{"id":2565,"date":"2017-01-25T13:18:00","date_gmt":"2017-01-25T13:18:00","guid":{"rendered":"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/?p=2565"},"modified":"2024-01-09T13:25:22","modified_gmt":"2024-01-09T13:25:22","slug":"recognition-and-small-molecule-mimicry-of-degrons-by-e3-ligases","status":"publish","type":"post","link":"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/2017\/01\/25\/recognition-and-small-molecule-mimicry-of-degrons-by-e3-ligases\/","title":{"rendered":"Recognition and small-molecule mimicry of degrons by E3 ligases"},"content":{"rendered":"<p><\/p>\n\n\n<p>Our review on recognition and small-molecule mimicry of degrons by E3 ligases is now published in Current Opinion in Structural Biology.<\/p>\n\n\n\n<p>Well done Xavi!<\/p>\n\n\n\n<p><a href=\"http:\/\/dx.doi.org\/10.1016\/j.sbi.2016.12.015\">Read our review<\/a>.<\/p>\n\n\n\n<p><strong>Highlights:<\/strong><\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>E3 ligases recruit substrates for proteasomal degradation by recognition of degrons<\/li>\n\n\n\n<li>Crystal structures reveal the structural basis and mechanism of degron recognition<\/li>\n\n\n\n<li>Small-molecule degron mimetics can prevent or re-direct substrate recognition<\/li>\n\n\n\n<li>Small-molecule inducible degrons and PROTACs enable targeted protein degradation<\/li>\n<\/ul>\n\n\n\n<h2 class=\"wp-block-heading\"><strong>Abstract<\/strong><\/h2>\n\n\n\n<p>The ubiquitin\u2013proteasome system is a master regulator of protein homeostasis, by which proteins are initially targeted for poly-ubiquitination by E3 ligases and then degraded into short peptides by the proteasome. Nature evolved diverse peptidic motifs, termed degrons, to signal substrates for degradation. We discuss degrons of the N-end rule pathway and also degrons characterized by post-translational modifications, including phosphorylation and hydroxylation. In each case we detail the structural basis of E3 ligase:degron recognition and small-molecule mimicry approaches that disrupt those protein\u2013protein interactions. We present as well genetic and chemical technologies that enable targeted degradation of proteins of interest, namely small-molecule dependent inducible degrons and chemical degraders, for example, proteolysis-targeting chimeras (PROTACs).<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Our review on recognition and small-molecule mimicry of degrons by E3 ligases is now published in Current Opinion in Structural Biology. Well done Xavi! Read our review. Highlights: Abstract The ubiquitin\u2013proteasome system is a master regulator of protein homeostasis, by which proteins are initially targeted for poly-ubiquitination by E3 ligases and then degraded into short [&hellip;]<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[19,4],"tags":[],"class_list":["post-2565","post","type-post","status-publish","format-standard","hentry","category-19","category-news"],"blocksy_meta":[],"_links":{"self":[{"href":"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-json\/wp\/v2\/posts\/2565","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-json\/wp\/v2\/comments?post=2565"}],"version-history":[{"count":0,"href":"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-json\/wp\/v2\/posts\/2565\/revisions"}],"wp:attachment":[{"href":"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-json\/wp\/v2\/media?parent=2565"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-json\/wp\/v2\/categories?post=2565"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-json\/wp\/v2\/tags?post=2565"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}