{"id":49430,"date":"2016-08-25T00:00:00","date_gmt":"2016-08-24T23:00:00","guid":{"rendered":"http:\/\/www.pcb.ub.edu\/researchers-at-irb-barcelona-discover-the-hidden-potential-of-disordered-proteins\/"},"modified":"2020-11-18T14:55:11","modified_gmt":"2020-11-18T13:55:11","slug":"researchers-at-irb-barcelona-discover-the-hidden-potential-of-disordered-proteins","status":"publish","type":"post","link":"https:\/\/www.pcb.ub.edu\/en\/researchers-at-irb-barcelona-discover-the-hidden-potential-of-disordered-proteins\/","title":{"rendered":"Researchers at IRB Barcelona discover the hidden potential of disordered proteins"},"content":{"rendered":"<p>Published in the journalACS Chemical Biology\u00a0(<a href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/27356095\" target=\"_blank\" rel=\"noopener noreferrer\">doi:\u00a010.1021\/acschembio.6b00182<\/a>),\u00a0the results pave the way towards identifying new therapeutic targets for many diseases.<\/p>\n<p>Xavier Salvatella, ICREA researcher and head of the\u00a0<a href=\"http:\/\/www.irbbarcelona.org\/en\/research\/laboratory-of-molecular-biophysics\" target=\"_blank\" rel=\"noopener noreferrer\">Molecular Biophysics lab<\/a>, studies the structure and function of the Androgen Receptor (AR), a protein involved in prostate cancer. Although a slow-growing cancer and with good prognosis (about 70% of patients are cured with surgery), there are many cases in which the cancer cells spread throughout the body. This stage of the disease is commonly addressed by preventing the activation of AR, thereby causing cancer cells to die. However, tumours adapt by becoming resistant to treatments, and currently there are no other treatment options.<\/p>\n<p>\u201cThis protein is chameleonic,\u201d explains Salvatella. \u201cInstead of being rigid, it\u2019s highly flexible and dynamic, and these properties allow it to take on many forms.\u201d The AR is a protein that carries out its activity in the cell nucleus, where it regulates gene expression. It has a structured region, which binds to DNA, and an intrinsically disordered region, that is to say without structure. \u201cWe know that the disordered region is crucial for the activity of this protein. However, because of the absence of its three-dimensional structure, it was ruled out as a drug target.\u201d<\/p>\n<p>Through high-resolution molecular analysis, the researchers, including\u00a0Eva de Mol, former &#8220;la Caixa&#8221; PhD student at IRB Barcelona and first author of the study, discovered that there is a certain degree of structure within the disordered region. \u201cIn its natural context, bound to DNA in the cell nucleus, it\u2019s possible that this protein is highly structured, even possibly resembling a conventional therapeutic target,\u201d says Salvatella.<\/p>\n<p>Furthermore, the scientists have observed that\u00a0an experimental drug against prostate cancer binds to this region. \u201cIt\u2019s an important finding because it opens up a whole series of possibilities to reconsider the discovery of drug targets that had previously been ruled out,\u201d says the researcher.<\/p>\n<p>Salvatella is optimistic about the relevance of the findings. \u201cThese disordered proteins are crucial in the development of Alzheimer\u2019s and Parkinson\u2019s disease, for example. What we need to do now is to apply this knowledge and begin a systematic search for drugs.\u201d The lab will begin drug screening within two years. \u201cIt\u2019ll be difficult to identify drugs that specifically target these regions, but I think it\u2019s achievable and worth the effort.\u201d<\/p>\n<p>This work was supported by the Ministry of Economy and Competitiveness and European Regional Development Funds &#8211; ERDF (Government of Spain),\u00a0La Marat\u00f3\u00a0de TV3, CancerTec programme from \u201cla Caixa\u201d, the European Research Council (ERC) and the Government of Catalonia.<\/p>\n<p>\u00a0<\/p>\n<p>\u2022\u00a0<strong>Reference article:<\/strong>\u00a0Eva De Mol, R. Bryn Fenwick, Christopher T. W. Phang, Victor Buz\u00f3n, Elzbieta Szulc, Alex de la Fuente, Albert Escobedo, Jes\u00fas Garc\u00eda, Carlos W. Bertoncini, Eva Est\u00e9banez-Perpi\u00f1\u00e1, Iain J. McEwan, Antoni Riera and Xavier Salvatella. &#8220;<a href=\"http:\/\/pubs.acs.org\/doi\/abs\/10.1021\/acschembio.6b00182\" target=\"_blank\" rel=\"noopener noreferrer\">EPI-001, A Compound Active against Castration-Resistant Prostate Cancer, Targets Transactivation Unit 5 of the Androgen Receptor<\/a>&#8220;. ACS Chemical Biology\u00a0(2016) doi:\u00a010.1021\/acschembio.6b00182\u00a0<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Prostate cancer, Alzheimer\u2019s, Parkinson\u2019s&#8230;these three diseases are associated with proteins that share a common feature, namely disordered regions that have no apparent rigid three-dimensional structure. In spite of the potential of these regions as therapeutic targets, it was believed that drugs could not be directed to them. But now scientists at the <a