{"id":25030,"date":"2013-08-11T12:49:00","date_gmt":"2013-08-11T10:49:00","guid":{"rendered":"https:\/\/www.embl.org\/news\/?p=25030"},"modified":"2024-03-26T00:29:29","modified_gmt":"2024-03-25T23:29:29","slug":"from-fireman-to-arsonist","status":"publish","type":"post","link":"https:\/\/www.embl.org\/news\/science\/from-fireman-to-arsonist\/","title":{"rendered":"From fireman to arsonist"},"content":{"rendered":"\n<div\n\n  \n  \n  class=\"vf-box\">\n  <h3 class=\"vf-box__heading\">In a nutshell:<\/h3>\n  <p class=\"vf-box__text\">&#8211; Tumour-suppressor protein p300 can turn into an oncogene<br \/>&#8211; Discovered through first 3D structure of protein\u2019s active core<br \/>&#8211; Means the protein could be a viable drug target<\/p>\n<\/div>\n\n\n\n<p>Like a fireman who becomes an arsonist, a protein that prevents cells becoming cancerous can also cause tumours, scientists at the European Molecular Biology Laboratory (EMBL) in Grenoble, France, have discovered. The finding, published today in&nbsp;<em>Nature Structural and Molecular Biology<\/em>, stems from the first 3D structure of the protein\u2019s active core, and opens up new avenues for drug design.<\/p>\n\n\n\n<p>\u201cEverybody thought this protein was a tumour-suppressor,\u201d says Daniel Panne, who led the work, \u201cbut we\u2019ve found that some mutations make it an oncogene \u2013 a gene that turns the cell cancerous \u2013 which actually makes it a viable drug target.\u201d&nbsp;<\/p>\n\n\n\n<p>Surprisingly, the finding reveals that mutations to this protein that have been linked to cancer can act in two different ways. As expected, some mutations make this \u2018fireman\u2019 protein \u2013 known as p300 \u2013 unable to put out the fire: they cause it to malfunction and lose control over other genes, thwarting its tumour-suppressor role. But, as Panne and colleagues discovered, some cancer-linked mutations actually make p300 into an arsonist: they make it hyperactive, turning it into an oncogene. Which mutations are which? The secret lies in an unexpected piece of the puzzle.<\/p>\n\n\n\n<p>In this study, Panne and colleagues determined the structure of the whole of the protein\u2019s active core \u2013 the part that physically interacts with genetic material to control genes \u2013 for the first time. They found that this 3D puzzle had one more piece than expected. p300 has a groove that it uses to slot onto the cell\u2019s genetic material to activate or inactivate genes, and the EMBL scientists found that, sitting on top of that groove like a lid, was a piece no-one knew this protein had. This \u2018lid\u2019 is like a built-in self-control mechanism. It determines whether the protein can slot onto genetic material or not: for p300 to do its job, it has to open the lid. But if a mutation interferes with the lid, keeping it permanently open, the protein will go into over-drive, and the resulting uncontrolled gene activity can lead to cancer.<\/p>\n\n\n\n<p>Tumours caused by these hyper-activating mutations could potentially be fought by drugs that inhibit p300. So, armed with the knowledge of the protein\u2019s structure, the EMBL scientists now plan to investigate how to thwart p300 when it goes from fireman to arsonist.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Like a fireman who becomes an arsonist, a protein that prevents cells becoming cancerous can also cause tumours, scientists at the European Molecular Biology Laboratory (EMBL) in Grenoble, France, have discovered. The finding, published today in&nbsp;Nature Structural and Molecular Biology, stems&hellip;<\/p>\n","protected":false},"author":16,"featured_media":25032,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[2,17591],"tags":[38,981,616,653],"embl_taxonomy":[],"class_list":["post-25030","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-science","category-science-technology","tag-cancer","tag-drug","tag-protein","tag-tumour"],"acf":{"show_featured_image":false,"vf_locked":false,"featured":false,"article_intro":"<p>Secret life of a cancer-related protein revealed by 3D structure<\/p>\n","article_sources":[{"source_description":"<p>Delvecchio, M., Gaucher, J., Aguilar-Gurrieri, C., Ortega, E. &#038; Panne, D. Structure of the catalytic core of p300 and implications for chromatin targeting and HAT regulation. Published online in <em>Nature Structural &#038; Molecular Biology<\/em> on 11 August 2013. DOI: 10.1038\/nsmb.2642.