A family of mammalian F-box proteins

Jeffrey T. Winston, Deanna M. Koepp, Zhu Cihui, Stephen J. Elledge, J. Wade Harper

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Abstract

Ubiquitin-mediated destruction of regulatory proteins is a frequent means of controlling progression through signaling pathways [1]. F-box proteins [2] are components of modular E3 ubiquitin protein ligases called SCFs, which function in phosphorylation-dependent ubiquitination ([3-5], reviewed in [6,7]). F-box proteins contain a carboxy-terminal domain that interacts with substrates and a 42-48 amino-acid F-box motif which binds to the protein Skp1 [2-4]. Skp1 binding links the F-box protein with a core ubiquitin ligase composed of the proteins Cdc53/Cul1, Rbx1 (also called Hrt1 and Roc1) and the E2 ubiquitin-conjugating enzyme Cdc34 [8-11]. The genomes of the budding yeast Saccharomyces cerevisiae and the nematode worm Caenorhabditis elegans contain, respectively, 16 and more than 60 F-box proteins [2,7]; in S. cerevisiae, the F-box proteins Cdc4, Grr1 and Met30 target cyclin-dependent kinase inhibitors, G1 cyclins and transcriptional regulators for ubiquitination ([3-5,8,10], reviewed in [6,7]). Only four mammalian F-box proteins (Cyclin F, Skp1, β-TRCP and NFB42) have been identified so far [2,12]. Here, we report the identification of a family of 33 novel mammalian F-box proteins. The large number of these proteins in mammals suggests that the SCF system controls a correspondingly large number of regulatory pathways in vertebrates. Four of these proteins contain a novel conserved motif, the F-box-associated (FBA) domain, which may represent a new protein-protein interaction motif. The identification of these genes will help uncover pathways controlled by ubiquitin-mediated proteolysis in mammals.

Original languageEnglish (US)
Pages (from-to)1180-1182
Number of pages3
JournalCurrent Biology
Volume9
Issue number20
DOIs
StatePublished - Oct 21 1999

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Winston, J. T., Koepp, D. M., Cihui, Z., Elledge, S. J., & Harper, J. W. (1999). A family of mammalian F-box proteins. Current Biology, 9(20), 1180-1182. https://doi.org/10.1016/S0960-9822(00)80021-4