Satoshi AsanoJung Eun ParkKrisada SakchaisriLi Rong YuSukgil SongPorntip SupavilaiTimothy D. VeenstraKyung S. LeeNational Cancer InstituteMahidol UniversityNational Cancer Institute at FrederickChungbuk National University2018-06-212018-06-212005-06-15EMBO Journal. Vol.24, No.12 (2005), 2194-2204026141892-s2.0-21844458914https://repository.li.mahidol.ac.th/handle/20.500.14594/16333In eukaryotes, entry into mitosis is induced by cyclin B-bound Cdk1, which is held in check by the protein kinase, Wee1. In budding yeast, Swe1 (Wee1 ortholog) is targeted to the bud neck through Hsl1 (Nim1-related kinase) and its adaptor Hsl7, and is hyperphosphorylated prior to ubiquitin-mediated degradation. Here, we show that Hsl1 and Hsl7 are required for proper localization of Cdc5 (Polo-like kinase homolog) to the bud neck and Cdc5-dependent Swe1 phosphorylation. Mitotic cyclin (Clb2)-bound Cdc28 (Cdk1 homolog) directly phosphorylated Swe1 and this modification served as a priming step to promote subsequent Cdc5-dependent Swe1 hyperphosphorylation and degradation. Clb2-Cdc28 also facilitated Cdc5 localization to the bud neck through the enhanced interaction between the Clb2-Cdc28-phosphorylated Swe1 and the polo-box domain of Cdc5. We propose that the concerted action of Cdc28/Cdk1 and Cdc5/Polo on their common substrates is an evolutionarily conserved mechanism that is crucial for effectively triggering mitotic entry and other critical mitotic events. © 2005 European Molecular Biology Organization | All Rights Reserved.Mahidol UniversityBiochemistry, Genetics and Molecular BiologyImmunology and MicrobiologyNeuroscienceArticleSCOPUS10.1038/sj.emboj.7600683