{"id":1166,"date":"2020-01-22T16:42:58","date_gmt":"2020-01-22T16:42:58","guid":{"rendered":"https:\/\/lsom.uthscsa.edu\/molecular-medicine\/?p=1166"},"modified":"2020-01-23T19:04:21","modified_gmt":"2020-01-23T19:04:21","slug":"cenp-a-ubiquitylation-is-indispensable-to-cell-viability","status":"publish","type":"post","link":"https:\/\/lsom.uthscsa.edu\/molecular-medicine\/2020\/01\/22\/cenp-a-ubiquitylation-is-indispensable-to-cell-viability\/","title":{"rendered":"CENP-A Ubiquitylation Is Indispensable to Cell Viability"},"content":{"rendered":"<p>Abstract:<\/p>\n<p>CENP-A is a centromere-specific histone H3 variant that epigenetically determines centromere identity, but how CENP-A is deposited at the centromere remains obscure. We previously reported that CENP-A K124 ubiquitylation, mediated by the CUL4A-RBX1-COPS8 complex, is essential for CENP-A deposition at the centromere. However, a recent report stated that CENP-A K124R mutants show no defects in centromere localization and cell viability. In the present study, we found that EYFP tagging induces additional ubiquitylation of EYFP-CENP-A K124R, which allows the mutant protein to bind to HJURP. Using a previously developed conditional CENP-A knockout system and our CENP-A K124R knockin mutant created by the CRISPR-Cas9 system, we show that the Flag-tagged or untagged CENP-A K124R mutant is lethal. This lethality is rescued by monoubiquitin fusion, indicating that CENP-A ubiquitylation is essential for viability.<\/p>\n<p>&nbsp;<\/p>\n<p>Niikura Y, Kitagawa R, Fang L, <strong>Kitagawa K<\/strong>. CENP-A Ubiquitylation Is Indispensable to Cell Viability. <em>Dev Cell<\/em>. 2019 Sep 23;50(6):683-689.e6. doi:<br \/>\n10.1016\/j.devcel.2019.07.015. PubMed PMID: 31550462; PubMed Central PMCID:PMC6761987.<\/p>\n<p>&nbsp;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Abstract: CENP-A is a centromere-specific histone H3 variant that epigenetically determines centromere identity, but how CENP-A is deposited at the centromere remains obscure. We previously reported that CENP-A K124 ubiquitylation, mediated by the CUL4A-RBX1-COPS8 complex, is essential for CENP-A deposition at the centromere. However, a recent report stated that CENP-A K124R mutants show no defects [&hellip;]<\/p>\n","protected":false},"author":264,"featured_media":0,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[3,14],"class_list":["post-1166","post","type-post","status-publish","format-standard","hentry","category-highimpactpublication","category-news"],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v28.5 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>CENP-A Ubiquitylation Is Indispensable to Cell Viability - Department of Molecular Medicine<\/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:\/\/lsom.uthscsa.edu\/molecular-medicine\/2020\/01\/22\/cenp-a-ubiquitylation-is-indispensable-to-cell-viability\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"CENP-A Ubiquitylation Is Indispensable to Cell Viability - Department of Molecular Medicine\" \/>\n<meta property=\"og:description\" content=\"Abstract: CENP-A is a centromere-specific histone H3 variant that epigenetically determines centromere identity, but how CENP-A is deposited at the centromere remains obscure. We previously reported that CENP-A K124 ubiquitylation, mediated by the CUL4A-RBX1-COPS8 complex, is essential for CENP-A deposition at the centromere. However, a recent report stated that CENP-A K124R mutants show no defects [&hellip;]\" \/>\n<meta