An Sp1 Modulated Regulatory Region Unique to Higher Primates Regulates Human Androgen Receptor Promoter Activity in Prostate Cancer Cells

Funding: This work was supported by the Chief Scientist’s Office (CSO) of the Scottish Government (http://www.cso.scot.nhs.uk/): CWH (CZB-4-477) and IH (ETM/382).Peer reviewedPublisher PD

Nuclear hormone receptor architecture - form and dynamics: The 2009 FASEB Summer Conference on Dynamic Structure of the Nuclear Hormone Receptors

Nuclear hormone receptors (NHRs) represent a large and diverse family of ligand-activated transcription factors involved in regulating development, metabolic homeostasis, salt balance and reproductive health. The ligands for these receptors are typically small hydrophobic molecules such as steroid hormones, thyroid hormone, vitamin D3 and fatty acid derivatives. The first NHR structural information appeared ~20 years ago with the solution and crystal structures of the DNA binding domains and was followed by the structure of the agonist and antagonist bound ligand binding domains of different NHR members. Interestingly, in addition to these defined structural features, it has become clear that NHRs also possess significant structural plasticity. Thus, the dynamic structure of the NHRs was the topic of a recent stimulating and informative FASEB Summer Research Conference held in Vermont

Negative regulation of the androgen receptor gene through a primate specific androgen response element present in the 5' UTR

Open Access This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited. Acknowledgements This work was supported by funding from the Chief Scientist Office, Government of Scotland (Grant Nos CZB/4/477 and ETM/258). DNL was supported by the Association for International Cancer Research (Grant No. 03–127)Peer reviewedPublisher PD

Eighty years of targeting androgen receptor activity in prostate cancer: the fight goes on

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

Natural disordered sequences in the amino terminal domain of nuclear receptors: lessons from the androgen and glucocorticoid receptors

Steroid hormones are a diverse class of structurally related molecules, derived from cholesterol, that include androgens, estrogens, progesterone and corticosteroids. They represent an important group of physiologically active signalling molecules that bind intracellular receptor proteins and regulate genes involved in developmental, reproductive and metabolic processes. The receptor proteins share structurally and functionally related ligand binding and DNA-binding domains, but possess distinct N-terminal domains (NTD) of unique length and amino acids sequence. The NTD contains sequences important for gene regulation, exhibit structure plasticity and are likely to contribute to the specificity of the steroid hormone/receptor response

Functional effects of polymorphisms on glucocorticoid receptor modulation of human anxiogenic substance-P gene promoter activity in primary amygdala neurones

This work was funded by The BBSRC (BB/D004659/1) the Wellcome Trust (080980/Z/06/Z) and the Medical Research Council (G0701003). Colin Hay was funded by the Chief Scientist Office, Scotland. Scott Davidson was funded by a BBSRC strategic studentship (BBS/S/2005/12001). Philip Cowie was funded by the Scottish Universities Life Sciences Alliance (SULCA).Peer reviewedPublisher PD

Tissue control of androgen action : The ups and downs of androgen receptor expression

Work in the McEwan Laboratory is funded by the Chief Scientist Office of Scottish Government: Grants ETM-258 and ETM-382. BE is supported by an Erasmus scholarship.Peer reviewedPostprin

EPI-001, A Compound Active against Castration-Resistant Prostate Cancer, Targets Transactivation Unit 5 of the Androgen Receptor

ACKNOWLEDGEMENTS We thank J. M. Valverde (IRB) as well as the NMR facilities of the University of Barcelona (CCiT UB) and the Instituto de Química Física Rocasolano (IQFR, CSIC) for their assistance in, respectively, protein production and NMR. This work was supported by IRB, ICREA (X.S.), Obra Social “la Caixa” (Fellowship to E.D.M. and CancerTec grants to X.S.) MICINN (CTQ2009-08850 to X.S.), MINECO (BIO2012-31043 to X.S.; CTQ2014-56361-P to A.R), Marató de TV3 (102030 to X.S. and 102031 to E.E.P) the COFUND programme of the European Commission (C.T.W.P., A. R. and X.S.), the European Research Council (CONCERT, contract number 648201, to X.S.), the Ramón y Cajal program of MICINN (RYC-2011-07873 to C.W.B.) the Serra Hunter Programme (E.E.P.) and AGAUR (SGR-2014-56RR14 to E.E.P). IRB Barcelona is the recipient of a Severo Ochoa Award of Excellence from MINECO (Government of Spain)Peer reviewedPostprin

Topological dynamics of an intrinsically disordered N-terminal domain of the human androgen receptor

ACKNOWLEDGEMENTS We are thankful to Eugene Shakhnovich (Harvard University) for critical reading of the manuscript, and to Peter Bolhuis and Ioana Ilie (University of Amsterdam) for technical discussions. The research in Mashaghi lab is supported by funding from Muscular Dystrophy Association (USA), Grant Number MDA628071, and Dutch Research Council (Nederlandse Organisatie voor Wetenschappelijk Onderzoek) through NWA-IDG (NWA.1228.192.309) and Open Competition XS (OCENW.XS.076).Peer reviewedPublisher PD

Targeting androgen receptor activation function-1 with EPI to overcome resistance mechanisms in castration-resistant prostate cancer

Acknowledgments The authors thank Kate Watt (University of Aberdeen, Aberdeen, Scotland) for technical support. The authors are also grateful to Country Meadows Senior Men's Golf Charity Classic for financial support of this research. Financial support: This research was supported by grants to MDS from the NCI (2R01CA105304), the Canadian Institutes of Health Research (MOP79308) and the US Army Medical Research and Materiel Command Prostate Cancer Research Program (E81XWH-11-1-0551). Research by IJM’s group was supported by the Chief Scientist’s Office of the Scottish Government (ETM-258 and -382). We are grateful to Country Meadows Senior Men’s Golf Charity Classic for financial support of this research.Peer reviewedPostprin