1. The Scripps Research Institute, Department of Molecular Biology, 10550 North Torrey Pines Road, La Jolla, California 92037, USA
2. Present addresses: Centre de Recherches en Biochimie Macromoléculaire—CNRS-UPR1086, 1919 Route de Mende, 34293 Montpellier, France (M.C.M.); University of California Irvine, Department of Biological Chemistry, Irvine, California 92697-1700, USA (P.K.); Gemin X Biotechnologies Inc., CP/PO Box 477, Place du Parc, Montreal, Quebec, Canada H2W 2M9 (M.H.W.).

Correspondence to: Steven I. Reed¹ Correspondence and requests for materials should be addressed to S.I.R. (Email: sreed@scripps.edu).

Abstract

Cks proteins are small evolutionarily conserved proteins that interact genetically and physically with cyclin-dependent kinases. However, in spite of a large body of genetic, biochemical and structural research, no compelling unifying model of their functions has emerged^{1, 2}. Here we show, by investigating the essential role of Cks1 in Saccharomyces cerevisiae, that the protein is primarily involved in promoting mitosis by modulating the transcriptional activation of the APC/C protein–ubiquitin ligase activator Cdc20. Cks1 is required for both the periodic dissociation of Cdc28 kinase from the CDC20 promoter and the periodic association of the proteasome with the promoter. We propose that the essential role of Cks1 is to recruit the proteasome to, and/or dissociate the Cdc28 kinase from, the CDC20 promoter, thus facilitating transcription by remodelling transcriptional complexes or chromatin associated with the CDC20 gene.