Molecular clearance of ataxin-3 is regulated by a mammalian E4

Masaki Matsumoto, Masayoshi Yada, Shigetsugu Hatakeyama, Hiroshi Ishimoto, Teiichi Tanimura, Shoji Tsuji, Akira Kakizuka, Masatoshi Kitagawa, Keiichi I. Nakayama

研究成果: ジャーナルへの寄稿記事

113 引用 (Scopus)

抄録

Insoluble aggregates of polyglutamine-containing proteins are usually conjugated with ubiquitin in neurons of individuals with polyglutamine diseases. We now show that ataxin-3, in which the abnormal expansion of a polyglutamine tract is responsible for spinocerebellar ataxia type 3 (SCA3), undergoes ubiquitylation and degradation by the proteasome. Mammalian E4B (UFD2a), a ubiquitin chain assembly factor (E4), copurified with the polyubiquitylation activity for ataxin-3. E4B interacted with, and thereby mediated polyubiquitylation of, ataxin-3. Expression of E4B promoted degradation of a pathological form of ataxin-3. In contrast, a dominant-negative mutant of E4B inhibited degradation of this form of ataxin-3, resulting in the formation of intracellular aggregates. In a Drosophila model of SCA3, expression of E4B suppressed the neurodegeneration induced by an ataxin-3 mutant. These observations suggest that E4 is a rate-limiting factor in the degradation of pathological forms of ataxin-3, and that targeted expression of E4B is a potential gene therapy for SCA3.

元の言語英語
ページ(範囲)659-669
ページ数11
ジャーナルEMBO Journal
23
発行部数3
DOI
出版物ステータス出版済み - 2 11 2004

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Machado-Joseph Disease
Degradation
Ubiquitin
Gene therapy
Ubiquitination
Proteasome Endopeptidase Complex
Ataxin-3
Genetic Therapy
Drosophila
Neurons
polyglutamine
Proteins

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

これを引用

Molecular clearance of ataxin-3 is regulated by a mammalian E4. / Matsumoto, Masaki; Yada, Masayoshi; Hatakeyama, Shigetsugu; Ishimoto, Hiroshi; Tanimura, Teiichi; Tsuji, Shoji; Kakizuka, Akira; Kitagawa, Masatoshi; Nakayama, Keiichi I.

:: EMBO Journal, 巻 23, 番号 3, 11.02.2004, p. 659-669.

研究成果: ジャーナルへの寄稿記事

Matsumoto, M, Yada, M, Hatakeyama, S, Ishimoto, H, Tanimura, T, Tsuji, S, Kakizuka, A, Kitagawa, M & Nakayama, KI 2004, 'Molecular clearance of ataxin-3 is regulated by a mammalian E4', EMBO Journal, 巻. 23, 番号 3, pp. 659-669. https://doi.org/10.1038/sj.emboj.7600081
Matsumoto M, Yada M, Hatakeyama S, Ishimoto H, Tanimura T, Tsuji S その他. Molecular clearance of ataxin-3 is regulated by a mammalian E4. EMBO Journal. 2004 2 11;23(3):659-669. https://doi.org/10.1038/sj.emboj.7600081
Matsumoto, Masaki ; Yada, Masayoshi ; Hatakeyama, Shigetsugu ; Ishimoto, Hiroshi ; Tanimura, Teiichi ; Tsuji, Shoji ; Kakizuka, Akira ; Kitagawa, Masatoshi ; Nakayama, Keiichi I. / Molecular clearance of ataxin-3 is regulated by a mammalian E4. :: EMBO Journal. 2004 ; 巻 23, 番号 3. pp. 659-669.
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