BTB proteins are substrate-specific adaptors in an SCF-like modular ubiquitin ligase containing CUL-3 (original) (raw)
- Letter
- Published: 03 September 2003
- Yue Wei2 na1,
- Jerome Reboul5 nAff9,
- Philippe Vaglio5,
- Tae-Ho Shin4,
- Marc Vidal5,
- Stephen J. Elledge1,3 nAff8 &
- …
- J. Wade Harper1,2 nAff7
Nature volume 425, pages 316–321 (2003)Cite this article
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Abstract
Programmed destruction of regulatory proteins through the ubiquitin–proteasome system is a widely used mechanism for controlling signalling pathways1,2. Cullins3 are proteins that function as scaffolds for modular ubiquitin ligases typified by the SCF (Skp1–Cul1–F-box) complex4,5,6. 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 proteins4,5,6,7. F-box proteins bind Skp1 through the F-box motif7, and substrates by means of carboxy-terminal protein interaction domains1,2,5. 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 elegans8,9,10 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.
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Acknowledgements
We thank M. Peter for anti-CUL-3 and anti-MEL-26 antibodies. This work was supported by an NIH grant (to J.W.H. and S.J.E.), the Welch Foundation (to J.W.H.), and the National Human Genome Research Institute (to M.V.). Y.W. was supported by a Department of Defense predoctoral fellowship. S.J.E. is an investigator of the Howard Hughes Medical Institute.
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Author notes
- J. Wade Harper
Present address: Department of Pathology, Harvard Medical School, 200 Longwood Avenue, Boston, Massachusetts, 02115, USA - Stephen J. Elledge
Present address: Center for Genetics and Genomics, Department of Genetics, Howard Hughes Medical Institute, Harvard Medical School, 200 Longwood Avenue, Boston, Massachusetts, 02115, USA - Jerome Reboul
Present address: INSERM Unite 119, Institut Paoli Calmette, 13009, Marseille, France - Lai Xu and Yue Wei: These authors contributed equally to this work
Authors and Affiliations
- Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, Texas, 77030, USA
Lai Xu, Stephen J. Elledge & J. Wade Harper - Department of Molecular Physiology and Biophysics, Baylor College of Medicine, One Baylor Plaza, Houston, Texas, 77030, USA
Yue Wei & J. Wade Harper - Howard Hughes Medical Institute, Baylor College of Medicine, One Baylor Plaza, Houston, Texas, 77030, USA
Stephen J. Elledge - Department of Cell and Molecular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, Texas, 77030, USA
Tae-Ho Shin - Dana Farber Cancer Institute, Department of Genetics, Harvard Medical School, Boston, Massachusetts, 02115, USA
Jerome Reboul, Philippe Vaglio & Marc Vidal
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- Lai Xu
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Xu, L., Wei, Y., Reboul, J. et al. BTB proteins are substrate-specific adaptors in an SCF-like modular ubiquitin ligase containing CUL-3.Nature 425, 316–321 (2003). https://doi.org/10.1038/nature01985
- Received: 15 July 2003
- Accepted: 14 August 2003
- Published: 03 September 2003
- Issue Date: 18 September 2003
- DOI: https://doi.org/10.1038/nature01985