{"id":660,"date":"2017-03-14T11:51:31","date_gmt":"2017-03-14T02:51:31","guid":{"rendered":"http:\/\/www2.med.osaka-u.ac.jp\/wwwmed\/eng\/activities\/results\/2009year\/iwai-kazuhiro"},"modified":"2017-04-28T15:32:05","modified_gmt":"2017-04-28T06:32:05","slug":"article09","status":"publish","type":"page","link":"https:\/\/www.med.osaka-u.ac.jp\/eng\/activities\/results\/2009year\/article09","title":{"rendered":"IWAI Kazuhiro \u226aBiophysics and Biochemistry\u226b <span>\u201cInvolvement of linear   polyubiquitylation of NEMO in NF-\u03baB activation\u201d<\/span>"},"content":{"rendered":"<ul class=\"linkBar clearfix\">\n<li> <a href=\"http:\/\/www.med.osaka-u.ac.jp\/activities\/results\/2009year\/article09\">Text in Japanese<\/a><\/li>\n<\/ul>\n<p><!-- \n\n<h1>\u5ca9\u4e95 \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\/2009\/iwai200901.jpeg\" target=\"_blank\" class=\"zoom\"><img loading=\"lazy\" decoding=\"async\" src=\"http:\/\/www.med.osaka-u.ac.jp\/eng\/wp-content\/uploads\/\/activities\/results\/2009\/iwai200901.jpeg\" alt=\"\" height=\"138\" width=\"200\" \/><br \/>\n  <span class=\"click\">Click to enlarge<\/span><\/a><\/p>\n<p>2009-1-11<br \/>\n  <span class=\"lineFrame\">Publish<\/span> Nature Cell Biology 11,123-132, 2009<\/p>\n<p><!-- \n\n<h3>\u708e\u75c7\u3001\u304c\u3093\u5316\u306b\u95a2\u308f\u308b\u65b0\u305f\u306aNF-\u03baB\u6d3b\u6027\u5316\u6a5f\u69cb\u306e\u767a\u898b<\/h3>\n\n\n\n\n<p>\u7814\u7a76\u306e\u80cc\u666f:\u30e6\u30d3\u30ad\u30c1\u30f3\u4fee\u98fe\u7cfb\u306f\u30bf\u30f3\u30d1\u30af\u8cea\u304c\u51fa\u6765\u4e0a\u304c\u3063\u305f\u5f8c\u306b\u3001\u30e6\u30d3\u30ad\u30c1\u30f3\u304c\u8907\u6570\u500b\u6570\u73e0\u72b6\u306b\u7e4b\u304c\u3063\u3066\u5f62\u6210\u3055\u308c  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\u72b6\u30dd\u30ea\u30e6\u30d3\u30ad\u30c1\u30f3\u5316\u3055\u308c\u308b\u30bf\u30f3\u30d1\u30af\u8cea\u3092\u691c\u7d22\u3057\u305f\u3002\u305d\u306e\u7d50\u679c\u3001\u7d30\u80de\u304c\u708e\u75c7\u6027\u30b5\u30a4\u30c8\u30ab\u30a4\u30f3\u306a\u3069\u3067\u523a\u6fc0\u3092\u53d7\u3051\u305f\u3042\u3068\u3001\u540c\u8907\u5408\u4f53\u306fNEMO\u3068\u547c\u3070\u308c\u308bNF-\u03baB\u306e  \u6d3b\u6027\u5316\u306b\u975e\u5e38\u306b\u91cd\u8981\u306a\u5f79\u5272\u3092\u679c\u305f\u3059\u30bf\u30f3\u30d1\u30af\u8cea\u3068\u9078\u629e\u7684\u306b\u7d50\u5408\u3057\u3066\u3001NEMO   \u306b\u76f4\u9396\u72b6\u30dd\u30ea\u30e6\u30d3\u30ad\u30c1\u30f3\u3092\u4ed8\u52a0\u3059\u308b\u3053\u3068\u3067NF-\u03baB\u306e\u6d3b\u6027\u5316\u306b\u5c0e\u304f\u3053\u3068\u3092\u660e\u3089\u304b\u306b\u3057\u305f\uff08\u56f3\uff09\u3002\u3055\u3089\u306b\u3001\u76f4\u9396\u72b6\u30dd\u30ea\u30e6\u30d3\u30ad\u30c1\u30f3\u9396\u3092\u751f\u6210\u3059\u308b\u30e6\u30d3\u30ad\u30c1\u30f3\u30ea\u30ac\u30fc  \u30bc\u8907\u5408\u4f53\u306e\u69cb\u6210\u6210\u5206\u306e\uff11\u3064\u3067\u3042\u308bHOIL-1L\u3092\u6b20\u640d\u3057\u3066\u3044\u308b\u30de\u30a6\u30b9\u7531\u6765\u306e\u809d\u7d30\u80de\u3067\u306fTNF-\u03b1\u4f9d\u5b58\u7684\u306aNF-\u03baB\u306e\u6d3b\u6027\u5316\u304c\u8457\u3057\u304f\u6e1b\u5f31\u3059\u308b\u3053\u3068\u3092\u793a\u3057  \u305f\u3002\u3053\u308c\u307e\u3067\u306b\u3082\u3001\u30dd\u30ea\u30e6\u30d3\u30ad\u30c1\u30f3\u5316\u306f\u591a\u5f69\u306a\u69d8\u5f0f\u3067NF-\u03baB\u306e\u6d3b\u6027\u5316\u306b\u95a2\u4e0e\u3059\u308b\u3053\u3068\u304c\u77e5\u3089\u308c\u3066\u306f\u3044\u305f\u304c\u3001\u305d\u306e\u3044\u305a\u308c\u3082\u304cNF-\u03baB\u9078\u629e\u7684\u3067\u306f\u306a\u3044\u306e\u306b\u5bfe  \u3057\u3001\u76f4\u9396\u72b6\u30dd\u30ea\u30e6\u30d3\u30ad\u30c1\u30f3\u9396\u306fNF-\u03baB\u3092\u7279\u7570\u7684\u306b\u6d3b\u6027\u5316\u3059\u308b\u3068\u601d\u308f\u308c\u308b\u3053\u3068\u3092\u793a\u3057\u305f\u3002<\/p>\n\n\n\n\n<p>\u4eca\u5f8c\u671f\u5f85\u3067\u304d\u308b\u6210\u679c\uff1a\u524d\u8ff0\u306e\u3088\u3046\u306b\u3001NF-\u03baB\u306f\u30ea\u30a6\u30de\u30c1\u306a\u3069\u306e\u514d\u75ab\u7570\u5e38\u3092\u4f34\u3046\u75be\u60a3\u3001\u30a2\u30ec\u30eb\u30ae\u30fc\u3001\u30ac\u30f3\u306a\u3069\u306e\u591a\u5f69\u306a\u75be\u60a3\u306b\u95a2\u308f\u3063\u3066\u3044\u308b\u3002\u3055\u3089\u306b\u3001\u76f4\u9396\u72b6\u30dd  \u30ea\u30e6\u30d3\u30ad\u30c1\u30f3\u5316\u306f\u3053\u308c\u307e\u3067\u306e\u3068\u3053\u308d\u4ed6\u306e\u523a\u6fc0\u4f1d\u9054\u7cfb\u306b\u306f\u5f71\u97ff\u3092\u53ca\u307c\u3055\u305a\u3001NF-\u03baB\u3092\u7279\u7570\u7684\u306b\u5236\u5fa1\u3057\u3066\u3044\u308b\u3002\u305d\u308c\u3086\u3048\u3001\u76f4\u9396\u72b6\u30dd\u30ea\u30e6\u30d3\u30ad\u30c1\u30f3\u5316\u306fNF-\u03baB  \u306e\u6d3b\u6027\u3092\u8abf\u7bc0\u3059\u308b\u85ac\u5264\u306e\u826f\u3044\u30bf\u30fc\u30b2\u30c3\u30c8\u306b\u306a\u308b\u3053\u3068\u304c\u671f\u5f85\u3055\u308c\u308b\u3002<\/p>\n\n --><\/p>\n<p>Nuclear factor-\u03baB (NF-\u03baB) is a   key transcription factor in inflammatory, anti-apoptotic and immune   processes. The ubiquitin pathwayis crucial in regulating the NF-\u03baB   pathway. We have found that the LUBAC ligase complex, composed of the   two RING finger proteins, HOIL-1L and HOIP, conjugates a   head-to-tail-linked linear polyubiquitin chain to substrates. Here, we   demonstrate that LUBAC activates the canonical NF-\u03baB pathway by binding   to NEMO (NF-\u03baB essential modulator, also called IKK\u03b3) and conjugates   linear polyubiquitin chains onto specific Lys residues in the CC2-LZ   domain of NEMO in a Ubc13-independent manner. Moreover, in HOIL-1   knockout mice and cells derived from these mice, NF-\u03baB signalling   induced by pro-inflammatory cytokines such as TNF-\u03b1 and IL-1\u03b2 was   suppressed, resulting in enhanced TNF-\u03b1-induced apoptosis in hepatocytes   of HOIL-1 knockout mice. These results indicate that LUBAC is involved   in the physiological regulation of the canonical NF-\u03baB activation   pathway through linear polyubiquitylation of NEMO. <\/p>\n<p class=\"mt25\"><span class=\"lineFrame\">URL<\/span> <a href=\"http:\/\/www.cellbio.med.osaka-u.ac.jp\/\" target=\"_blank\">http:\/\/www.cellbio.med.osaka-u.ac.jp\/<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"<p>Text in Japanese Click to enlarge 2009-1-11 Publish Nature Cell Biology 11,123-132, 2009 Nuclear factor-\u03baB (NF [&hellip;]<\/p>\n","protected":false},"author":1,"featured_media":1811,"parent":462,"menu_order":187,"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\/660"}],"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=660"}],"version-history":[{"count":6,"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/pages\/660\/revisions"}],"predecessor-version":[{"id":2379,"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/pages\/660\/revisions\/2379"}],"up":[{"embeddable":true,"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/pages\/462"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/media\/1811"}],"wp:attachment":[{"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/media?parent=660"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}