{"id":5333,"date":"2020-05-12T14:09:23","date_gmt":"2020-05-12T14:09:23","guid":{"rendered":"http:\/\/www.sci.muni.cz\/ofiz\/?p=5333"},"modified":"2020-05-12T14:09:25","modified_gmt":"2020-05-12T14:09:25","slug":"activity-of-smurf2-ubiquitin-ligase-is-regulated-by-the-wnt-pathway-protein-dishevelled-2","status":"publish","type":"post","link":"https:\/\/ueb1.sci.muni.cz\/ofiz\/en\/activity-of-smurf2-ubiquitin-ligase-is-regulated-by-the-wnt-pathway-protein-dishevelled-2\/","title":{"rendered":"Activity of Smurf2 Ubiquitin Ligase Is Regulated by the Wnt Pathway Protein Dishevelled"},"content":{"rendered":"\n<h5 style=\"text-align: right;\"><em>Cells<\/em> <b>2020<\/b>, 9(5), 1147.<\/h5>\n\n\n\n<figure class=\"wp-block-image\"><img loading=\"lazy\" decoding=\"async\" width=\"1024\" height=\"932\" src=\"https:\/\/www.sci.muni.cz\/ofiz\/wp-content\/uploads\/2020\/05\/Smurf_Figure2_fin-1024x932.gif\" alt=\"\" class=\"wp-image-5318\" srcset=\"https:\/\/ueb1.sci.muni.cz\/ofiz\/wp-content\/uploads\/2020\/05\/Smurf_Figure2_fin-1024x932.gif 1024w, https:\/\/ueb1.sci.muni.cz\/ofiz\/wp-content\/uploads\/2020\/05\/Smurf_Figure2_fin-300x273.gif 300w, https:\/\/ueb1.sci.muni.cz\/ofiz\/wp-content\/uploads\/2020\/05\/Smurf_Figure2_fin-768x699.gif 768w, https:\/\/ueb1.sci.muni.cz\/ofiz\/wp-content\/uploads\/2020\/05\/Smurf_Figure2_fin-848x772.gif 848w, https:\/\/ueb1.sci.muni.cz\/ofiz\/wp-content\/uploads\/2020\/05\/Smurf_Figure2_fin-560x510.gif 560w\" sizes=\"auto, (max-width: 1024px) 100vw, 1024px\" \/><\/figure>\n\n\n\n<p><strong>ABSTRACT<\/strong><\/p>\n<p style=\"text-align: justify;\">Wnt and BMP signaling pathways are two key molecular machineries regulating development and homeostasis. The efficient coordination of Wnt and BMP is essential in many developmental processes such as establishment of antero-posterior and dorso-ventral body axis, regulation of convergent extension, or development of various organ systems. SMAD ubiquitination regulatory factor (Smurf) family of E3 ubiquitin ligases are important and evolutionary conserved regulators of TGF-\u03b2\/BMP signaling pathways. Smurf2 has been previously shown to regulate Wnt\/planar cell polarity (PCP) signaling pathway by ubiquitinating Prickle1, one of the key components of PCP. We explored the role of Smurf2 in Wnt pathways in further detail and identified that Smurf2 is also a ubiquitin ligase of Dishevelled (DVL), the key cytoplasmic signal transducer in the Wnt pathway. Interestingly, the Smurf2 and DVL relationship expands beyond substrate-E3 ligase. We can show that DVL activates Smurf2, which allows Smurf2 to ubiquitinate its substrates from Wnt\/PCP (Prickle1) as well as TGF-\u03b2\/BMP (Smad2) pathways more efficiently. Using SMAD7 as an example of Smurf2 activator we show that DVL and SMAD7 both activates Smurf2 activity. In HEK293 cells the deficiency of DVL phenocopies absence of Smurf2 and leads to the increased phosphorylation of R-Smads. Smurf2-DVL connection provides a novel and intriguing point of crosstalk for Wnt and BMP pathways.