scholarly journals The Ubiquitin-Conjugating Enzyme UBCH7 Acts as a Coactivator for Steroid Hormone Receptors

2004 ◽  
Vol 24 (19) ◽  
pp. 8716-8726 ◽  
Author(s):  
Seema Verma ◽  
Ayesha Ismail ◽  
Xiuhua Gao ◽  
Guilian Fu ◽  
Xiaotao Li ◽  
...  
Keyword(s):  
Hormone Receptors ◽  
Steroid Hormone ◽  
Steroid Receptor ◽  
Steroid Hormone Receptors ◽  
Proper Function ◽  
Dependent Manner ◽  
Ubiquitin Conjugating Enzyme ◽  
Receptor Transactivation ◽  
Conjugating Enzyme

ABSTRACT We investigated the role of the ubiquitin-conjugating enzyme UBCH7 in nuclear receptor transactivation. Using transient transfection assays, we demonstrated that UBCH7 modulates the transcriptional activity of progesterone receptor (PR) and glucocorticoid, androgen, and retinoic acid receptors in a hormone-dependent manner and that the ubiquitin conjugation activity of UBCH7 is required for its ability to potentiate transactivation by steroid hormone receptors (SHR). However, UBCH7 showed no significant effect on the transactivation functions of p53 and VP-16 activation domain. Depletion of endogenous UBCH7 protein by small interfering RNAs suggests that UBCH7 is required for the proper function of SHR. Furthermore, a chromatin immunoprecipitation assay demonstrated the hormone-dependent recruitment of UBCH7 onto estrogen receptor- and PR-responsive promoters. Additionally, we show that UBCH7 and E6-associated protein (E6-AP) synergistically enhance PR transactivation. We also demonstrate that UBCH7 interacts with steroid receptor coactivator 1 (SRC-1) and that UBCH7 coactivation function is dependent on SRC-1. Taken together, our results reveal the possible role of UBCH7 in steroid receptor transactivation and provide insights into the mechanism of action of UBCH7 in receptor function.

877 ROLE OF STEROID HORMONE RECEPTORS ON FORMATION AND PROGRESSION OF BLADDER CARCINOMA

2011 ◽  
Vol 185 (4S) ◽  
Author(s):  
Gholamreza Pourmand ◽  
Sepehr Salem ◽  
Abdolrasoul Mehrsai ◽  
Farid Kosari
Keyword(s):  
Bladder Carcinoma ◽  
Hormone Receptors ◽  
Steroid Hormone ◽  
Steroid Hormone Receptors

scholarly journals Hsp90 Heterocomplexes Regulate Steroid Hormone Receptors: From Stress Response to Psychiatric Disease

2018 ◽  
Vol 20 (1) ◽  
pp. 79 ◽  
Author(s):  
Jeremy Baker ◽  
Ilayda Ozsan ◽  
Santiago Rodriguez Ospina ◽  
Danielle Gulick ◽  
Laura Blair
Keyword(s):  
Stress Response ◽  
Hormone Receptors ◽  
Steroid Hormone ◽  
Steroid Receptor ◽  
Steroid Hormone Receptors ◽  
Psychiatric Disease ◽  
Post Traumatic Stress ◽  
Fk506 Binding Protein ◽  
Structural Regulation ◽  
And Function

The hypothalamus-pituitary-adrenal (HPA) axis directly controls the stress response. Dysregulation of this neuroendocrine system is a common feature among psychiatric disorders. Steroid hormone receptors, like glucocorticoid receptor (GR), function as transcription factors of a diverse set of genes upon activation. This activity is regulated by molecular chaperone heterocomplexes. Much is known about the structure and function of these GR/heterocomplexes. There is strong evidence suggesting altered regulation of steroid receptor hormones by chaperones, particularly the 51 kDa FK506-binding protein (FKBP51), may work with environmental factors to increase susceptibility to various psychiatric illnesses including post-traumatic stress disorder (PTSD), major depressive disorder (MDD), and anxiety. This review highlights the regulation of steroid receptor dynamics by the 90kDa heat shock protein (Hsp90)/cochaperone heterocomplexes with an in depth look at how the structural regulation and imbalances in cochaperones can cause functional effects on GR activity. Links between the stress response and circadian systems and the development of novel chaperone-targeting therapeutics are also discussed.

MP88-14 ROLE OF STEROID HORMONE RECEPTORS IN FORMATION AND PROGRESSION OF BLADDER CARCINOMA: A CASE-CONTROL STUDY

2016 ◽  
Vol 195 (4S) ◽  
Author(s):  
Gholamreza Pourmand ◽  
Rahil Mashhadi ◽  
Farid Kosari ◽  
Abdolrasoul Mehrsai ◽  
Sepehr Salem ◽  
...  
Keyword(s):  
Bladder Carcinoma ◽  
Hormone Receptors ◽  
Case Control Study ◽  
Steroid Hormone ◽  
Case Control ◽  
Steroid Hormone Receptors ◽  
Control Study

Beyond the HPA-axis: The role of the gonadal steroid hormone receptors in modulating stress-related responses in an animal model of PTSD

2015 ◽  
Vol 25 (6) ◽  
pp. 944-957 ◽  
Author(s):  
Daphna Fenchel ◽  
Yechiel Levkovitz ◽  
Ella Vainer ◽  
Zeev Kaplan ◽  
Joseph Zohar ◽  
...  
Keyword(s):  
Animal Model ◽  
Hpa Axis ◽  
Hormone Receptors ◽  
Steroid Hormone ◽  
Steroid Hormone Receptors ◽  
Gonadal Steroid

scholarly journals The Role of Steroid Hormone Receptors in Urothelial Tumorigenesis