href=\"http:\/\/www.pcb.ub.edu\/portal\/en\/cerca?p_p_id=cercador_WAR_empleatsempresesportlet&amp;p_p_lifecycle=0&amp;p_p_state=maximized&amp;p_p_mode=view&amp;p_p_col_id=column-1&amp;p_p_col_count=1&amp;_cercador_WAR_empleatsempresesportlet_jspPage=%2Fhtml%2Fcommon%2Fdetall-empresa.jsp&amp;_cercador_WAR_empleatsempresesportlet_empresaId=ENT_000001&amp;_cercador_WAR_empleatsempresesportlet_redirect=%2Fportal%2Fca%2Fcerca%3Fp_p_id%3Dcercador_WAR_empleatsempresesportlet%26p_p_lifecycle%3D0%26p_p_mode%3Dview%26_cercador_WAR_empleatsempresesportlet_keywords%3Dirb%26_cercador_WAR_empleatsempresesportlet_tab%3D1\" target=\"_blank\" rel=\"noopener noreferrer\">Institute for Research in Biomedicine (IRB Barcelona)<\/a>, based at the Barcelona Science Park (PCB), have rediscovered their utility as drug targets.\u00a0<\/p>\n<p>\u00a0<\/p>\n","protected":false},"author":1,"featured_media":52898,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"inline_featured_image":false,"footnotes":""},"categories":[8],"tags":[],"class_list":["post-49430","post","type-post","status-publish","format-standard","has-post-thumbnail","category-uncategorized"],"acf":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v27.3 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>Researchers at IRB Barcelona discover the hidden potential of disordered proteins - Parc Cient\u00edfic de Barcelona<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/www.pcb.ub.edu\/en\/researchers-at-irb-barcelona-discover-the-hidden-potential-of-disordered-proteins\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Researchers at IRB Barcelona discover the hidden potential of disordered proteins - Parc Cient\u00edfic de Barcelona\" \/>\n<meta property=\"og:description\" content=\"Prostate cancer, Alzheimer\u2019s, Parkinson\u2019s...these three diseases are associated with proteins that share a common feature, namely disordered regions that have no apparent rigid three-dimensional structure. In spite of the potential of these regions as therapeutic targets, it was believed that drugs could not be directed to them. But now scientists at the Institute for Research in Biomedicine (IRB Barcelona), based at the Barcelona Science Park (PCB), have rediscovered their utility as drug targets.\u00a0 \u00a0\" \/>\n<meta property=\"og:url\" content=\"https:\/\/www.pcb.ub.edu\/en\/researchers-at-irb-barcelona-discover-the-hidden-potential-of-disordered-proteins\/\" \/>\n<meta property=\"og:site_name\" content=\"Parc Cient\u00edfic de Barcelona\" \/>\n<meta property=\"article:published_time\" content=\"2016-08-24T23:00:00+00:00\" \/>\n<meta property=\"article:modified_time\" content=\"2020-11-18T13:55:11+00:00\" \/>\n<meta property=\"og:image\" content=\"https:\/\/www.pcb.ub.edu\/wp-content\/uploads\/2016\/08\/16057065075fb5230b748f8.jpeg\" \/>\n\t<meta property=\"og:image:width\" content=\"800\" \/>\n\t<meta property=\"og:image:height\" content=\"257\" \/>\n\t<meta property=\"og:image:type\" content=\"image\/jpeg\" \/>\n<meta name=\"author\" content=\"adminpcb\" \/>\n<meta name=\"twitter:card\" content=\"summary_large_image\" \/>\n<meta name=\"twitter:label1\" content=\"Written by\" \/>\n\t<meta name=\"twitter:data1\" content=\"adminpcb\" \/>\n\t<meta name=\"twitter:label2\" content=\"Est. reading time\" \/>\n\t<meta name=\"twitter:data2\" content=\"2 minutes\" \/>\n<script type=\"application\/ld+json\" class=\"yoast-schema-graph\">{\"@context\":\"https:\\\/\\\/schema.org\",\"@graph\":[{\"@type\":\"Article\",\"@id\":\"https:\\\/\\\/www.pcb.ub.edu\\\/en\\\/researchers-at-irb-barcelona-discover-the-hidden-potential-of-disordered-proteins\\\/#article\",\"isPartOf\":{\"@id\":\"https:\\\/\\\/www.pcb.ub.edu\\\/en\\\/researchers-at-irb-barcelona-discover-the-hidden-potential-of-disordered-proteins\\\/\"},\"author\":{\"name\":\"adminpcb\",\"@id\":\"https:\\\/\\\/www.pcb.ub.edu\\\/es\\\/#\\\/schema\\\/person\\\/d13cab05cd0a75b17fddca8496481021\"},\"headline\":\"Researchers at IRB Barcelona discover the hidden potential of disordered proteins\",\"datePublished\":\"2016-08-24T23:00:00+00:00\",\"dateModified\":\"2020-11-18T13:55:11+00:00\",\"mainEntityOfPage\":{\"@id\":\"https:\\\/\\\/www.pcb.ub.edu\\\/en\\\/researchers-at-irb-barcelona-discover-the-hidden-potential-of-disordered-proteins\\\/\"},\"wordCount\":509,\"image\":{\"@id\":\"https:\\\/\\\/www.pcb.ub.edu\\\/en\\\/researchers-at-irb-barcelona-discover-the-hidden-potential-of-disordered-proteins\\\/#primaryimage\"},\"thumbnailUrl\":\"https:\\\/\\\/www.pcb.ub.edu\\\/wp-content\\\/uploads\\\/2016\\\/08\\\/16057065075fb5230b748f8.jpeg\",\"inLanguage\":\"en-US\"},{\"@type\":\"WebPage\",\"@id\":\"https:\\\/\\\/www.pcb.ub.edu\\\/en\\\/researchers-at-irb-barcelona-discover-the-hidden-potential-of-disordered-proteins\\\/\",\"url\":\"https:\\\/\\\/www.pcb.ub.edu\\\/en\\\/researchers-at-irb-barcelona-discover-the-hidden-potential-of-disordered-proteins\\\/\",\"name\":\"Researchers at IRB Barcelona discover the hidden potential of disordered proteins - 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