{"id":22272,"date":"2023-03-17T08:30:45","date_gmt":"2023-03-17T07:30:45","guid":{"rendered":"https:\/\/idibell.cat\/en\/?p=22272"},"modified":"2023-03-17T08:59:00","modified_gmt":"2023-03-17T07:59:00","slug":"study-describes-the-structural-and-functional-effects-of-several-mutations-on-the-androgen-receptor","status":"publish","type":"post","link":"https:\/\/idibell.cat\/en\/2023\/03\/study-describes-the-structural-and-functional-effects-of-several-mutations-on-the-androgen-receptor\/","title":{"rendered":"Study describes the structural and functional effects of several mutations on the androgen receptor"},"content":{"rendered":"<p>The androgen receptor is a key transcriptional factor for the proper sex development \u2014specially in males\u2014 and the physiological balance of all the tissues that express this receptor. The androgen receptor is involved in several pathologies and syndromes, such as the spinal and bulbar muscular atrophy or androgen insensitivity syndrome, among others, for which there is no specific treatment. Regarded as the main initial and progression factor in prostate cancer \u2014the second most common malignant disease in men in industrialized countries\u2014, this receptor has been, for decades, the main therapeutical target for the treatment against this disease.<\/p>\n<p>Now, a study published in the prestigious journal <a href=\"https:\/\/www.science.org\/doi\/10.1126\/sciadv.ade2175\"><em>Science Advances<\/em><\/a> describes the structural and functional effects of mutations on the androgen receptor, as well as how these changes lead to the development of prostate cancer. The study is led by lecturer Eva Est\u00e9banez-Perpi\u00f1\u00e1, from the Department of Biochemistry and Molecular Biomedicine of the Faculty of Biology and from the Institute of Biomedicine of the University of Barcelona (IBUB) \u2014with headquarters at the Barcelona Science Park (PCB)\u2014, in collaboration with the experts Pablo Fuentes-Prior, former head of a research group at the Research Institute of Sant Pau (IBB Sannt Pau), and \u00c1lvaro Ayt\u00e9s, from the Bellvitge Biomedical Research Institute (IDIBELL) and the Catalan Institute of Oncology (ICO).<\/p>\n<p>The study, whose first coauthors are Andrea Alegre and Alba Jim\u00e9nez (UB-IBUB) and Adri\u00e1n Mart\u00ednez (ICO and IDIBELL), includes the participation of the team led by lecturer Jaime Rubio Mart\u00ednez, from the Faculty of Chemistry and the UB Institute of Theoretical and Computational Chemistry (IQTC), and groups from CSIC and the National Institute of Health and MedicalResearch in France (INSERM).<\/p>\n<p>&nbsp;<\/p>\n<h3>Point mutations in the androgen receptor<\/h3>\n<p>&nbsp;<\/p>\n<p>The human androgen receptor is a key protein in the development and functioning of the prostate in response to male hormones, such as testosterone. Point mutations in the androgen receptor \u2014specifically, one aminoacid changing for another\u2014 are one of the main mechanisms than can lead to structural and functional alterations in the receptor, which result in the development of diseases.<\/p>\n<p>The results of the study show that the analysed mutations affect several functional regions of the union domain of the androgen receptor to testosterone. In particular, these are mutations that alter a region of the receptor which is the target for posttranscriptional modifications (that is, modifications in the protein once this is produced).<\/p>\n<p>This type of chemical alterations affect specific amino acids of the androgen receptor and are executed by regulating proteins which are decisive for the proper functioning of the receptor. If this receptor\u2019s regulation pathway is altered \u2014such as the case of the presence of mutations described by the team\u2014, its function is deregulated and it can be dysfunctional and cause pathologies.<\/p>\n<p>\u201cIn our study, we experimentally checked that these mutations deregulate a specific mutation, known as <em>arginine methylation<\/em>, which is one of the posttranscriptional modifications, due to the structural changes these alterations produce in a functional area of the receptor. Also, we could observe that the deregulation of the androgen receptor methylation involves relevant changes in its function within the cell\u201d, the team concludes.