Identification of a family of human F-box proteins

F-box proteins are an expanding family of eukaryotic proteins characterized by an approximately 40 amino-acid 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 Rod 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.