Construction of polyubiquitin chain specific molecular probes and their applications to histopathologic examinations.
Project/Area Number |
23657075
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Research Category |
Grant-in-Aid for Challenging Exploratory Research
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Allocation Type | Multi-year Fund |
Research Field |
Structural biochemistry
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Research Institution | Gunma University |
Principal Investigator |
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Project Period (FY) |
2011 – 2012
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Project Status |
Completed (Fiscal Year 2012)
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Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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Keywords | ユビキチン / 炎症 / NF-κB / 細胞内シグナル伝達 / 分子プローブ / シグナル伝達 / 細胞・組織 / 酵素 / タンパク質 |
Research Abstract |
The ubiquitin system functions as a pivotal post-transcriptional modification in numerous cellular functions, including protein degradation and signal transduction. We identified that LUBAC (linear ubiquitin chain assembly complex) generates a novel type of Met1-linked linear polyubiquitin chain and specifically regulates the NF-κB pathway, which is a central signaling pathway for inflammatory and immune responses. In this study, we show that A20, a deubiquitinase, suppresses NF-κB activation by binding linear polyubiquitin via the C-terminal seventh zinc finger (ZF7), and we determined the crystal structures of A20 ZF7 in complex with linear diubiquitin. Importantly, we found that a tandem conjugate of three ZF7s is available as a high affinity molecular probe to detect linear poluubiquitin chain.
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Report
(3 results)
Research Products
(39 results)
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[Journal Article] Non-canonical UBA-UBL interaction mediates formation of linear ubiquitin chain assembly complex2012
Author(s)
Hirokazu Yagi, Kazuhiro Ishimoto, Takeshi Hiromoto, Hiroaki Fujita, Tsunehiro Mizushima, Yoshinori Uekusa, Maho Yagi-Utsumi, Eiji Kurimoto, Masanori Noda, Susumu Uchiyama, Fuminori Tokunaga, Kazuhiro Iwai, and Koichi Kato
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Journal Title
EMBO Rep
Volume: 13
Pages: 462-468
Related Report
Peer Reviewed
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[Journal Article] Backbone and side chain 1H, 13C, and 15N assignments of ubiquitin-like domain of human HOIL-1L, an essential component of linear ubiquitin chain assembly complex2012
Author(s)
Yoshinori Uekusa, Syunsuke Miura, Hiroaki Sasakawa, Eiji Kurimoto, Eri Sakata, Serve Oliver, Hirokazu Yagi, Fuminori Tokunaga,Kazuhiro Iwai, and Koichi Kato
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Journal Title
Biomol. NMR Assign.
Volume: 6
Pages: 177-180
Related Report
Peer Reviewed
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[Journal Article] A non-canonical UBA-UBL interaction forms the linear-ubiquitin-chain assembly complex.2012
Author(s)
H.Yagi, K.Ishimoto, T.Hiromoto, H.Fujita, T.Mizushima, Y.Uekusa, M.Yagi-Utsumi, E.Kurimoto, M.Noda, S.Uchiyama, F.Tokunaga, K. Iwai, and K.Kato
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Journal Title
EMBO Rep.
Volume: 13
Issue: 5
Pages: 462-468
DOI
Related Report
Peer Reviewed
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[Journal Article] Backbone and side chain ^1H, ^<13>C, and ^<15>N assignments of the ubiquitin-like domain of human HOIL-1L, an essential component of linear ubiquitin chain assembly complex2012
Author(s)
Y.Uekusa, S.Mimura, H.Sasakawa, E.Kurimoto, E.Sakata, S.Olivier, H.Yagi, F.Tokunaga, K.Iwai, K.Kato
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Journal Title
Biomol.NMR Assign.
Volume: (in press)
Issue: 2
Pages: 177-180
DOI
Related Report
Peer Reviewed
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[Journal Article] SHARPIN forms a linear ubiquitin ligase complex regulating NF-κB activity and apoptosis2011
Author(s)
Fumiyo Ikeda, Yonathan Lissanu Deribe, Sigrid S. Skanland, Benjamin Stieglitz, Caroline Grabbe, Sjoerd van WijK, Mirita Franz-Wachtel, Panchali Goswami, Vanja Nagy, Janos Terzic, Fuminori Tokunaga, Ariadne Androulidaki, Tomoko Nakagawa, Manolis Pasparakis, Kazuhiro Iwai, John P. Sundberg, Liliana Schaefer, Boris Macek, Katrin Rittinger, and Ivan Dikic
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Journal Title
Nature
Volume: 471
Pages: 637-641
Related Report
Peer Reviewed
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[Journal Article] Sharpin is a component of the NF-κB activating linear ubiquitin chain assembly complex2011
Author(s)
Tokunaga, F., Nakagawa, T., Nakahara, M., Saeki, Y., Taniguchi, M., Sakata, S., Tanaka, K., Nakano, H., Iwai, I.
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Journal Title
Nature
Volume: 471
Issue: 7340
Pages: 633-636
DOI
Related Report
Peer Reviewed
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