Résumé
Abstract only Cks proteins are physical interactors of cyclin‐dependent kinases that play a central role in eukaryotic cell cycle progression, in both activation and degradation signalling pathways. Functionally, these small proteins stabilize cdk‐cyclin complexes and behave as adaptors through recruitment of a variety of proteins, including phosphoprotein regulators Wee1, Myt1 and Cdc25, the Skp2 ubiquitin ligase component, and proteasomal subunits. In budding yeast, Cks1p is implicated in transcriptional regulation through association with transcriptional loci, where it recruits proteasomal subunits. We report a novel interaction between S.cerevisiae Cks1p and ubiquitin and provide evidence that it differs altogether from interactions described to date between ubiquitin and proteins harbouring ubiquitin‐binding domains in both its affinity and the mode of interaction. Cks1p interacts specifically with monoubiquitin and tetraubiquitin in a nonconventional fashion which involves the major alpha helix of ubiquitin, instead of beta sheets B3 and B4 and the hydrophobic pocket centered around ILE44. This is not only the first report of a physical interaction between Cks1p and ubiquitin, but also the first time the alpha helix of ubiquitin is directly involved in an interaction with a protein partner. Our finding provides novel insights into both the function of Cks proteins and the mechanisms of ubiquitin recognition.