{"id":1288,"date":"2015-11-23T22:27:47","date_gmt":"2015-11-23T21:27:47","guid":{"rendered":"http:\/\/blogs.lshtm.ac.uk\/alsfordlab\/?p=1288"},"modified":"2015-11-27T21:32:14","modified_gmt":"2015-11-27T20:32:14","slug":"ubiquitination-influences-suramin-efficacy","status":"publish","type":"post","link":"https:\/\/blogs.lshtm.ac.uk\/alsfordlab\/2015\/11\/23\/ubiquitination-influences-suramin-efficacy\/","title":{"rendered":"Ubiquitination influences suramin efficacy"},"content":{"rendered":"

Suramin is one of the oldest drugs still in use today – it’s been used to treat early stage human African trypanosomiasis caused by T. b. rhodesiense<\/em> since the early 1920s.\u00a0Back in 2012 we\u00a0showed that suramin uptake was dependent on receptor mediated endocytosis and relied on a complex network of proteins from ISG75 in the flagellar pocket to cathepsin-L and MFST in the lysosome (Alsford et al 2012<\/a>).<\/p>\n

We recently contributed to a study led\u00a0by Prof Mark Field’s group<\/a> at the University of Dundee, which revealed that two ubiquitin hydrolases (TbUsp7 and TbVdu1) modulate the surface expression and turnover of ISG75 (as well as several other proteins), thereby affecting parasite sensitivity to suramin.<\/p>\n

Modulation of the surface proteome through multiple ubiquitylation pathways in African trypanosomes.<\/strong>
\nPLoS Pathogens<\/em> 11: e1005236<\/a><\/p>\n

SILAC analyses revealed that both hydrolases have a high degree of\u00a0specificity. The effect of TbVdu1 depletion decreases ISG75 and ISG65 protein levels in T. brucei<\/em>, while loss of TbUsp1 impacts ISG75 and a small cohort of other endosomal proteins, including an orthologue of VAMP7b and MBAP1. These changes in ISG75 protein levels elicited by the loss of either of these regulatory proteins\u00a0impacts drug\u00a0efficacy, rendering the parasite\u00a0significantly less sensitive to suramin.<\/p>\n","protected":false},"excerpt":{"rendered":"

Suramin is one of the oldest drugs still in use today – it’s been used…<\/p>\n","protected":false},"author":116,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[12450],"tags":[],"class_list":["post-1288","post","type-post","status-publish","format-standard","hentry","category-publication","odd"],"yoast_head":"\nUbiquitination influences suramin efficacy - Alsford Lab<\/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:\/\/blogs.lshtm.ac.uk\/alsfordlab\/2015\/11\/23\/ubiquitination-influences-suramin-efficacy\/\" \/>\n<meta property=\"og:locale\" content=\"en_GB\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Ubiquitination influences suramin efficacy - Alsford Lab\" \/>\n<meta property=\"og:description\" content=\"Suramin is one of the oldest drugs still in use today – it’s been used...\" \/>\n<meta property=\"og:url\" content=\"https:\/\/blogs.lshtm.ac.uk\/alsfordlab\/2015\/11\/23\/ubiquitination-influences-suramin-efficacy\/\" \/>\n<meta property=\"og:site_name\" content=\"Alsford Lab\" \/>\n<meta property=\"article:published_time\" content=\"2015-11-23T21:27:47+00:00\" \/>\n<meta property=\"article:modified_time\" content=\"2015-11-27T20:32:14+00:00\" \/>\n<meta name=\"author\" content=\"Sam Alsford\" \/>\n<meta name=\"twitter:label1\" content=\"Written by\" \/>\n\t<meta name=\"twitter:data1\" content=\"Sam Alsford\" \/>\n\t<meta name=\"twitter:label2\" content=\"Estimated reading time\" \/>\n\t<meta name=\"twitter:data2\" content=\"1 minute\" \/>\n<script type=\"application\/ld+json\" class=\"yoast-schema-graph\">{\"@context\":\"https:\/\/schema.org\",\"@graph\":[{\"@type\":\"Article\",\"@id\":\"https:\/\/blogs.lshtm.ac.uk\/alsfordlab\/2015\/11\/23\/ubiquitination-influences-suramin-efficacy\/#article\",\"isPartOf\":{\"@id\":\"https:\/\/blogs.lshtm.ac.uk\/alsfordlab\/2015\/11\/23\/ubiquitination-influences-suramin-efficacy\/\"},\"author\":{\"name\":\"Sam Alsford\",\"@id\":\"https:\/\/blogs.lshtm.ac.uk\/alsfordlab\/#\/schema\/person\/5005c5aa631c3c4da712ea95e66f76cd\"},\"headline\":\"Ubiquitination influences suramin efficacy\",\"datePublished\":\"2015-11-23T21:27:47+00:00\",\"dateModified\":\"2015-11-27T20:32:14+00:00\",\"mainEntityOfPage\":{\"@id\":\"https:\/\/blogs.lshtm.ac.uk\/alsfordlab\/2015\/11\/23\/ubiquitination-influences-suramin-efficacy\/\"},\"wordCount\":210,\"articleSection\":[\"Publication\"],\"inLanguage\":\"en-GB\"},{\"@type\":\"WebPage\",\"@id\":\"https:\/\/blogs.lshtm.ac.uk\/alsfordlab\/2015\/11\/23\/ubiquitination-influences-suramin-efficacy\/\",\"url\":\"https:\/\/blogs.lshtm.ac.uk\/alsfordlab\/2015\/11\/23\/ubiquitination-influences-suramin-efficacy\/\",\"name\":\"Ubiquitination influences suramin efficacy - 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