The SCF ubiquitin ligase protein Slimb regulates centrosome duplication inDrosophila

The duplication of the centrosome is a key event in the cell-division cycle . Although defects in centrosome duplication are thought to contribute to g enomic instability [1-3] and are a hallmark of certain transformed cells an d human cancer [4-6], the mechanism responsible for centrosome duplication is not understood. Recent experiments have established that centrosome dupl ication requires the activity of cyclin-dependent kinase 2 (Cdk2) and cycli ns E and A [7-9], The stability of cyclin E is regulated by the ubiquitin l igase SCF, which is a protein complex composed of Skp1, Cdc53 (Cullin) and F-box proteins [10-12], The Skp1 and Cullin components have been detected o n mammalian centrosomes, and shown to be essential for centrosome duplicati on and separation in Xenopus [13]. Here, we report that Slimb, an F-box pro tein that targets proteins to the SCF complex [14,15], plays a role in limi ting centrosome replication. We found that, in the fruit fly Drosophila, th e hypomorphic mutation slimb(crd) causes the appearance of additional centr osomes and mitotic defects in mutant larval neuroblasts.