{"id":671,"date":"2017-03-14T11:53:36","date_gmt":"2017-03-14T02:53:36","guid":{"rendered":"http:\/\/www2.med.osaka-u.ac.jp\/wwwmed\/eng\/activities\/results\/2011year\/iwai-kazuhiro"},"modified":"2017-04-28T16:08:11","modified_gmt":"2017-04-28T07:08:11","slug":"article04","status":"publish","type":"page","link":"https:\/\/www.med.osaka-u.ac.jp\/eng\/activities\/results\/2011year\/article04","title":{"rendered":"IWAI Kazuhiro \u226aBiophysics and Biochemistry\u226b <span>\u201cSHARPIN is a component of the NF-kB activating linear ubiquitin chain assembly complex\u201d<\/span>"},"content":{"rendered":"<ul class=\"linkBar clearfix\">\n<li> <a href=\"http:\/\/www.med.osaka-u.ac.jp\/activities\/results\/2011year\/article04\">Text in Japanese<\/a><\/li>\n<\/ul>\n<p><!-- \n\n<h1> \u5ca9\u4e95&#12288;\u4e00\u5b8f\u226a\u533b\u5316\u5b66\u226b<\/h1>\n\n --><\/p>\n<p class=\"figure\"><a href=\"http:\/\/www.med.osaka-u.ac.jp\/eng\/wp-content\/uploads\/\/activities\/results\/2011\/iwai20110331_1.jpeg\" target=\"_blank\" class=\"zoom\"><img loading=\"lazy\" decoding=\"async\" src=\"http:\/\/www.med.osaka-u.ac.jp\/eng\/wp-content\/uploads\/\/activities\/results\/2011\/iwai20110331_1.jpeg\" alt=\"\" height=\"133\" width=\"200\" \/><\/a><\/p>\n<p>  <a href=\"http:\/\/www.med.osaka-u.ac.jp\/eng\/wp-content\/uploads\/\/activities\/results\/2011\/iwai20110331_2.jpeg\" target=\"_blank\" class=\"zoom\"><img loading=\"lazy\" decoding=\"async\" src=\"http:\/\/www.med.osaka-u.ac.jp\/eng\/wp-content\/uploads\/\/activities\/results\/2011\/iwai20110331_2.jpeg\" alt=\"\" height=\"133\" width=\"200\" \/><br \/>\n    <span class=\"click\">Click to enlarge<\/span> <\/a><\/p>\n<p>2011-3-31<br \/>\n  <span class=\"lineFrame\">Publish<\/span>Nature 471:633-636(2011)<\/p>\n<p><!-- \n\n<h3>\u6162\u6027\u76ae\u819a\u708e\u30fb\u514d\u75ab\u7570\u5e38\u306b\u95a2\u308f\u308b\u30b7\u30b0\u30ca\u30eb\u4f1d\u9054\u6a5f\u69cb\u306e\u89e3\u660e<\/h3>\n\n\n\n\n<p>NF-kB\u306f\u7a2e\u3005\u306e\u523a\u6fc0\u306b\u3088\u3063\u3066\u6d3b\u6027\u5316\u3055\u308c\u3066\u514d\u75ab\u5fdc\u7b54\u3001\u708e\u75c7\u3001\u6297\u30a2\u30dd\u30c8\u30fc\u30b7\u30b9\u4f5c\u7528\u306a\u3069\u306e\u591a\u5f69\u306a\u4f5c\u7528\u3092\u767a\u63ee\u3059\u308b\u8ee2\u5199\u56e0\u5b50\u3067\u3042\u308a\u3001\u305d\u306e\u6d3b\u6027\u8abf\u7bc0\u7570\u5e38\u304c\u76ae\u819a\u708e\u3001\u30ac\u30f3\u3092\u542b\u3081\u5e7e\u591a\u306e\u75be\u60a3\u306b\u95a2\u4e0e\u3057\u3066\u3044\u308b\u3053\u3068\u304c\u77e5\u3089\u308c\u3066\u3044\u307e\u3059\u3002\u672c\u7814\u7a76\u30c1\u30fc\u30e0\u306f\u523a\u6fc0\u306b\u5fdc\u7b54\u3057\u3066NF-kB\u306e\u6d3b\u6027\u5316\u3092\u5c0e\u304f\u65b0\u305f\u306a\u523a\u6fc0\u4f1d\u9054\u7cfb\u3068\u3057\u3066\u3001\u76f4\u9396\u72b6\u30dd\u30ea\u30e6\u30d3\u30ad\u30c1\u30f3\u9396\u3068\u547c\u3070\u308c\u308b\u5f93\u6765\u5168\u304f\u77e5\u3089\u308c\u3066\u3044\u306a\u304b\u3063\u305f\u30bf\u30f3\u30d1\u30af\u8cea\u4fee\u98fe\u7cfb\u304c\u95a2\u4e0e\u3059\u308b\u3053\u3068\u3092\u4e00\u6628\u5e74Nature Cell Biology\u8a8c\u306b\u767a\u8868\u3057\u3066\u304a\u308a\u307e\u3057\u305f\u3002<br \/>\n  \u4eca\u56de\u3001\u76f4\u9396\u72b6\u30dd\u30ea\u30e6\u30d3\u30ad\u30c1\u30f3\u9396\u3092\u9078\u629e\u7684\u306b\u751f\u6210\u3059\u308bLUBAC\u30e6\u30d3\u30ad\u30c1\u30f3\u30ea\u30ac\u30fc\u30bc\u8907\u5408\u4f53\u306e\u65b0\u898f\u69cb\u6210\u6210\u5206\u3068\u3057\u3066SHARPIN\u3092\u540c\u5b9a\u3057\u307e\u3057\u305f\u3002\u305d\u306e\u69cb\u6210\u6210\u5206\u304c\u6162\u6027\u76ae\u819a\u708e\u3001\u7a2e\u3005\u306e\u514d\u75ab\u7570\u5e38\u3001\u95a2\u7bc0\u708e\u306a\u3069\u306e\u591a\u5f69\u306a\u75c7\u72b6\u3092\u5448\u3059\u308b\u81ea\u7136\u5909\u7570\u30de\u30a6\u30b9\u306e\u8cac\u4efb\u907a\u4f1d\u5b50\u3067\