title: Characterisation of human cdc2 lysine 33 mutations expressed in the fission yeast Schizosaccharomyces pombe.
abstract: The mammalian p34cdc2 protein kinase, a universal cell cycle regulator, complements cdc2/CDC28 temperature-sensitive mutations in yeasts. We report the biochemical characterisation of two substitutions of human cdc2 at lysine 33, a residue involved in nucleotide binding, that differently alter the fission yeast cell cycle. K33A-hscdc2 and K33R-hscdc2 mutants are both catalytically inactive, but overexpression of K33R-cdc2 is lethal while K33A-cdc2 is not. We show that human K33R-cdc2 acts as a dominant negative allele that associates yeast cdc13/cyclinB and therefore renders endogeneous Schizosaccharomyces pombe cdc2 unactivatable. These results are discussed on the light of the molecular modeling of the mutants in the cdc2 model structure.
authors.affiliation: Laboratoire de Pharmacologie et de Toxicologie Fondamentales du CNRS, Université Paul Sabatier, Toulouse, France.
authors.forename: D
authors.initials: D
authors.lastname: Leroy
authors.forename: C
authors.initials: C
authors.lastname: Birck
authors.forename: P
authors.initials: P
authors.lastname: Brambilla
authors.forename: J P
authors.initials: JP
authors.lastname: Samama
authors.forename: B
authors.initials: B
authors.lastname: Ducommun
mesh_terms: D001622:Betaine / Q000737:chemistry* / Q000378:metabolism; D016203:CDC2 Protein Kinase / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D002452:Cell Count; D002453:Cell Cycle; D016213:Cyclins / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D016296:Mutagenesis; D011494:Protein Kinases / Q000737:chemistry / Q000378:metabolism; D012568:Schizosaccharomyces / Q000166:cytology / Q000378:metabolism*
chemical_list: D016213:Cyclins; D001622:Betaine; D011494:Protein Kinases; D016203:CDC2 Protein Kinase