BTB proteins are substrate-specific adaptors in an SCF-like modular ubiquitin ligase containing CUL-3

Lai Xu, Yue Wei, Jerome Reboul, Philippe Vaglio, Tae Ho Shin, Marc Vidal, Stephen J. Elledge, J. Wade Harper

Research output: Contribution to journalArticle

329 Citations (Scopus)

Abstract

Programmed destruction of regulatory proteins, through the ubiquitin-proteasome system is a widely used mechanism for controlling signalling pathways. Cullins are proteins that function as scaffolds for modular ubiquitin ligases typified by the SCF (Skp1-Cul1-F-box) complex. The substrate selectivity of these E3 ligases is dictated by a specificity module that binds cullins. In the SCF complex, this module is composed of Skp1, which binds directly to Cul1, and a member of the F-box family of proteins. F-box proteins bind Skp1 through the F-box motif, and substrates by means of carboxy-terminal protein interaction domains. Similarly, Cul2 and Cul5 interact with BC-box-containing specificity factors through the Skp1-like protein elongin C2. Cul3 is required for embryonic development in mammals and Caenorhabditis elegans but its specificity module is unknown. Here we report the identification of a large family of BTB-domain proteins as substrate-specific adaptors for C. elegans CUL-3. Biochemical studies using the BTB protein MEL-26 and its genetic target MEI-1 (refs 12, 13) indicate that BTB proteins merge the functional properties of Skp1 and F-box proteins into a single polypeptide.

Original languageEnglish (US)
Pages (from-to)316-321
Number of pages6
JournalNature
Volume425
Issue number6955
DOIs
StatePublished - Sep 18 2003

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F-Box Proteins
Ligases
Ubiquitin
Cullin Proteins
Caenorhabditis elegans
F-Box Motifs
S-Phase Kinase-Associated Proteins
Proteins
Protein Interaction Domains and Motifs
Ubiquitin-Protein Ligases
Proteasome Endopeptidase Complex
Embryonic Development
Mammals
Peptides

ASJC Scopus subject areas

  • General

Cite this

Xu, L., Wei, Y., Reboul, J., Vaglio, P., Shin, T. H., Vidal, M., ... Harper, J. W. (2003). BTB proteins are substrate-specific adaptors in an SCF-like modular ubiquitin ligase containing CUL-3. Nature, 425(6955), 316-321. https://doi.org/10.1038/nature01985

BTB proteins are substrate-specific adaptors in an SCF-like modular ubiquitin ligase containing CUL-3. / Xu, Lai; Wei, Yue; Reboul, Jerome; Vaglio, Philippe; Shin, Tae Ho; Vidal, Marc; Elledge, Stephen J.; Harper, J. Wade.

In: Nature, Vol. 425, No. 6955, 18.09.2003, p. 316-321.

Research output: Contribution to journalArticle

Xu, L, Wei, Y, Reboul, J, Vaglio, P, Shin, TH, Vidal, M, Elledge, SJ & Harper, JW 2003, 'BTB proteins are substrate-specific adaptors in an SCF-like modular ubiquitin ligase containing CUL-3', Nature, vol. 425, no. 6955, pp. 316-321. https://doi.org/10.1038/nature01985
Xu, Lai ; Wei, Yue ; Reboul, Jerome ; Vaglio, Philippe ; Shin, Tae Ho ; Vidal, Marc ; Elledge, Stephen J. ; Harper, J. Wade. / BTB proteins are substrate-specific adaptors in an SCF-like modular ubiquitin ligase containing CUL-3. In: Nature. 2003 ; Vol. 425, No. 6955. pp. 316-321.
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