title: Identification of a family of human F-box proteins.
abstract: F-box proteins are an expanding family of eukaryotic proteins characterized by an approximately 40 aminoacid motif, the F box (so named because cyclin F was one of the first proteins in which this motif was identified) [1]. Some F-box proteins have been shown to be critical for the controlled degradation of cellular regulatory proteins [2] [3]. In fact, F-box proteins are one of the four subunits of ubiquitin protein ligases called SCFs. The other three subunits are the Skp1 protein; one of the cullin proteins (Cul1 in metazoans and Cdc53 or Cul A in the yeast Saccharomyces cerevisiae); and the recently identified Roc1 protein (also called Rbx1 or Hrt1). SCF ligases bring ubiquitin conjugating enzymes (either Ubc3 or Ubc4) to substrates that are specifically recruited by the different F-box proteins. The need for high substrate specificity and the large number of known F-box proteins in yeast and worms [2] [4] suggest the existence of a large family of mammalian F-box proteins. Using Skp1 as a bait in a yeast two-hybrid screen and by searching DNA databases, we identified a family of 26 human F-box proteins, 25 of which were novel. Some of these proteins contained WD-40 domains or leucine-rich repeats; others contained either different protein-protein interaction modules or no recognizable motifs. We have named the F-box proteins that contain WD-40 domains Fbws, those containing leucine-rich repeats, Fbls, and the remaining ones Fbxs. We have further characterized representative members of these three classes of F-box proteins.
authors.affiliation: Department of Pathology, Kaplan Comprehensive Cancer Center, MSB 548, New York University School of Medicine 550 First Avenue, New York, New York, 10016, USA.
authors.forename: C
authors.initials: C
authors.lastname: Cenciarelli
authors.forename: D S
authors.initials: DS
authors.lastname: Chiaur
authors.forename: D
authors.initials: D
authors.lastname: Guardavaccaro
authors.forename: W
authors.initials: W
authors.lastname: Parks
authors.forename: M
authors.initials: M
authors.lastname: Vidal
authors.forename: M
authors.initials: M
authors.lastname: Pagano
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D010453:Peptide Synthases / Q000378:metabolism; D011506:Proteins / Q000737:chemistry* / Q000145:classification* / Q000235:genetics; D044843:SKP Cullin F-Box Protein Ligases; D017386:Sequence Homology, Amino Acid; D020798:Two-Hybrid System Techniques; D014452:Ubiquitins / Q000378:metabolism
chemical_list: D011506:Proteins; D014452:Ubiquitins; D044843:SKP Cullin F-Box Protein Ligases; D010453:Peptide Synthases