{"id":23345,"date":"2023-03-17T08:30:45","date_gmt":"2023-03-17T07:30:45","guid":{"rendered":"https:\/\/idibell.cat\/?p=23345"},"modified":"2023-03-17T08:57:52","modified_gmt":"2023-03-17T07:57:52","slug":"un-treball-descriu-els-efectes-estructurals-i-funcionals-de-diverses-mutacions-sobre-el-receptor-dandrogens","status":"publish","type":"post","link":"https:\/\/idibell.cat\/2023\/03\/un-treball-descriu-els-efectes-estructurals-i-funcionals-de-diverses-mutacions-sobre-el-receptor-dandrogens\/","title":{"rendered":"Un treball descriu els efectes estructurals i funcionals de diverses mutacions sobre el receptor d\u2019andr\u00f2gens"},"content":{"rendered":"

El receptor d\u2019andr\u00f2gens \u00e9s un factor de transcripci\u00f3 clau per al desenvolupament correcte de les caracter\u00edstiques sexuals \u2014en especial, les masculines\u2014 i per a l\u2019equilibri fisiol\u00f2gic de tots els teixits que expressen aquest receptor. Aquest receptor est\u00e0 implicat en diverses patologies i s\u00edndromes \u2014l\u2019atr\u00f2fia muscular espinal i bulbar o la s\u00edndrome d\u2019insensibilitat als andr\u00f2gens, entre d\u2019altres\u2014, per a les quals encara no hi ha un tractament definitiu. Considerat com el principal factor d\u2019inici i de progressi\u00f3 del c\u00e0ncer de pr\u00f2stata \u2014la segona malaltia maligna m\u00e9s comuna en homes en pa\u00efsos industrialitzats\u2014, aquest receptor constitueix des de fa d\u00e8cades la principal diana terap\u00e8utica per al tractament d\u2019aquesta malaltia.<\/p>\n

Ara, un estudi publicat a la revista Science Advances<\/em><\/a> descriu els efectes estructurals i\u00a0 funcionals de diverses mutacions en el receptor d\u2019andr\u00f2gens, i com aquests canvis\u00a0 condueixen al desenvolupament del c\u00e0ncer de pr\u00f2stata. Lidera el treball la professora Eva Est\u00e9banez-Perpi\u00f1\u00e1, del Departament de Bioqu\u00edmica i Biomedicina Molecular de la Facultat de Biologia i de l\u2019Institut de Biomedicina de la Universitat de Barcelona (IBUB) \u2014amb seu al Parc Cient\u00edfic de Barcelona (PCB)\u2014, en col\u00b7laboraci\u00f3 amb Pablo Fuentes-Prior, antic cap de grup a l\u2019Institut de Recerca de l\u2019Hospital de la Santa Creu i Sant Pau (IIB Sant Pau), i \u00c1lvaro Ayt\u00e9s, de l\u2019Institut d\u2019Investigaci\u00f3 Biom\u00e8dica de Bellvitge (IDIBELL) i l\u2019Institut Catal\u00e0 d\u2019Oncologia (ICO).<\/p>\n

En el treball, que t\u00e9 com a primers coautors Andrea Alegre i Alba Jim\u00e9nez (UB-IBUB) i Adri\u00e1n Mart\u00ednez (ICO i IDIBELL), tamb\u00e9 hi participen l\u2019equip del professor Jaime Rubio Mart\u00ednez, de la Facultat de Qu\u00edmica i l\u2019Institut de Qu\u00edmica Te\u00f2rica i Computacional (IQTC) de la UB, a m\u00e9s de grups del Consell Superior d\u2019Investigacions Cient\u00edfiques (CSIC) i de l\u2019Institut Nacional d\u2019Investigaci\u00f3 Recerca en Salut i Medicina de Fran\u00e7a (INSERM).<\/p>\n

 <\/p>\n

Mutacions puntuals en el receptor androg\u00e8nic<\/h3>\n

 <\/p>\n

El receptor hum\u00e0 d\u2019andr\u00f2gens \u00e9s una prote\u00efna clau en el desenvolupament i funcionament normal de la pr\u00f2stata en resposta a hormones masculines com ara la testosterona. Les mutacions puntuals en el receptor d\u2019andr\u00f2gens \u2014en concret, el canvi d\u2019un amino\u00e0cid per un altre\u2014 s\u00f3n un dels principals mecanismes que poden desencadenar alteracions estructurals i funcionals en el receptor que finalment donin lloc al desenvolupament de malalties.<\/p>\n

Els resultats del treball indiquen que les mutacions analitzades afecten diverses regions funcionals del domini d\u2019uni\u00f3 del receptor d\u2019andr\u00f2gens a la testosterona. En particular, es tracta de mutacions que alteren de manera decisiva una regi\u00f3 del receptor que \u00e9s diana de modificacions posttranscripcionals (\u00e9s a dir, modificacions de la prote\u00efna un cop ja ha estat produ\u00efda).<\/p>\n

