Occurrence of a putative SCF ubiquitin ligase complex in Drosophila

Many proteins are targeted to proteasome degradation by a family of E3 ubiq uitin ligases, termed SCF complexes, that link substrate proteins to an E2 ubiquitin-conjugating enzyme. SCFs are composed of three core proteins-Skp1 , Cdc53/Cul1, Rbx1/Hrt1-and a substrate specific F-box protein. We have ide ntified in Drosophila melanogaster the closest homologues to the human comp onents of the SCFbeta TrCP complex and the E2 ubiquitin-conjugating enzyme UbcH5. We show that putative Drosophila SCF core subunits dSkpA and dRbx1 b oth interact directly with dCu11 and the F-box protein Slmb. We also descri be the direct interaction of the UbcH5 related protein LTbcD1 with dCu11 an d Slmb. In addition, a functional complementation test performed on a Sacch aromyces cerevisiae Hrt1p-deficient mutant showed that Drosophila Rbx1 is a ble to restore the yeast cells viability. Our results suggest that dRbx1, d SkpA, dCullin1, and Slimb proteins are components of a Drosophila SCF compl ex that functions in combination with the ubiquitin conjugating enzyme LTbc D1. (C) 2001 Academic Press.