<\/p>\n","source_link_url":"http:\/\/dx.doi.org\/10.1038\/nsmb.2642"}],"related_links":false,"in_this_article":false,"color":"#007B53","youtube_url":"","mp4_url":"","video_caption":"","translations":false,"press_contact":"EMBL Generic"},"embl_taxonomy_terms":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v26.2 - https:\/\/yoast.com\/wordpress\/plugins\/seo\/ -->\n<title>From fireman to arsonist | EMBL<\/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.embl.org\/news\/science\/from-fireman-to-arsonist\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"From fireman to arsonist | EMBL\" \/>\n<meta property=\"og:description\" content=\"Like a fireman who becomes an arsonist, a protein that prevents cells becoming cancerous can also cause tumours, scientists at the European Molecular Biology Laboratory (EMBL) in Grenoble, France, have discovered. The finding, published today in&nbsp;Nature Structural and Molecular Biology, stems&hellip;\" \/>\n<meta property=\"og:url\" content=\"https:\/\/www.embl.org\/news\/science\/from-fireman-to-arsonist\/\" \/>\n<meta property=\"og:site_name\" content=\"EMBL\" \/>\n<meta property=\"article:publisher\" content=\"https:\/\/www.facebook.com\/embl.org\/\" \/>\n<meta property=\"article:published_time\" content=\"2013-08-11T10:49:00+00:00\" \/>\n<meta property=\"article:modified_time\" content=\"2024-03-25T23:29:29+00:00\" \/>\n<meta property=\"og:image\" content=\"https:\/\/www.embl.org\/news\/wp-content\/uploads\/2020\/05\/130811_Grenoble.jpeg\" \/>\n\t<meta property=\"og:image:width\" content=\"800\" \/>\n\t<meta property=\"og:image:height\" content=\"654\" \/>\n\t<meta property=\"og:image:type\" content=\"image\/jpeg\" \/>\n<meta name=\"author\" content=\"Guest author(s)\" \/>\n<meta name=\"twitter:card\" content=\"summary_large_image\" \/>\n<meta name=\"twitter:creator\" content=\"@embl\" \/>\n<meta name=\"twitter:site\" content=\"@embl\" \/>\n<meta name=\"twitter:label1\" content=\"Written by\" \/>\n\t<meta name=\"twitter:data1\" content=\"Guest author(s)\" \/>\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\":\"NewsArticle\",\"@id\":\"https:\/\/www.embl.org\/news\/science\/from-fireman-to-arsonist\/#article\",\"isPartOf\":{\"@id\":\"https:\/\/www.embl.org\/news\/science\/from-fireman-to-arsonist\/\"},\"author\":{\"name\":\"Guest author(s)\",\"@id\":\"https:\/\/www.embl.org\/news\/#\/schema\/person\/b4d9366b2ebe691c4015c64c3619205b\"},\"headline\":\"From fireman to arsonist\",\"datePublished\":\"2013-08-11T10:49:00+00:00\",\"dateModified\":\"2024-03-25T23:29:29+00:00\",\"mainEntityOfPage\":{\"@id\":\"https:\/\/www.embl.org\/news\/science\/from-fireman-to-arsonist\/\"},\"wordCount\":389,\"publisher\":{\"@id\":\"https:\/\/www.embl.org\/news\/#organization\"},\"image\":{\"@id\":\"https:\/\/www.embl.org\/news\/science\/from-fireman-to-arsonist\/#primaryimage\"},\"thumbnailUrl\":\"https:\/\/www.embl.org\/news\/wp-content\/uploads\/2020\/05\/130811_Grenoble.jpeg\",\"keywords\":[\"cancer\",\"drug\",\"protein\",\"tumour\"],\"articleSection\":[\"Science\",\"Science &amp; Technology\"],\"inLanguage\":\"en-US\"},{\"@type\":\"WebPage\",\"@id\":\"https:\/\/www.embl.org\/news\/science\/from-fireman-to-arsonist\/\",\"url\":\"https:\/\/www.embl.org\/news\/science\/from-fireman-to-arsonist\/\",\"name\":\"From fireman to arsonist | EMBL\",\"isPartOf\":{\"@id\":\"https:\/\/www.embl.org\/news\/#website\"},\"primaryImageOfPage\":{\"@id\":\"https:\/\/www.embl.org\/news\/science\/from-fireman-to-arsonist\/#primaryimage\"},\"image\":{\"@id\":\"https:\/\/www.embl.org\/news\/science\/from-fireman-to-arsonist\/#primaryimage\"},\"thumbnailUrl\":\"https:\/\/www.embl.org\/news\/wp-content\/uploads\/2020\/05\/130811_Grenoble.jpeg\",\"datePublished\":\"2013-08-11T10:49:00+00:00\",\"dateModified\":\"2024-03-25T23:29:29+00:00\",\"inLanguage\":\"en-US\",\"potentialAction\":[{\"@type\":\"ReadAction\",\"target\":[\"https:\/\/www.embl.org\/news\/science\/from-fireman-to-arsonist\/\"]}]},{\"@type\":\"ImageObject\",\"inLanguage\":\"en-US\",\"@id\":\"https:\/\/www.embl.org\/news\/science\/from-fireman-to-arsonist\/#primaryimage\",\"url\":\"https:\/\/www.embl.org\/news\/wp-content\/uploads\/2020\/05\/130811_Grenoble.jpeg\",\"contentUrl\":\"https:\/\/www.embl.org\/news\/wp-content\/uploads\/2020\/05\/130811_Grenoble.jpeg\",\"width\":800,\"height\":654,\"caption\":\"The 3D structure of p300 revealed a \u2018lid\u2019 (green) that controls whether or not the protein can slot the appropriate groove (arrow) onto genetic material to turn genes on or off. 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