scholarly journals The Von Hippel-Lindau Protein Suppresses Androgen Receptor Activity

2014 ◽  
Vol 28 (2) ◽  
pp. 239-248 ◽  
Author(s):  
Jing Wang ◽  
Wei Zhang ◽  
Wei Ji ◽  
Xing Liu ◽  
Gang Ouyang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Physiological Role ◽  
Transcription Activity ◽  
Von Hippel Lindau ◽  
Prostate Cancer Development ◽  
Androgen Receptor Activity ◽  
Ubiquitin Proteasome ◽  
Proteasome Pathway

Abstract The androgen receptor (AR) plays a pivotal role in prostate homeostasis and prostate cancer development. To understand the mechanism underlying the regulation of the AR holds a promise for developing novel therapeutic approaches for prostate cancer. Here, we show that the Von Hippel-Lindau gene product, pVHL, physically interacts with AR and inhibits AR transcription activity but does not induce AR turnover. Moreover, pVHL also suppresses androgen-induced cell proliferation, implicating a physiological role of pVHL in androgen-induced signaling pathway. In addition, we provide evidence to show that pVHL actually enhanced AR de-ubiquitination instead of inducing AR ubiquitination, uncovering a noncanonical role of pVHL in the ubiquitin proteasome pathway. Our data reveal a novel function of pVHL in the regulation of AR transcription activity, which may expand the scope of pVHL in tumor suppression and provide mechanistic insight into prostate cancer initiation and progression.

scholarly journals Degradation and beyond: Control of androgen receptor activity by the proteasome system

2006 ◽  
Vol 11 (1) ◽  
Author(s):  
Tomasz Jaworski
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Critical Role ◽  
Ubiquitin Proteasome System ◽  
Cancer Therapies ◽  
The Family ◽  
Prostate Cancer Development ◽  
Androgen Receptor Activity ◽  
Ubiquitin Proteasome

AbstractThe androgen receptor (AR) is a transcription factor belonging to the family of nuclear receptors which mediates the action of androgens in the development of urogenital structures. AR expression is regulated post-translationally by the ubiquitin/proteasome system. This regulation involves more complex mechanisms than typical degradation. The ubiquitin/proteasome system may regulate AR via mechanisms that do not engage in receptor turnover. Given the critical role of AR in sexual development, this complex regulation is especially important. Deregulation of AR signalling may be a causal factor in prostate cancer development. AR is the main target in prostate cancer therapies. Due to the critical role of the ubiquitin/proteasome system in AR regulation, current research suggests that targeting AR degradation is a promising approach.

scholarly journals Eighty Years of Targeting Androgen Receptor Activity in Prostate Cancer: The Fight Goes on

Cancers ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 509
Author(s):  
Eva Estébanez-Perpiñá ◽  
Charlotte L. Bevan ◽  
Iain J. McEwan
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Metastatic Disease ◽  
Structural Information ◽  
The West ◽  
Seminal Paper ◽  
Common Cancer ◽  
Androgen Receptor Activity ◽  
Direct Target

Prostate cancer (PCa) is the most common cancer in men in the West, other than skin cancer, accounting for over a quarter of cancer diagnoses in US men. In a seminal paper from 1941, Huggins and Hodges demonstrated that prostate tumours and metastatic disease were sensitive to the presence or absence of androgenic hormones. The first hormonal therapy for PCa was thus castration. In the subsequent eighty years, targeting the androgen signalling axis, where possible using drugs rather than surgery, has been a mainstay in the treatment of advanced and metastatic disease. Androgens signal via the androgen receptor, a ligand-activated transcription factor, which is the direct target of many such drugs. In this review we discuss the role of the androgen receptor in PCa and how the combination of structural information and functional screenings is continuing to be used for the discovery of new drug to switch off the receptor or modify its function in cancer cells.

Wild‐type but not mutant androgen receptor inhibits expression of the hTERT telomerase subunit: a novel role of AR mutation for prostate cancer development

2007 ◽  
Vol 22 (4) ◽  
pp. 1258-1267 ◽  
Author(s):  
Udo Moehren ◽  
Maria Papaioannou ◽  
Christina A. Reeb ◽  
Annalisa Grasselli ◽  
Simona Nanni ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Cancer Development ◽  
Wild Type ◽  
Subunit A ◽  
Prostate Cancer Development

Role of molecular chaperones in steroid receptor action

2004 ◽  
Vol 40 ◽  
pp. 41-58 ◽  
Author(s):  
William B Pratt ◽  
Mario D Galigniana ◽  
Yoshihiro Morishima ◽  
Patrick J M Murphy
Keyword(s):  
Transcriptional Activation ◽  
Protein Trafficking ◽  
Steroid Receptors ◽  
Transcriptional Regulatory ◽  
Ubiquitin Proteasome ◽  
Proteasome Pathway ◽  
Receptor Action ◽  
Binding Cleft ◽  
Hsp 90

Unliganded steroid receptors are assembled into heterocomplexes with heat-shock protein (hsp) 90 by a multiprotein chaperone machinery. In addition to binding the receptors at the chaperone site, hsp90 binds cofactors at other sites that are part of the assembly machinery, as well as immunophilins that connect the assembled receptor-hsp90 heterocomplexes to a protein trafficking pathway. The hsp90-/hsp70-based chaperone machinery interacts with the unliganded glucocorticoid receptor to open the steroid-binding cleft to access by a steroid, and the machinery interacts in very dynamic fashion with the liganded, transformed receptor to facilitate its translocation along microtubular highways to the nucleus. In the nucleus, the chaperone machinery interacts with the receptor in transcriptional regulatory complexes after hormone dissociation to release the receptor and terminate transcriptional activation. By forming heterocomplexes with hsp90, the chaperone machinery stabilizes the receptor to degradation by the ubiquitin-proteasome pathway of proteolysis.

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