<\/p>\n<p>&nbsp;<\/p>\n<p>&nbsp;<\/p>\n<p><em>The Bellvitge Biomedical Research Institute (IDIBELL) is a biomedical research center created in 2004. It is participated by the Bellvitge University Hospital and the Viladecans Hospital of the Catalan Institute of Health, the Catalan Institute of Oncology, the University of Barcelona and the City Council of L&#8217;Hospitalet de Llobregat.<\/em><\/p>\n<p><em>IDIBELL is a member of the Campus of International Excellence of the University of Barcelona HUBc and is part of the CERCA institution of the Generalitat de Catalunya. In 2009 it became one of the first five Spanish research centers accredited as a health research institute by the Carlos III Health Institute. In addition, it is part of the &#8220;HR Excellence in Research&#8221; program of the European Union and is a member of EATRIS and REGIC. Since 2018, IDIBELL has been an Accredited Center of the AECC Scientific Foundation (FCAECC).<\/em><\/p>\n","protected":false},"excerpt":{"rendered":"<p>The androgen receptor is the main target in the fight against prostate cancer. The study, published in the journal Science Advances, states that the analyzed mutations affect several functional regions of the union domain of the androgen receptor to testosterone.<\/p>\n","protected":false},"author":8,"featured_media":22273,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"site-sidebar-layout":"default","site-content-layout":"default","ast-site-content-layout":"","site-content-style":"default","site-sidebar-style":"default","ast-global-header-display":"","ast-banner-title-visibility":"","ast-main-header-display":"","ast-hfb-above-header-display":"","ast-hfb-below-header-display":"","ast-hfb-mobile-header-display":"","site-post-title":"","ast-breadcrumbs-content":"","ast-featured-img":"","footer-sml-layout":"","theme-transparent-header-meta":"default","adv-header-id-meta":"","stick-header-meta":"default","header-above-stick-meta":"","header-main-stick-meta":"","header-below-stick-meta":"","astra-migrate-meta-layouts":"default","ast-page-background-enabled":"default","ast-page-background-meta":{"desktop":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"tablet":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"mobile":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""}},"ast-content-background-meta":{"desktop":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"tablet":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"mobile":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""}},"footnotes":""},"categories":[180,264,190],"tags":[],"class_list":["post-22272","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-cancer","category-molecular-mechanisms-and-experimental-therapy-in-oncology-program-oncobell","category-resistance-and-progression-mechanisms-in-prostate-cancer"],"publishpress_future_action":{"enabled":false,"date":"2024-12-31 00:50:04","action":"change-status","newStatus":"draft","terms":[],"taxonomy":"category"},"publishpress_future_workflow_manual_trigger":{"enabledWorkflows":[]},"_links":{"self":[{"href":"https:\/\/idibell.cat\/en\/wp-json\/wp\/v2\/posts\/22272","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/idibell.cat\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/idibell.cat\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/idibell.cat\/en\/wp-json\/wp\/v2\/users\/8"}],"replies":[{"embeddable":true,"href":"https:\/\/idibell.cat\/en\/wp-json\/wp\/v2\/comments?post=22272"}],"version-history":[{"count":1,"href":"https:\/\/idibell.cat\/en\/wp-json\/wp\/v2\/posts\/22272\/revisions"}],"predecessor-version":[{"id":22274,"href":"https:\/\/idibell.cat\/en\/wp-json\/wp\/v2\/posts\/22272\/revisions\/22274"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/idibell.cat\/en\/wp-json\/wp\/v2\/media\/22273"}],"wp:attachment":[{"href":"https:\/\/idibell.cat\/en\/wp-json\/wp\/v2\/media?parent=22272"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/idibell.cat\/en\/wp-json\/wp\/v2\/categories?post=22272"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/idibell.cat\/en\/wp-json\/wp\/v2\/tags?post=22272"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}