Cancers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2155
Author(s):  
Hiroki Ide ◽  
Hiroshi Miyamoto
Keyword(s):  
Estrogen Receptor ◽  
Androgen Receptor ◽  
Glucocorticoid Receptor ◽  
Hormone Receptors ◽  
Steroid Hormone ◽  
Tumor Development ◽  
Estrogen Receptor Α ◽  
Estrogen Receptor Β ◽  
Steroid Hormone Receptors

Preclinical and/or clinical evidence has indicated a potential role of steroid hormone-mediated signaling pathways in the development of various neoplastic diseases, while precise mechanisms for the functions of specific receptors remain poorly understood. Specifically, in urothelial cancer where sex-related differences particularly in its incidence are noted, activation of sex hormone receptors, such as androgen receptor and estrogen receptor-β, has been associated with the induction of tumor development. More recently, glucocorticoid receptor has been implied to function as a suppressor of urothelial tumorigenesis. This article summarizes and discusses available data suggesting that steroid hormone receptors, including androgen receptor, estrogen receptor-α, estrogen receptor-β, glucocorticoid receptor, progesterone receptor and vitamin D receptor, as well as their related signals, contribute to modulating urothelial tumorigenesis.

scholarly journals A conserved mechanism of sirtuin signalling through steroid hormone receptors

2019 ◽  
Vol 39 (12) ◽  
Author(s):  
Henry K. Bayele
Keyword(s):  
Drug Targets ◽  
Metabolic Regulation ◽  
Hormone Receptors ◽  
Steroid Receptors ◽  
Steroid Hormone ◽  
Steroid Hormone Receptors ◽  
Nuclear Receptor Coregulators ◽  
Dafachronic Acid ◽  
Important Drug

Abstract SIRT1 and orthologous sirtuins regulate a universal mechanism of ageing and thus determine lifespan across taxa; however, the precise mechanism remains vexingly polemical. They also protect against many metabolic and ageing-related diseases by dynamically integrating several processes including autophagy, proteostasis, calorie restriction, circadian rhythmicity and metabolism. These sirtuins are therefore important drug targets particularly because they also transduce allosteric signals from sirtuin-activating compounds such as resveratrol into increased healthspan in evolutionarily diverse organisms. While many of these functions are apparently regulated by deacetylation, that mechanism may not be all-encompassing. Since gonadal signals have been shown to regulate ageing/lifespan in worms and flies, the present study hypothesized that these sirtuins may act as intermediary factors for steroid hormone signal transduction. Accordingly, SIRT1 and its orthologues, Sir2 and Sir-2.1, are shown to be veritable nuclear receptor coregulators that classically coactivate the oestrogen receptor in the absence of ligand; coactivation was further increased by 17β-oestradiol. Remarkably in response to the worm steroid hormone dafachronic acid, SIRT1 reciprocally coactivates DAF-12, the steroid receptor that regulates nematode lifespan. These results suggest that steroid hormones may co-opt and modulate a phyletically conserved mechanism of sirtuin signalling through steroid receptors. Hence, it is interesting to speculate that certain sirtuin functions including prolongevity and metabolic regulation may be mechanistically linked to this endocrine signalling pathway; this may also have implications for understanding the determinative role of gonadal steroids such as oestradiol in human ageing. At its simplest, this report shows evidence for a hitherto unknown deacetylation-independent mechanism of sirtuin signalling.

scholarly journals Isoform-Specific Transcriptional Regulation by Thyroid Hormone Receptors: Hormone-Independent Activation Operates through a Steroid Receptor Mode of Coactivator Interaction

2001 ◽  
Vol 15 (7) ◽  
pp. 1170-1185 ◽  
Author(s):  
Zhihong Yang ◽  
Martin L. Privalsky
Keyword(s):  
Thyroid Hormone ◽  
Transcriptional Activation ◽  
Hormone Receptors ◽  
Steroid Hormone ◽  
Expression Patterns ◽  
Steroid Receptor ◽  
Steroid Hormone Receptors ◽  
Thyroid Hormone Receptors ◽  
Interaction Domain ◽  
Specific Expression

Abstract Thyroid hormone receptors (T3Rs) are hormone-regulated transcription factors that play important roles in vertebrate homeostasis, differentiation, and development. T3Rs are synthesized as multiple isoforms that display tissue-specific expression patterns and distinct transcriptional properties. Most T3R isoforms associate with coactivator proteins and mediate transcriptional activation only in the presence of thyroid hormone. The pituitary-specific T3Rβ-2 isoform departs from this general rule and is able to interact with p160 coactivators, and to mediate transcriptional activation in both the absence and presence of hormone. We report here that this hormone-independent activation is mediated by contacts between the unique N terminus of T3Rβ-2 and an internal interaction domain in the SRC-1 (steroid receptor coactivator-1) and GRIP-1 (glucocorticoid receptor interacting protein 1) coactivators. These hormone-independent contacts between T3Rβ-2 and the p160 coactivators are distinct in sequence and function from the LXXLL motifs that mediate hormone-dependent transcriptional activation and resemble instead a mode of coactivator recruitment previously observed only for the steroid hormone receptors and only in the presence of steroid hormone. Our results suggest that the transcriptional properties of the different T3R isoforms represent a combinatorial mixture of repression, antirepression, and hormone-independent and hormone-dependent activation functions that operate in conjunction to determine the ultimate transcriptional outcome.

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