<\/p>\n\n\n\n<h5 style=\"text-align: center;\">by <strong>Ondrej Bernatik<\/strong>, <strong>Petra Paclikova<\/strong>, <strong>Ranjani Sri Ganji <\/strong>and <strong>Vitezslav Bryja<\/strong><sup><br><\/sup><\/h5>\n\n\n\n<h5 style=\"text-align: right;\">Read the whole story here: <a class=\"css-4rbku5 css-18t94o4 css-901oao css-16my406 r-1n1174f r-1loqt21 r-1qd0xha r-ad9z0x r-bcqeeo r-qvutc0\" dir=\"ltr\" title=\"https:\/\/bit.ly\/smurfDVL\" role=\"link\" href=\"https:\/\/t.co\/vm9W3CzQ4L?amp=1\" target=\"_blank\" rel=\"noopener noreferrer\" data-focusable=\"true\">bit.ly\/smurfDVL<\/a><\/h5>\n\n\n<style>#kt-layout-id_987496-20 > .kt-row-column-wrap{align-content:start;}:where(#kt-layout-id_987496-20 > .kt-row-column-wrap) > .wp-block-kadence-column{justify-content:start;}#kt-layout-id_987496-20 > .kt-row-column-wrap{column-gap:var(--global-kb-gap-md, 2rem);row-gap:var(--global-kb-gap-md, 2rem);padding-top:var( --global-kb-row-default-top, 25px );padding-bottom:var( --global-kb-row-default-bottom, 25px );padding-top:var(--global-kb-spacing-sm, 1.5rem);padding-bottom:var(--global-kb-spacing-sm, 1.5rem);grid-template-columns:repeat(2, minmax(0, 1fr));}#kt-layout-id_987496-20 > .kt-row-layout-overlay{opacity:0.30;}@media all and (max-width: 1024px){#kt-layout-id_987496-20 > .kt-row-column-wrap{grid-template-columns:repeat(2, minmax(0, 1fr));}}@media all and (max-width: 767px){#kt-layout-id_987496-20 > .kt-row-column-wrap{grid-template-columns:minmax(0, 1fr);}}<\/style>\n<div class=\"wp-block-kadence-rowlayout alignnone\"><div id=\"kt-layout-id_987496-20\" class=\"kt-row-layout-inner  kt-layout-id_987496-20\"><div class=\"kt-row-column-wrap kt-has-2-columns kt-gutter-default kt-v-gutter-default kt-row-valign-top kt-row-layout-equal kt-tab-layout-inherit kt-m-colapse-left-to-right kt-mobile-layout-row\"><style>.kadence-column_65b749-e7 > .kt-inside-inner-col{border-top-width:0px;border-right-width:0px;border-bottom-width:0px;border-left-width:0px;}.kadence-column_65b749-e7 > .kt-inside-inner-col,.kadence-column_65b749-e7 > .kt-inside-inner-col:before{border-top-left-radius:0px;border-top-right-radius:0px;border-bottom-right-radius:0px;border-bottom-left-radius:0px;}.kadence-column_65b749-e7 > .kt-inside-inner-col{column-gap:var(--global-kb-gap-sm, 1rem);}.kadence-column_65b749-e7 > .kt-inside-inner-col{flex-direction:column;}.kadence-column_65b749-e7 > .kt-inside-inner-col > .aligncenter{width:100%;}.kadence-column_65b749-e7 > .kt-inside-inner-col:before{opacity:0.3;}.kadence-column_65b749-e7{position:relative;}@media all and (max-width: 1024px){.kadence-column_65b749-e7 > .kt-inside-inner-col{flex-direction:column;justify-content:center;}}@media all and (max-width: 767px){.kadence-column_65b749-e7 > .kt-inside-inner-col{flex-direction:column;justify-content:center;}}<\/style>\n<div class=\"wp-block-kadence-column inner-column-1 kadence-column_65b749-e7\"><div class=\"kt-inside-inner-col\">\n<figure class=\"wp-block-image\"><img loading=\"lazy\" decoding=\"async\" width=\"1024\" height=\"775\" src=\"http:\/\/www.sci.muni.cz\/ofiz\/wp-content\/uploads\/2020\/05\/Smurf_SMALL_FIN_3-1024x775.png\" alt=\"\" class=\"wp-image-5330\" srcset=\"https:\/\/ueb1.sci.muni.cz\/ofiz\/wp-content\/uploads\/2020\/05\/Smurf_SMALL_FIN_3-1024x775.png 1024w, https:\/\/ueb1.sci.muni.cz\/ofiz\/wp-content\/uploads\/2020\/05\/Smurf_SMALL_FIN_3-300x227.png 300w, https:\/\/ueb1.sci.muni.cz\/ofiz\/wp-content\/uploads\/2020\/05\/Smurf_SMALL_FIN_3-768x581.png 768w, https:\/\/ueb1.sci.muni.cz\/ofiz\/wp-content\/uploads\/2020\/05\/Smurf_SMALL_FIN_3.png 1117w\" sizes=\"auto, (max-width: 1024px) 100vw, 1024px\" \/><\/figure>\n<\/div><\/div>\n\n\n<style>.kadence-column_cb590c-97 > .kt-inside-inner-col{border-top-width:0px;border-right-width:0px;border-bottom-width:0px;border-left-width:0px;}.kadence-column_cb590c-97 > .kt-inside-inner-col,.kadence-column_cb590c-97 > .kt-inside-inner-col:before{border-top-left-radius:0px;border-top-right-radius:0px;border-bottom-right-radius:0px;border-bottom-left-radius:0px;}.kadence-column_cb590c-97 > .kt-inside-inner-col{column-gap:var(--global-kb-gap-sm, 1rem);}.kadence-column_cb590c-97 > .kt-inside-inner-col{flex-direction:column;}.kadence-column_cb590c-97 > .kt-inside-inner-col > .aligncenter{width:100%;}.kadence-column_cb590c-97 > .kt-inside-inner-col:before{opacity:0.3;}.kadence-column_cb590c-97{position:relative;}@media all and (max-width: 1024px){.kadence-column_cb590c-97 > .kt-inside-inner-col{flex-direction:column;justify-content:center;}}@media all and (max-width: 767px){.kadence-column_cb590c-97 > .kt-inside-inner-col{flex-direction:column;justify-content:center;}}<\/style>\n<div class=\"wp-block-kadence-column inner-column-2 kadence-column_cb590c-97\"><div class=\"kt-inside-inner-col\">\n<figure class=\"wp-block-image\"><img loading=\"lazy\" decoding=\"async\" width=\"1024\" height=\"773\" src=\"http:\/\/www.sci.muni.cz\/ofiz\/wp-content\/uploads\/2020\/05\/Smurf_SMALL_FIN_2-1024x773.png\" alt=\"\" class=\"wp-image-5329\" srcset=\"https:\/\/ueb1.sci.muni.cz\/ofiz\/wp-content\/uploads\/2020\/05\/Smurf_SMALL_FIN_2-1024x773.png 1024w, https:\/\/ueb1.sci.muni.cz\/ofiz\/wp-content\/uploads\/2020\/05\/Smurf_SMALL_FIN_2-300x226.png 300w, https:\/\/ueb1.sci.muni.cz\/ofiz\/wp-content\/uploads\/2020\/05\/Smurf_SMALL_FIN_2-768x579.png 768w, https:\/\/ueb1.sci.muni.cz\/ofiz\/wp-content\/uploads\/2020\/05\/Smurf_SMALL_FIN_2.png 1120w\" sizes=\"auto, (max-width: 1024px) 100vw, 1024px\" \/><\/figure>\n<\/div><\/div>\n<\/div><\/div><\/div>\n","protected":false},"excerpt":{"rendered":"<p>Cells 2020, 9(5), 1147. ABSTRACT Wnt and BMP signaling pathways are two key molecular machineries regulating development and homeostasis. The efficient coordination of Wnt and BMP is essential in many developmental processes such as establishment of antero-posterior and dorso-ventral body &hellip; <a href=\"https:\/\/ueb1.sci.muni.cz\/ofiz\/en\/activity-of-smurf2-ubiquitin-ligase-is-regulated-by-the-wnt-pathway-protein-dishevelled-2\/\">Read More<\/a><\/p>\n","protected":false},"author":5,"featured_media":5318,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"kt_blocks_editor_width":"","_exactmetrics_skip_tracking":false,"_exactmetrics_sitenote_active":false,"_exactmetrics_sitenote_note":"","_exactmetrics_sitenote_category":0,"footnotes":""},"categories":[412,256],"tags":[],"class_list":["post-5333","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-bryjalab","category-new-paper"],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v26.1.1 - https:\/\/yoast.com\/wordpress\/plugins\/seo\/ -->\n<title>Activity of Smurf2 Ubiquitin Ligase Is Regulated by the Wnt Pathway Protein Dishevelled - Department of Animal Physiology and Immunology<\/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:\/\/ueb1.sci.muni.cz\/ofiz\/en\/activity-of-smurf2-ubiquitin-ligase-is-regulated-by-the-wnt-pathway-protein-dishevelled-2\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Activity of Smurf2 Ubiquitin Ligase Is Regulated by the Wnt Pathway Protein Dishevelled - Department of Animal