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]Bai C Sen P Hofman K Ma L Goebel M Harper W Elledge S Skp1 connects cell cycle regulators to the ubiquitin proteolysis machinery through a novel motif, the F-box.Cell. 1996; 86: 263-274Abstract Full Text Full Text PDF PubMed Scopus (932) Google Scholar]. Some F-box proteins have been shown to be critical for the controlled degradation of cellular regulatory proteins [2Patton E Willems A Tyers M Combinatorial control in ubiquitin-dependent proteolysis: don't Skp the F-box hypothesis.Trends Genet. 1998; 14: 6-14Abstract Full Text Full Text PDF Scopus (439) Google Scholar, 3Koepp D Harper JW Elledge SJ How the cyclin became a cyclin: regulated proteolysis in the cell cycle.Cell. 1999; 97: 431-433Abstract Full Text Full Text PDF PubMed Scopus (384) Google Scholar]. 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 [2Patton E Willems A Tyers M Combinatorial control in ubiquitin-dependent proteolysis: don't Skp the F-box hypothesis.Trends Genet. 1998; 14: 6-14Abstract Full Text Full Text PDF Scopus (439) Google Scholar, 4Kumar A Paietta JV An additional role for the F-box motif: gene regulation within the Neurospora crassa sulfur control network.Proc Natl Acad Sci USA. 1998; 95: 2417-2422Crossref Scopus (34) Google Scholar] 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.