Ubiquitin-dependent degradation of IκBα is mediated by a ubiquitin ligase Skp1/Cul 1/F-box protein FWD1

Shigetsugu Hatakeyama, Masatoshi Kitagawa, Keiko Nakayama, Michiko Shirane, Masaki Matsumoto, Kimihiko Hattori, Hideaki Higashi, Hiroyasu Nakano, Ko Okumura, Kazunori Onoé, Robert A. Good, Kei Ichi Nakayama

研究成果: ジャーナルへの寄稿記事

168 引用 (Scopus)

抄録

Activation of the transcription factor nuclear factor kappa B (NF-κB) is controlled by proteolysis of its inhibitory subunit (IκB) via the ubiquitin-proteasome pathway. Signal-induced phosphorylation of IκBα by a large multisubunit complex containing IκB kinases is a prerequisite for ubiquitination. Here, we show that FWD1 (a mouse homologue of Slimb/βTrCP), a member of the F-box/WD40-repeat proteins, is associated specifically with IκBα only when IκBα is phosphorylated. The introduction of FWD1 into cells significantly promotes ubiquitination and degradation of IκBα in concert with IκB kinases, resulting in nuclear translocation of NF-κB. In addition, FWD1 strikingly evoked the ubiquitination of IκBα in the in vitro system. In contrast, a dominant-negative form of FWD1 inhibits the ubiquitination, leading to stabilization of IκBα. These results suggest that the substrate-specific degradation of IκBα is mediated by a Skp1/Cull 1/F-box protein (SCF) FWD1 ubiquitin-ligase complex and that FWD1 serves as an intracellular receptor for phosphorylated IκBα. Skp1/Cullin/F-box protein FWD1 might play a critical role in transcriptional regulation of NF- κB through control of IκB protein stability.

元の言語英語
ページ(範囲)3859-3863
ページ数5
ジャーナルProceedings of the National Academy of Sciences of the United States of America
96
発行部数7
DOI
出版物ステータス出版済み - 3 30 1999

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F-Box Proteins
Ubiquitination
Ligases
Ubiquitin
SKP Cullin F-Box Protein Ligases
Phosphotransferases
NF-kappa B
Protein Stability
Proteasome Endopeptidase Complex
Proteolysis
Transcription Factors
Phosphorylation
Proteins

All Science Journal Classification (ASJC) codes

  • General

これを引用

Ubiquitin-dependent degradation of IκBα is mediated by a ubiquitin ligase Skp1/Cul 1/F-box protein FWD1. / Hatakeyama, Shigetsugu; Kitagawa, Masatoshi; Nakayama, Keiko; Shirane, Michiko; Matsumoto, Masaki; Hattori, Kimihiko; Higashi, Hideaki; Nakano, Hiroyasu; Okumura, Ko; Onoé, Kazunori; Good, Robert A.; Nakayama, Kei Ichi.

:: Proceedings of the National Academy of Sciences of the United States of America, 巻 96, 番号 7, 30.03.1999, p. 3859-3863.

研究成果: ジャーナルへの寄稿記事

Hatakeyama, Shigetsugu ; Kitagawa, Masatoshi ; Nakayama, Keiko ; Shirane, Michiko ; Matsumoto, Masaki ; Hattori, Kimihiko ; Higashi, Hideaki ; Nakano, Hiroyasu ; Okumura, Ko ; Onoé, Kazunori ; Good, Robert A. ; Nakayama, Kei Ichi. / Ubiquitin-dependent degradation of IκBα is mediated by a ubiquitin ligase Skp1/Cul 1/F-box protein FWD1. :: Proceedings of the National Academy of Sciences of the United States of America. 1999 ; 巻 96, 番号 7. pp. 3859-3863.
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T1 - Ubiquitin-dependent degradation of IκBα is mediated by a ubiquitin ligase Skp1/Cul 1/F-box protein FWD1

AU - Hatakeyama, Shigetsugu

AU - Kitagawa, Masatoshi

AU - Nakayama, Keiko

AU - Shirane, Michiko

AU - Matsumoto, Masaki

AU - Hattori, Kimihiko

AU - Higashi, Hideaki

AU - Nakano, Hiroyasu

AU - Okumura, Ko

AU - Onoé, Kazunori

AU - Good, Robert A.

AU - Nakayama, Kei Ichi

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