{"id":7921,"date":"2016-05-25T00:23:35","date_gmt":"2016-05-25T00:23:35","guid":{"rendered":"http:\/\/www.kurzweilai.net\/?p=281009"},"modified":"2016-05-27T07:30:53","modified_gmt":"2016-05-27T07:30:53","slug":"triggering-the-protein-that-programs-cancer-cells-to-kill-themselves","status":"publish","type":"post","link":"https:\/\/hoo.central12.com\/fugic\/2016\/05\/25\/triggering-the-protein-that-programs-cancer-cells-to-kill-themselves\/","title":{"rendered":"Triggering the protein that programs cancer cells to kill themselves"},"content":{"rendered":"<p style=\"text-align: center;\"><iframe frameborder=\"0\" height=\"315\" src=\"https:\/\/www.youtube.com\/embed\/DR80Huxp4y8\" width=\"560\"><\/iframe><br \/>\n<em>WEHI | Apoptosis<\/em><\/p>\n<p>Researchers at the <a href=\"http:\/\/www.wehi.edu.au\/\" >Walter and Eliza Hall Institute<\/a> in Australia have discovered a new way to trigger cell death that could lead to drugs to treat cancer and autoimmune disease.<\/p>\n<p>Programmed cell death (a.k.a. apoptosis) is a natural process that removes unwanted cells from the body. Failure of apoptosis can allow cancer cells to grow unchecked or immune cells to inappropriately attack the body.<\/p>\n<p>The protein known as Bak is central to apoptosis. In healthy cells, Bak sits in an inert state but when a cell receives a signal to die, Bak transforms into a killer protein that destroys the cell.<\/p>\n<p><strong>Triggering the cancer-apoptosis trigger<\/strong><\/p>\n<p>Institute researchers Sweta Iyer, PhD, Ruth Kluck, PhD, and colleagues unexpectedly discovered that an antibody they had produced to study Bak actually bound to the Bak protein and triggered its activation. They hope to use this discovery to develop drugs that promote cell death.<\/p>\n<p>The researchers used information about Bak\u2019s three-dimensional structure to find out precisely how the antibody activated Bak. \u201cIt is well known that Bak can be activated by a class of proteins called \u2018BH3-only proteins\u2019 that bind to a groove on Bak. We were surprised to find that despite our antibody binding to a completely different site on Bak, it could still trigger activation,\u201d Kluck said.\u00a0 \u201cThe advantage of our antibody is that it can\u2019t be \u2018mopped up\u2019 and neutralized by pro-survival proteins in the cell, potentially reducing the chance of drug resistance occurring.\u201d<\/p>\n<p>Drugs that target this new activation site could be useful in combination with other therapies that promote cell death by mimicking the BH3-only proteins. The researchers are now working with collaborators to develop their antibody into a drug that can access Bak inside cells.<\/p>\n<p>Their findings have just been published in the open-access journal\u00a0<em><a title=\"Link to paper\" href=\"http:\/\/www.nature.com\/ncomms\/2016\/160524\/ncomms11734\/full\/ncomms11734.html\" >Nature Communications<\/a>.<\/em> The research was supported by the National Health and Medical Research Council, the Australian Research Council, the Victorian State Government Operational Infrastructure Support Scheme, and the Victorian Life Science Computation Initiative. <em><\/em><\/p>\n<hr \/>\n<p><strong>Abstract of <em>Identification of an activation site in Bak and mitochondrial Bax triggered by antibodies<\/em><\/strong><\/p>\n<p>During apoptosis, Bak and Bax are activated by BH3-only proteins binding to the\u00a0\u03b12\u2013\u03b15 hydrophobic groove; Bax is also activated via a rear pocket. Here we report that antibodies can directly activate Bak and mitochondrial Bax by binding to the\u00a0\u03b11\u2013\u03b12 loop. A monoclonal antibody (clone 7D10) binds close to\u00a0\u03b11 in non-activated Bak to induce conformational change, oligomerization, and cytochrome\u00a0<em>c<\/em>\u00a0release. Anti-FLAG antibodies also activate Bak containing a FLAG epitope close to\u00a0\u03b11. An antibody (clone 3C10) to the Bax\u00a0\u03b11\u2013\u03b12 loop activates mitochondrial Bax, but blocks translocation of cytosolic Bax. Tethers within Bak show that 7D10 binding directly extricates\u00a0\u03b11; a structural model of the 7D10 Fab bound to Bak reveals the formation of a cavity under\u00a0\u03b11. Our identification of the\u00a0\u03b11\u2013\u03b12 loop as an activation site in Bak paves the way to develop intrabodies or small molecules that directly and selectively regulate these proteins.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>WEHI | Apoptosis Researchers at the Walter and Eliza Hall Institute in Australia have discovered a new way to trigger cell death that could lead to drugs to treat cancer and autoimmune disease. Programmed cell death (a.k.a. apoptosis) is a natural process that removes unwanted cells from the body. Failure of apoptosis can allow cancer [&#8230;]<\/p>\n","protected":false},"author":13,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[42,43],"tags":[],"class_list":["post-7921","post","type-post","status-publish","format-standard","hentry","category-biotech","category-news"],"_links":{"self":[{"href":"https:\/\/hoo.central12.com\/fugic\/wp-json\/wp\/v2\/posts\/7921"}],"collection":[{"href":"https:\/\/hoo.central12.com\/fugic\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/hoo.central12.com\/fugic\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/hoo.central12.com\/fugic\/wp-json\/wp\/v2\/users\/13"}],"replies":[{"embeddable":true,"href":"https:\/\/hoo.central12.com\/fugic\/wp-json\/wp\/v2\/comments?post=7921"}],"version-history":[{"count":2,"href":"https:\/\/hoo.central12.com\/fugic\/wp-json\/wp\/v2\/posts\/7921\/revisions"}],"predecessor-version":[{"id":7926,"href":"https:\/\/hoo.central12.com\/fugic\/wp-json\/wp\/v2\/posts\/7921\/revisions\/7926"}],"wp:attachment":[{"href":"https:\/\/hoo.central12.com\/fugic\/wp-json\/wp\/v2\/media?parent=7921"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/hoo.central12.com\/fugic\/wp-json\/wp\/v2\/categories?post=7921"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/hoo.central12.com\/fugic\/wp-json\/wp\/v2\/tags?post=7921"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}