Aquest tipus d\u2019alteracions qu\u00edmiques afecten amino\u00e0cids espec\u00edfics del receptor d\u2019andr\u00f2gens i s\u00f3n executades per prote\u00efnes reguladores que s\u00f3n decisives per al funcionament correcte del receptor. Si aquesta via de regulaci\u00f3 del receptor es veu alterada \u2014com ara quan s\u2019esdevenen les mutacions descrites per l\u2019equip\u2014, la seva funci\u00f3 es desregula i pot arribar a ser disfuncional i originar patologies.<\/p>\n

\u00abEn el nostre treball, hem comprovat experimentalment que aquestes mutacions desregulen una modificaci\u00f3 concreta \u2014coneguda com metilaci\u00f3 d\u2019arginines, <\/em>que \u00e9s un dels tipus de modificacions posttranscripcionals\u2014, degut al canvi estructural que aquestes alteracions produeixen en una \u00e0rea funcional del receptor. Aix\u00ed mateix, hem pogut provar que la desregulaci\u00f3 de la metilaci\u00f3 del receptor d\u2019andr\u00f2gens tamb\u00e9 comporta canvis rellevants en la seva funci\u00f3 dins la c\u00e8l\u00b7lula\u00bb, clou l\u2019equip investigador.<\/p>\n

 <\/p>\n

 <\/p>\n

L\u2019Institut d’Investigaci\u00f3 Biom\u00e8dica de Bellvitge (IDIBELL) \u00e9s un centre de recerca en biomedicina creat l\u2019any 2004. Est\u00e0 participat per l’Hospital Universitari de Bellvitge i l\u2019Hospital de Viladecans de l’Institut Catal\u00e0 de la Salut, l’Institut Catal\u00e0 d’Oncologia, la Universitat de Barcelona i l\u2019Ajuntament de l\u2019Hospitalet de Llobregat.<\/em><\/p>\n

L\u2019IDIBELL \u00e9s membre del Campus d’Excel\u00b7l\u00e8ncia Internacional de la Universitat de Barcelona HUBc i forma part de la instituci\u00f3 CERCA de la Generalitat de Catalunya. L’any 2009 es va convertir en un dels cinc primers centres d\u2019investigaci\u00f3 espanyols acreditats com a institut d\u2019investigaci\u00f3 sanit\u00e0ria per l\u2019Instituto de Salud Carlos III. A m\u00e9s, forma part del programa \u201cHR Excellence in Research\u201d de la Uni\u00f3 Europea i \u00e9s membre de EATRIS i REGIC. Des de l\u2019any 2018, l\u2019IDIBELL \u00e9s un Centro Acreditado de la Fundaci\u00f3n Cient\u00edfica AECC (FCAECC).<\/em><\/p>\n","protected":false},"excerpt":{"rendered":"

El receptor androg\u00e8nic \u00e9s la diana central de la lluita contra el c\u00e0ncer de pr\u00f2stata. El treball, publicat a la revista Science Advances, indica que les mutacions analitzades afecten diverses regions funcionals del domini d\u2019uni\u00f3 del receptor d\u2019andr\u00f2gens a la testosterona<\/p>\n","protected":false},"author":8,"featured_media":23346,"comment_status":"closed","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-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-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-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-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-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-gradient":""}},"footnotes":""},"categories":[332,395,447,452],"tags":[],"publishpress_future_action":{"enabled":false,"date":"2024-05-11 02:34:53","action":"change-status","newStatus":"draft","terms":[],"taxonomy":"category"},"_links":{"self":[{"href":"https:\/\/idibell.cat\/wp-json\/wp\/v2\/posts\/23345"}],"collection":[{"href":"https:\/\/idibell.cat\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/idibell.cat\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/idibell.cat\/wp-json\/wp\/v2\/users\/8"}],"replies":[{"embeddable":true,"href":"https:\/\/idibell.cat\/wp-json\/wp\/v2\/comments?post=23345"}],"version-history":[{"count":1,"href":"https:\/\/idibell.cat\/wp-json\/wp\/v2\/posts\/23345\/revisions"}],"predecessor-version":[{"id":23350,"href":"https:\/\/idibell.cat\/wp-json\/wp\/v2\/posts\/23345\/revisions\/23350"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/idibell.cat\/wp-json\/wp\/v2\/media\/23346"}],"wp:attachment":[{"href":"https:\/\/idibell.cat\/wp-json\/wp\/v2\/media?parent=23345"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/idibell.cat\/wp-json\/wp\/v2\/categories?post=23345"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/idibell.cat\/wp-json\/wp\/v2\/tags?post=23345"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}