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 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 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 Aberrant corticosteroid metabolism in tumor cells enables GR takeover in enzalutamide resistant prostate cancer

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Jianneng Li ◽  
Mohammad Alyamani ◽  
Ao Zhang ◽  
Kai-Hsiung Chang ◽  
Michael Berk ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Glucocorticoid Receptor ◽  
Tumor Cells ◽  
Target Genes ◽  
Hydroxysteroid Dehydrogenase ◽  
Mouse Xenograft ◽  
Ubiquitin E3 Ligase ◽  
Metabolic Mechanism ◽  
Stimulation Of

Prostate cancer is driven by androgen stimulation of the androgen receptor (AR). The next-generation AR antagonist, enzalutamide, prolongs survival, but resistance and lethal disease eventually prevail. Emerging data suggest that the glucocorticoid receptor (GR) is upregulated in this context, stimulating expression of AR-target genes that permit continued growth despite AR blockade. However, countering this mechanism by administration of GR antagonists is problematic because GR is essential for life. We show that enzalutamide treatment in human models of prostate cancer and patient tissues is accompanied by a ubiquitin E3-ligase, AMFR, mediating loss of 11β-hydroxysteroid dehydrogenase-2 (11β-HSD2), which otherwise inactivates cortisol, sustaining tumor cortisol concentrations to stimulate GR and enzalutamide resistance. Remarkably, reinstatement of 11β-HSD2 expression, or AMFR loss, reverses enzalutamide resistance in mouse xenograft tumors. Together, these findings reveal a surprising metabolic mechanism of enzalutamide resistance that may be targeted with a strategy that circumvents a requirement for systemic GR ablation.

scholarly journals Cooperative Interactions between Androgen Receptor (AR) and Heat-Shock Protein 27 Facilitate AR Transcriptional Activity

2007 ◽  
Vol 67 (21) ◽  
pp. 10455-10465 ◽  
Author(s):  
Amina Zoubeidi ◽  
Anousheh Zardan ◽  
Eliana Beraldi ◽  
Ladan Fazli ◽  
Richard Sowery ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Transcriptional Activity ◽  
Heat Shock Protein 27 ◽  
Cooperative Interactions

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

The RNA-binding and adaptor protein Sam68 modulates signal-dependent splicing and transcriptional activity of the androgen receptor

2008 ◽  
Vol 215 (1) ◽  
pp. 67-77 ◽  
Author(s):  
P Rajan ◽  
L Gaughan ◽  
C Dalgliesh ◽  
A El-Sherif ◽  
CN Robson ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
Transcriptional Activity ◽  
Rna Binding ◽  
Adaptor Protein
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