann Grading) of disk degeneration and T2 values were significantly different when comparing grade I to V. A T2 value of nucleus pulposus (NP) was more sensitive than annulus fibrosus (AF) and entire of the disk. ADC values were found to decrease with the increased degree of disk degeneration; there was a weakly significant negative correlation between age and T2 mapping values, ADC values of nucleus pulposus, and entire of disk. Conclusion T2 mapping was significantly different when comparing grade I to V while ADC value had a significant weak negative correlation with age, so T2 mapping and to a little extent ADC can be used for quantitative analysis of early disk generation seeking for early diagnosis and better management.

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

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

Substitution of arginine for cysteine 643 of the glucocorticoid receptor reduces its steroid-binding affinity and transcriptional activity

2002 ◽  
Vol 181 (1) ◽  
pp. 109-114 ◽  
Author(s):  
Michiyo Nagano ◽  
Takahiro Nakamura ◽  
Shingo Niimi ◽  
Tomofumi Fujino ◽  
Tetsuji Nishimura ◽  
...  
Keyword(s):  
Glucocorticoid Receptor ◽  
Binding Affinity ◽  
Transcriptional Activity ◽  
Steroid Binding

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 The Cytoskeletal Network Controls c-Jun Expression and Glucocorticoid Receptor Transcriptional Activity in an Antagonistic and Cell-Type-Specific Manner

1999 ◽  
Vol 19 (3) ◽  
pp. 1742-1750 ◽  
Author(s):  
Anat Oren ◽  
Avia Herschkovitz ◽  
Iris Ben-Dror ◽  
Vered Holdengreber ◽  
Yehuda Ben-Shaul ◽  
...  
Keyword(s):  
Glutamine Synthetase ◽  
Glucocorticoid Receptor ◽  
Cell Separation ◽  
Transcriptional Activity ◽  
Marker Gene ◽  
Mitogen Activated Protein Kinase ◽  
Cell Contact ◽  
Specific Gene ◽  
Functional Link ◽  
Cytoskeletal Network

ABSTRACT The physical and functional link between adhesion molecules and the cytoskeletal network suggests that the cytoskeleton might mediate the transduction of cell-to-cell contact signals, which often regulate growth and differentiation in an antagonistic manner. Depolymerization of the cytoskeleton in confluent cell cultures is reportedly sufficient to initiate DNA synthesis. Here we show that depolymerization of the cytoskeleton is also sufficient to repress differentiation-specific gene expression. Glutamine synthetase is a glia-specific differentiation marker gene whose expression in the retinal tissue is regulated by glucocorticoids and is ultimately dependent on glia-neuron cell contacts. Depolymerization of the actin or microtubule network in cells of the intact retina mimics the effects of cell separation, repressing glutamine synthetase induction by a mechanism that involves induction of c-Jun and inhibition of glucocorticoid receptor transcriptional activity. Depolymerization of the cytoskeleton activates JNK and p38 mitogen-activated protein kinase and induces c-Jun expression by a signaling pathway that depends on tyrosine kinase activity. Induction of c-Jun expression is restricted to Müller glial cells, the only cells in the tissue that express glutamine synthetase and maintain the ability to proliferate upon cell separation. Our results suggest that the cytoskeletal network might play a part in the transduction of cell contact signals to the nucleus.

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