u3042\u308b\u3053\u3068\u3092\u793a\u3055\u308c\u3066\u3044\u307e\u3057\u305f\u304c\u3001\u540c\u30de\u30a6\u30b9\u304c\u591a\u5f69\u306a\u75c7\u72b6\u3092\u793a\u3059\u7406\u7531\u306f\u4e0d\u660e\u3067\u3057\u305f\u3002\u672c\u7814\u7a76\u30c1\u30fc\u30e0\u306fSHARPIN\u304c\u6b20\u640d\u3059\u308b\u3053\u3068\u3067\u523a\u6fc0\u4f9d\u5b58\u7684\u306aNF-kB\u306e\u6d3b\u6027\u5316\u304c\u6e1b\u5f31\u3055\u308c\u3066\u3044\u308b\u305f\u3081\u306b\u4e0a\u8a18\u306e\u591a\u5f69\u306a\u75c7\u72b6\u3092\u5448\u3057\u3066\u3044\u308b\u3053\u3068\u3092\u793a\u3057\u307e\u3057\u305f\u3002<br \/>\n  \u4eca\u56de\u306e\u5831\u544a\u306e\u7d50\u679c\u306f\u3001\u76f4\u9396\u72b6\u30dd\u30ea\u30e6\u30d3\u30ad\u30c1\u30f3\u9396\u306e\u751f\u6210\u3092\u5236\u5fa1\u3059\u308b\u3053\u3068\u3067\u3001\u6162\u6027\u76ae\u819a\u708e\u3084\u514d\u75ab\u7570\u5e38\u304c\u95a2\u4e0e\u3059\u308b\u75be\u60a3\u306b\u5bfe\u3059\u308b\u6cbb\u7642\u6cd5\u304c\u958b\u767a\u3067\u304d\u308b\u53ef\u80fd\u6027\u3092\u5f37\u304f\u793a\u5506\u3057\u3066\u3044\u308b\u3068\u8003\u3048\u3089\u308c\u307e\u3059\u3002<\/p>\n\n --><\/p>\n<p> Cpdm (chronic proliferative dermatitis) mice develop chronic dermatitis and an immunodeficiency with increased serum IgM, symptoms that resemble those of patients with X-linked hyper-IgM syndrome and hypohydrotic ectodermal dysplasia (XHM-ED), which is caused by mutations in NEMO (NF-\u03baB essential modulator). Spontaneous null mutations in the Sharpin (SHANK-associated RH domain interacting protein in postsynaptic density) gene are responsible for the cpdm phenotype in mice. SHARPIN shows significant similarity to HOIL-1L, a component of linear ubiquitin chain assembly complex (LUBAC), which induces NF-\u03baB activation through conjugation of linear polyubiquitin chains to NEMO. Here, we identify SHARPIN as an additional component of LUBAC. SHARPIN-containing complexes can linearly ubiquitinate NEMO and activated NF-\u03baB. Thus, we re-define LUBAC as a complex containing SHARPIN, HOIL-1L, and HOIP. Deletion of SHARPIN drastically reduced the amount of LUBAC, which resulted in attenuated TNF-\u03b1- and CD40-mediated activation of NF-\u03baB in mouse embryonic fibroblasts or B cells from cpdm mice. Considering the pleomorphic phenotype of cpdm mice, these results confirm the predicted role of LUBAC-mediated linear polyubiquitination in NF-\u03baB activation induced by various stimuli, and strongly suggest the involvement of LUBAC-induced NF-\u03baB activation in various disorders.<\/p>\n<p class=\"mt25\"><span class=\"lineFrame\">URL<\/span><a href=\"http:\/\/www.cellbio.med.osaka-u.ac.jp\/\">http:\/\/www.cellbio.med.osaka-u.ac.jp\/<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"<p>Text in Japanese Click to enlarge 2011-3-31 PublishNature 471:633-636(2011) Cpdm (chronic proliferative dermat [&hellip;]<\/p>\n","protected":false},"author":1,"featured_media":1794,"parent":460,"menu_order":173,"comment_status":"closed","ping_status":"closed","template":"","meta":{"footnotes":""},"_links":{"self":[{"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/pages\/671"}],"collection":[{"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/comments?post=671"}],"version-history":[{"count":7,"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/pages\/671\/revisions"}],"predecessor-version":[{"id":2389,"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/pages\/671\/revisions\/2389"}],"up":[{"embeddable":true,"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/pages\/460"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/media\/1794"}],"wp:attachment":[{"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/media?parent=671"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}