property=\"og:url\" content=\"https:\/\/lsom.uthscsa.edu\/molecular-medicine\/2020\/01\/22\/cenp-a-ubiquitylation-is-indispensable-to-cell-viability\/\" \/>\n<meta property=\"og:site_name\" content=\"Department of Molecular Medicine\" \/>\n<meta property=\"article:published_time\" content=\"2020-01-22T16:42:58+00:00\" \/>\n<meta property=\"article:modified_time\" content=\"2020-01-23T19:04:21+00:00\" \/>\n<meta name=\"author\" content=\"Allan Jenkins\" \/>\n<meta name=\"twitter:card\" content=\"summary_large_image\" \/>\n<meta name=\"twitter:label1\" content=\"Written by\" \/>\n\t<meta name=\"twitter:data1\" content=\"Allan Jenkins\" \/>\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:\\\/\\\/lsom.uthscsa.edu\\\/molecular-medicine\\\/2020\\\/01\\\/22\\\/cenp-a-ubiquitylation-is-indispensable-to-cell-viability\\\/#article\",\"isPartOf\":{\"@id\":\"https:\\\/\\\/lsom.uthscsa.edu\\\/molecular-medicine\\\/2020\\\/01\\\/22\\\/cenp-a-ubiquitylation-is-indispensable-to-cell-viability\\\/\"},\"author\":{\"name\":\"Allan Jenkins\",\"@id\":\"https:\\\/\\\/lsom.uthscsa.edu\\\/molecular-medicine\\\/#\\\/schema\\\/person\\\/f9ba93501ec712deeae4be817f0910a7\"},\"headline\":\"CENP-A Ubiquitylation Is Indispensable to Cell Viability\",\"datePublished\":\"2020-01-22T16:42:58+00:00\",\"dateModified\":\"2020-01-23T19:04:21+00:00\",\"mainEntityOfPage\":{\"@id\":\"https:\\\/\\\/lsom.uthscsa.edu\\\/molecular-medicine\\\/2020\\\/01\\\/22\\\/cenp-a-ubiquitylation-is-indispensable-to-cell-viability\\\/\"},\"wordCount\":175,\"articleSection\":[\"High Impact Publications\",\"News\"],\"inLanguage\":\"en-US\"},{\"@type\":\"WebPage\",\"@id\":\"https:\\\/\\\/lsom.uthscsa.edu\\\/molecular-medicine\\\/2020\\\/01\\\/22\\\/cenp-a-ubiquitylation-is-indispensable-to-cell-viability\\\/\",\"url\":\"https:\\\/\\\/lsom.uthscsa.edu\\\/molecular-medicine\\\/2020\\\/01\\\/22\\\/cenp-a-ubiquitylation-is-indispensable-to-cell-viability\\\/\",\"name\":\"CENP-A Ubiquitylation Is Indispensable to Cell Viability - Department of Molecular Medicine\",\"isPartOf\":{\"@id\":\"https:\\\/\\\/lsom.uthscsa.edu\\\/molecular-medicine\\\/#website\"},\"datePublished\":\"2020-01-22T16:42:58+00:00\",\"dateModified\":\"2020-01-23T19:04:21+00:00\",\"author\":{\"@id\":\"https:\\\/\\\/lsom.uthscsa.edu\\\/molecular-medicine\\\/#\\\/schema\\\/person\\\/f9ba93501ec712deeae4be817f0910a7\"},\"breadcrumb\":{\"@id\":\"https:\\\/\\\/lsom.uthscsa.edu\\\/molecular-medicine\\\/2020\\\/01\\\/22\\\/cenp-a-ubiquitylation-is-indispensable-to-cell-viability\\\/#breadcrumb\"},\"inLanguage\":\"en-US\",\"potentialAction\":[{\"@type\":\"ReadAction\",\"target\":[\"https:\\\/\\\/lsom.uthscsa.edu\\\/molecular-medicine\\\/2020\\\/01\\\/22\\\/cenp-a-ubiquitylation-is-indispensable-to-cell-viability\\\/\"]}]},{\"@type\":\"BreadcrumbList\",\"@id\":\"https:\\\/\\\/lsom.uthscsa.edu\\\/molecular-medicine\\\/2020\\\/01\\\/22\\\/cenp-a-ubiquitylation-is-indispensable-to-cell-viability\\\/#breadcrumb\",\"itemListElement\":[{\"@type\":\"ListItem\",\"position\":1,\"name\":\"Home\",\"item\":\"https:\\\/\\\/lsom.uthscsa.edu\\\/molecular-medicine\\\/\"},{\"@type\":\"ListItem\",\"position\":2,\"name\":\"News\",\"item\":\"https:\\\/\\\/lsom.uthscsa.edu\\\/molecular-medicine\\\/category\\\/news\\\/\"},{\"@type\":\"ListItem\",\"position\":3,\"name\":\"CENP-A Ubiquitylation Is Indispensable to Cell Viability\"}]},{\"@type\":\"WebSite\",\"@id\":\"https:\\\/\\\/lsom.uthscsa.edu\\\/molecular-medicine\\\/#website\",\"url\":\"https:\\\/\\\/lsom.uthscsa.edu\\\/molecular-medicine\\\/\",\"name\":\"Department of Molecular Medicine\",\"description\":\"Department of Molecular