Identification of a novel Skp2-like mammalian protein containing F-box andleucine-rich repeats

The F-box protein Skp2 is important for S phase entry and binds to Skp1 and the cyclin A-Cdk2 complex, Here we report the cloning, analysis of genomic organization and characterization of a novel gene product related to Skp2 named FBL2, The human FBL2 gene was found to be a highly interrupted gene o f at least 126.6 kb located on chromosome 17 in close proximity to the TRAP 220 gene in a head-to-tail orientation. The predicted protein contains an F -box and six perfect C-terminal leucine-rich repeats. Similar to Skp2, this protein interacts with Skp1 and deletion of the F-box inhibits this associ ation, However, in contrast to Skp2, FBL2 was detected in non-proliferating hepatocytes and its expression increased in growth-arrested liver epitheli al cells. In addition, FBL2,vas localized primarily in the cytoplasm concen trated around the nucleus. Overall, our data indicate that although FBL2 sh ares strong structural homology with Skp2 as well as having a similar abili ty to associate with Skp1, these proteins likely play distinct roles and ta rget different substrates to the SCF complex. (C) 1999 Federation of Europe an Biochemical Societies.