@article{a0c348aef7cd491fae83b99a348eb48c,
title = "BTB proteins are substrate-specific adaptors in an SCF-like modular ubiquitin ligase containing CUL-3",
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.",
author = "Lai Xu and Yue Wei and Jerome Reboul and Philippe Vaglio and Shin, {Tae Ho} and Marc Vidal and Elledge, {Stephen J.} and Harper, {J. Wade}",
note = "Funding Information: Acknowledgements We are grateful to the C. elegans Genetics Centre (funded by the NIH National Centre for Research Resources) for providing strains. We thank R. Fischer for generation of the monoclonal anti-MEL-26 antibody, P. G{\"o}nczy for introducing L.P. to C. elegans and for sharing material and reagents, P. Weissert for help with worm liquid cultures, J. M. Bellanger and I. Sumara for suggestions, P. Wiget for help with microscopy, and P. G{\"o}nczy for critical reading of the manuscript. L.P. was supported by a Long-Term Fellowship from the Federation of European Biochemical Societies (FEBS) and a Fellowship from Roche, T.K. by a predoctoral fellowship from the American Heart Association, J.H.W. by an NIH Molecular Biology Training Grant, P.E.M. by grants from the Canadian Institutes of Health Research and the Alberta Heritage Foundation for Medical Research, B.B. by the NIH and M.P. by the ETHZ and the Swiss National Science Foundation. Funding Information: 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.",
year = "2003",
month = sep,
day = "18",
doi = "10.1038/nature01985",
language = "English (US)",
volume = "425",
pages = "316--321",
journal = "Nature",
issn = "0028-0836",
publisher = "Nature Publishing Group",
number = "6955",
}