Medicine\",\"potentialAction\":[{\"@type\":\"SearchAction\",\"target\":{\"@type\":\"EntryPoint\",\"urlTemplate\":\"https:\\\/\\\/lsom.uthscsa.edu\\\/molecular-medicine\\\/?s={search_term_string}\"},\"query-input\":{\"@type\":\"PropertyValueSpecification\",\"valueRequired\":true,\"valueName\":\"search_term_string\"}}],\"inLanguage\":\"en-US\"},{\"@type\":\"Person\",\"@id\":\"https:\\\/\\\/lsom.uthscsa.edu\\\/molecular-medicine\\\/#\\\/schema\\\/person\\\/f9ba93501ec712deeae4be817f0910a7\",\"name\":\"Allan Jenkins\",\"image\":{\"@type\":\"ImageObject\",\"inLanguage\":\"en-US\",\"@id\":\"https:\\\/\\\/secure.gravatar.com\\\/avatar\\\/c7b37b4cc45d6f6a6b6862b1ab3ead86ed46ac67359c67d9613da381b7a18125?s=96&d=mm&r=g\",\"url\":\"https:\\\/\\\/secure.gravatar.com\\\/avatar\\\/c7b37b4cc45d6f6a6b6862b1ab3ead86ed46ac67359c67d9613da381b7a18125?s=96&d=mm&r=g\",\"contentUrl\":\"https:\\\/\\\/secure.gravatar.com\\\/avatar\\\/c7b37b4cc45d6f6a6b6862b1ab3ead86ed46ac67359c67d9613da381b7a18125?s=96&d=mm&r=g\",\"caption\":\"Allan Jenkins\"},\"url\":\"https:\\\/\\\/lsom.uthscsa.edu\\\/molecular-medicine\\\/author\\\/jenkinsallan\\\/\"}]}<\/script>\n<!-- \/ Yoast SEO plugin. -->","yoast_head_json":{"title":"CENP-A Ubiquitylation Is Indispensable to Cell Viability - Department of Molecular Medicine","robots":{"index":"index","follow":"follow","max-snippet":"max-snippet:-1","max-image-preview":"max-image-preview:large","max-video-preview":"max-video-preview:-1"},"canonical":"https:\/\/lsom.uthscsa.edu\/molecular-medicine\/2020\/01\/22\/cenp-a-ubiquitylation-is-indispensable-to-cell-viability\/","og_locale":"en_US","og_type":"article","og_title":"CENP-A Ubiquitylation Is Indispensable to Cell Viability - Department of Molecular Medicine","og_description":"Abstract: CENP-A is a centromere-specific histone H3 variant that epigenetically determines centromere identity, but how CENP-A is deposited at the centromere remains obscure. We previously reported that CENP-A K124 ubiquitylation, mediated by the CUL4A-RBX1-COPS8 complex, is essential for CENP-A deposition at the centromere. However, a recent report stated that CENP-A K124R mutants show no defects [&hellip;]","og_url":"https:\/\/lsom.uthscsa.edu\/molecular-medicine\/2020\/01\/22\/cenp-a-ubiquitylation-is-indispensable-to-cell-viability\/","og_site_name":"Department of Molecular Medicine","article_published_time":"2020-01-22T16:42:58+00:00","article_modified_time":"2020-01-23T19:04:21+00:00","author":"Allan Jenkins","twitter_card":"summary_large_image","twitter_misc":{"Written by":"Allan Jenkins","Est. reading time":"1 minute"},"schema":{"@context":"https:\/\/schema.org","@graph":[{"@type":"Article","@id":"https:\/\/lsom.uthscsa.edu\/molecular-medicine\/2020\/01\/22\/cenp-a-ubiquitylation-is-indispensable-to-cell-viability\/#article","isPartOf":{"@id":"https:\/\/lsom.uthscsa.edu\/molecular-medicine\/2020\/01\/22\/cenp-a-ubiquitylation-is-indispensable-to-cell-viability\/"},"author":{"name":"Allan Jenkins","@id":"https:\/\/lsom.uthscsa.edu\/molecular-medicine\/#\/schema\/person\/f9ba93501ec712deeae4be817f0910a7"},"headline":"CENP-A Ubiquitylation Is Indispensable to Cell Viability","datePublished":"2020-01-22T16:42:58+00:00","dateModified":"2020-01-23T19:04:21+00:00","mainEntityOfPage":{"@id":"https:\/\/lsom.uthscsa.edu\/molecular-medicine\/2020\/01\/22\/cenp-a-ubiquitylation-is-indispensable-to-cell-viability\/"},"wordCount":175,"articleSection":["High Impact