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j.celrep.2018.03.112.pdf | 4.41 MB | Adobe PDF | 見る/開く |
タイトル: | Cooperative Domain Formation by Homologous Motifs in HOIL-1L and SHARPIN Plays A Crucial Role in LUBAC Stabilization |
著者: | Fujita, Hiroaki https://orcid.org/0000-0003-1465-6425 (unconfirmed) Tokunaga, Akira Shimizu, Satoshi Whiting, Amanda L. Aguilar-Alonso, Francisco Takagi, Kenji Walinda, Erik https://orcid.org/0000-0003-1882-6401 (unconfirmed) Sasaki, Yoshiteru Shimokawa, Taketo Mizushima, Tsunehiro Ohki, Izuru https://orcid.org/0000-0002-0667-5936 (unconfirmed) Ariyoshi, Mariko Tochio, Hidehito https://orcid.org/0000-0003-3843-3330 (unconfirmed) Bernal, Federico Shirakawa, Masahiro Iwai, Kazuhiro https://orcid.org/0000-0001-5620-5951 (unconfirmed) |
著者名の別形: | 藤田, 宏明 徳永, 暉 清水, 覚司 高木, 賢治 佐々木, 義輝 下川, 岳人 水島, 恒裕 大木, 出 有吉, 眞理子 杤尾, 豪人 白川, 昌宏 岩井, 一宏 |
キーワード: | linear ubiquitin chains LUBAC LUBAC-tethering motif HOIP HOIL-1L SHARPIN ubiquitin-like domain ubiquitin-associated domain cancer |
発行日: | 24-Apr-2018 |
出版者: | Elsevier BV |
誌名: | Cell Reports |
巻: | 23 |
号: | 4 |
開始ページ: | 1192 |
終了ページ: | 1204 |
抄録: | The linear ubiquitin chain assembly complex (LUBAC) participates in inflammatory and oncogenic signaling by conjugating linear ubiquitin chains to target proteins. LUBAC consists of the catalytic HOIP subunit and two accessory subunits, HOIL-1L and SHARPIN. Interactions between the ubiquitin-associated (UBA) domains of HOIP and the ubiquitin-like (UBL) domains of two accessory subunits are involved in LUBAC stabilization, but the precise molecular mechanisms underlying the formation of stable trimeric LUBAC remain elusive. We solved the co-crystal structure of the binding regions of the trimeric LUBAC complex and found that LUBAC-tethering motifs (LTMs) located N terminally to the UBL domains of HOIL-1L and SHARPIN heterodimerize and fold into a single globular domain. This interaction is resistant to dissociation and plays a critical role in stabilizing trimeric LUBAC. Inhibition of LTM-mediated HOIL-1L/SHARPIN dimerization profoundly attenuated the function of LUBAC, suggesting LTM as a superior target of LUBAC destabilization for anticancer therapeutics. |
記述: | がんを誘発する酵素の新たなタンパク質間相互作用を解明 --抗がん剤の新たなターゲットを発見--. 京都大学プレスリリース. 2018-04-25. |
著作権等: | © 2018 The Author(s). This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
URI: | http://hdl.handle.net/2433/230872 |
DOI(出版社版): | 10.1016/j.celrep.2018.03.112 |
PubMed ID: | 29694895 |
関連リンク: | https://www.kyoto-u.ac.jp/ja/research-news/2018-04-25 |
出現コレクション: | 学術雑誌掲載論文等 |
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