Physiology and Immunology\" \/>\n<meta property=\"og:description\" content=\"Cells 2020, 9(5), 1147. ABSTRACT Wnt and BMP signaling pathways are two key molecular machineries regulating development and homeostasis. The efficient coordination of Wnt and BMP is essential in many developmental processes such as establishment of antero-posterior and dorso-ventral body &hellip; Read More\" \/>\n<meta property=\"og:url\" content=\"https:\/\/ueb1.sci.muni.cz\/ofiz\/en\/activity-of-smurf2-ubiquitin-ligase-is-regulated-by-the-wnt-pathway-protein-dishevelled-2\/\" \/>\n<meta property=\"og:site_name\" content=\"Department of Animal Physiology and Immunology\" \/>\n<meta property=\"article:published_time\" content=\"2020-05-12T14:09:23+00:00\" \/>\n<meta property=\"article:modified_time\" content=\"2020-05-12T14:09:25+00:00\" \/>\n<meta property=\"og:image\" content=\"https:\/\/ueb1.sci.muni.cz\/ofiz\/wp-content\/uploads\/2020\/05\/Smurf_Figure2_fin-1024x932.gif\" \/>\n\t<meta property=\"og:image:width\" content=\"1024\" \/>\n\t<meta property=\"og:image:height\" content=\"932\" \/>\n\t<meta property=\"og:image:type\" content=\"image\/gif\" \/>\n<meta name=\"author\" content=\"Lucie Nesvadbov\u00e1\" \/>\n<meta name=\"twitter:card\" content=\"summary_large_image\" \/>\n<meta name=\"twitter:label1\" content=\"Written by\" \/>\n\t<meta name=\"twitter:data1\" content=\"Lucie Nesvadbov\u00e1\" \/>\n\t<meta name=\"twitter:label2\" content=\"Est. 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:\/\/ueb1.sci.muni.cz\/ofiz\/en\/activity-of-smurf2-ubiquitin-ligase-is-regulated-by-the-wnt-pathway-protein-dishevelled-2\/#article\",\"isPartOf\":{\"@id\":\"https:\/\/ueb1.sci.muni.cz\/ofiz\/en\/activity-of-smurf2-ubiquitin-ligase-is-regulated-by-the-wnt-pathway-protein-dishevelled-2\/\"},\"author\":{\"name\":\"Lucie Nesvadbov\u00e1\",\"@id\":\"https:\/\/ueb1.sci.muni.cz\/ofiz\/#\/schema\/person\/3119766c8e4c78f08bbbde220469aee6\"},\"headline\":\"Activity of Smurf2 Ubiquitin Ligase Is Regulated by the Wnt Pathway Protein Dishevelled\",\"datePublished\":\"2020-05-12T14:09:23+00:00\",\"dateModified\":\"2020-05-12T14:09:25+00:00\",\"mainEntityOfPage\":{\"@id\":\"https:\/\/ueb1.sci.muni.cz\/ofiz\/en\/activity-of-smurf2-ubiquitin-ligase-is-regulated-by-the-wnt-pathway-protein-dishevelled-2\/\"},\"wordCount\":248,\"publisher\":{\"@id\":\"https:\/\/ueb1.sci.muni.cz\/ofiz\/#organization\"},\"image\":{\"@id\":\"https:\/\/ueb1.sci.muni.cz\/ofiz\/en\/activity-of-smurf2-ubiquitin-ligase-is-regulated-by-the-wnt-pathway-protein-dishevelled-2\/#primaryimage\"},\"thumbnailUrl\":\"https:\/\/ueb1.sci.muni.cz\/ofiz\/wp-content\/uploads\/2020\/05\/Smurf_Figure2_fin.gif\",\"articleSection\":[\"Bryjalab\",\"New paper\"],\"inLanguage\":\"en-US\"},{\"@type\":\"WebPage\",\"@id\":\"https:\/\/ueb1.sci.muni.cz\/ofiz\/en\/activity-of-smurf2-ubiquitin-ligase-is-regulated-by-the-wnt-pathway-protein-dishevelled-2\/\",\"url\":\"https:\/\/ueb1.sci.muni.cz\/ofiz\/en\/activity-of-smurf2-ubiquitin-ligase-is-regulated-by-the-wnt-pathway-protein-dishevelled-2\/\",\"name\":\"Activity of Smurf2 Ubiquitin Ligase Is Regulated by the Wnt Pathway Protein Dishevelled - 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ABSTRACT Wnt and BMP signaling pathways are two key molecular machineries regulating development and homeostasis. 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