Publications","News"],"inLanguage":"en-US"},{"@type":"WebPage","@id":"https:\/\/lsom.uthscsa.edu\/molecular-medicine\/2020\/01\/22\/cenp-a-ubiquitylation-is-indispensable-to-cell-viability\/","url":"https:\/\/lsom.uthscsa.edu\/molecular-medicine\/2020\/01\/22\/cenp-a-ubiquitylation-is-indispensable-to-cell-viability\/","name":"CENP-A Ubiquitylation Is Indispensable to Cell Viability - Department of Molecular Medicine","isPartOf":{"@id":"https:\/\/lsom.uthscsa.edu\/molecular-medicine\/#website"},"datePublished":"2020-01-22T16:42:58+00:00","dateModified":"2020-01-23T19:04:21+00:00","author":{"@id":"https:\/\/lsom.uthscsa.edu\/molecular-medicine\/#\/schema\/person\/f9ba93501ec712deeae4be817f0910a7"},"breadcrumb":{"@id":"https:\/\/lsom.uthscsa.edu\/molecular-medicine\/2020\/01\/22\/cenp-a-ubiquitylation-is-indispensable-to-cell-viability\/#breadcrumb"},"inLanguage":"en-US","potentialAction":[{"@type":"ReadAction","target":["https:\/\/lsom.uthscsa.edu\/molecular-medicine\/2020\/01\/22\/cenp-a-ubiquitylation-is-indispensable-to-cell-viability\/"]}]},{"@type":"BreadcrumbList","@id":"https:\/\/lsom.uthscsa.edu\/molecular-medicine\/2020\/01\/22\/cenp-a-ubiquitylation-is-indispensable-to-cell-viability\/#breadcrumb","itemListElement":[{"@type":"ListItem","position":1,"name":"Home","item":"https:\/\/lsom.uthscsa.edu\/molecular-medicine\/"},{"@type":"ListItem","position":2,"name":"News","item":"https:\/\/lsom.uthscsa.edu\/molecular-medicine\/category\/news\/"},{"@type":"ListItem","position":3,"name":"CENP-A Ubiquitylation Is Indispensable to Cell Viability"}]},{"@type":"WebSite","@id":"https:\/\/lsom.uthscsa.edu\/molecular-medicine\/#website","url":"https:\/\/lsom.uthscsa.edu\/molecular-medicine\/","name":"Department of Molecular Medicine","description":"Department of Molecular Medicine","potentialAction":[{"@type":"SearchAction","target":{"@type":"EntryPoint","urlTemplate":"https:\/\/lsom.uthscsa.edu\/molecular-medicine\/?s={search_term_string}"},"query-input":{"@type":"PropertyValueSpecification","valueRequired":true,"valueName":"search_term_string"}}],"inLanguage":"en-US"},{"@type":"Person","@id":"https:\/\/lsom.uthscsa.edu\/molecular-medicine\/#\/schema\/person\/f9ba93501ec712deeae4be817f0910a7","name":"Allan Jenkins","image":{"@type":"ImageObject","inLanguage":"en-US","@id":"https:\/\/secure.gravatar.com\/avatar\/c7b37b4cc45d6f6a6b6862b1ab3ead86ed46ac67359c67d9613da381b7a18125?s=96&d=mm&r=g","url":"https:\/\/secure.gravatar.com\/avatar\/c7b37b4cc45d6f6a6b6862b1ab3ead86ed46ac67359c67d9613da381b7a18125?s=96&d=mm&r=g","contentUrl":"https:\/\/secure.gravatar.com\/avatar\/c7b37b4cc45d6f6a6b6862b1ab3ead86ed46ac67359c67d9613da381b7a18125?s=96&d=mm&r=g","caption":"Allan Jenkins"},"url":"https:\/\/lsom.uthscsa.edu\/molecular-medicine\/author\/jenkinsallan\/"}]}},"_links":{"self":[{"href":"https:\/\/lsom.uthscsa.edu\/molecular-medicine\/wp-json\/wp\/v2\/posts\/1166","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/lsom.uthscsa.edu\/molecular-medicine\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/lsom.uthscsa.edu\/molecular-medicine\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/lsom.uthscsa.edu\/molecular-medicine\/wp-json\/wp\/v2\/users\/264"}],"replies":[{"embeddable":true,"href":"https:\/\/lsom.uthscsa.edu\/molecular-medicine\/wp-json\/wp\/v2\/comments?post=1166"}],"version-history":[{"count":0,"href":"https:\/\/lsom.uthscsa.edu\/molecular-medicine\/wp-json\/wp\/v2\/posts\/1166\/revisions"}],"wp:attachment":[{"href":"https:\/\/lsom.uthscsa.edu\/molecular-medicine\/wp-json\/wp\/v2\/media?parent=1166"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/lsom.uthscsa.edu\/molecular-medicine\/wp-json\/wp\/v2\/categories?post=1166"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}