title: Molecular control of the Wee1 regulatory pathway by the SAD kinase Cdr2.
abstract: Cell growth and division are tightly coordinated to maintain cell size constant during successive cell cycles. In Schizosaccharomyces pombe, the SAD kinase Cdr2 regulates the cell size at division and the positioning of the division plane. Cdr2 forms nodes on the medial cortex containing factors that constitute an inhibitory pathway for Wee1. This pathway is regulated by polar gradients of the DYRK kinase Pom1, and involves a direct inhibitor of Wee1, the SAD kinase Cdr1. Cdr2 also interacts with the anillin Mid1, which defines the division plane, and with additional components of the medial cortical nodes, including Blt1, which participate in the mitotic-promoting and cytokinetic functions of nodes. Here, we show that the interaction of Cdr2 with Wee1 and Mid1 requires the UBA domain of Cdr2, which is necessary for its kinase activity. In contrast, Cdr1 associates with the C-terminus of Cdr2, which is composed of basic and KA-1 lipid-binding domains. Mid1 also interacts with the C-terminus of Cdr2 and might bridge the N- and C-terminal domains, whereas Blt1 associates with the central spacer region. We propose that the association of Cdr2 effectors with different domains might constrain Cdr1 and Wee1 spatially to promote Wee1 inhibition upon Cdr2 kinase activation.
authors.affiliation: Institut Curie, Centre de Recherche, PSL Research University, Paris F-75248, France CNRS UMR144, Paris F-75248, France.
authors.forename: Mercè
authors.initials: M
authors.lastname: Guzmán-Vendrell
authors.affiliation: Institut Curie, Centre de Recherche, PSL Research University, Paris F-75248, France CNRS UMR144, Paris F-75248, France.
authors.forename: Sergio A
authors.initials: SA
authors.lastname: Rincon
authors.affiliation: Institut Curie, Centre de Recherche, PSL Research University, Paris F-75248, France Laboratory of Mass Spectrometry and Proteomics, Paris F-75248, France.
authors.forename: Florent
authors.initials: F
authors.lastname: Dingli
authors.affiliation: Institut Curie, Centre de Recherche, PSL Research University, Paris F-75248, France Laboratory of Mass Spectrometry and Proteomics, Paris F-75248, France.
authors.forename: Damarys
authors.initials: D
authors.lastname: Loew
authors.affiliation: Institut Curie, Centre de Recherche, PSL Research University, Paris F-75248, France CNRS UMR144, Paris F-75248, France Anne.paoletti@curie.fr.
authors.forename: Anne
authors.initials: A
authors.lastname: Paoletti
mesh_terms: D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D048429:Cell Size; D004271:DNA, Fungal / Q000235:genetics; D008938:Mitosis / Q000235:genetics; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation / Q000235:genetics; D011485:Protein Binding; D011494:Protein Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*; D012568:Schizosaccharomyces / Q000235:genetics*; D029702:Schizosaccharomyces pombe Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*
chemical_list: C000595353:Blt1 protein, S pombe; D018797:Cell Cycle Proteins; D004271:DNA, Fungal; C489694:Mid1 protein, S pombe; D009687:Nuclear Proteins; D029702:Schizosaccharomyces pombe Proteins; D011494:Protein Kinases; C112212:Pom1 protein, S pombe; C080364:cdr1 protein, S pombe; C068689:wee1 protein, S pombe; D011505:Protein-Tyrosine Kinases; C542567:Cdr2 protein, S pombe; D017346:Protein Serine-Threonine Kinases
keywords: Cdr2; Cell cycle; Cell division; Cytokinesis; Mitosis; Wee1