title: Ectopic expression of human Cdk2 and its yeast homolog, Ime2, is deleterious to Saccharomyces cerevisiae.
abstract: Entry into and precise progression through the cell cycle depends on the sequential expression and activation of cyclin dependent kinases (CDK). In accord, CDK dysregulation is a hallmark of many cancers. The function of Cdk2 is still an enigma as in vitro studies revealed that it is required for S phase-entry, whereas in vivo studies showed that Cdk2 is not an essential gene. Moreover, unlike other Cdks, or its cyclin E regulator, Cdk2-overexpressing tumors were reported only in one type of tumor. In this report we used budding yeast as a tool to explore Cdk2 function. We showed that hCdk2 promoted S phase in cells carrying a temperature-sensitive mutation in yCDK1, albeit, only when expressed at low or moderate levels. Overexpression of hCdk2 resulted in a defect in the G1 to S transition and a reduction in viability. The same phenotypes were observed in cells overexpressing its yeast functional homolog, Ime2, which is a meiosis-specific CDK-like kinase. A genetic interaction with the DNA damage checkpoint was demonstrated by showing an increased toxicity of hCdk2 and Ime2 in RAD53-deleted cells, and delayed Rad53 activation in response to MMS treatment in cells overexpressing hCdk2 or Ime2.
authors.affiliation: Department of Biology, Technion, Israel Institute of Technology, Haifa, Israel.
authors.forename: Moran
authors.initials: M
authors.lastname: Szwarcwort-Cohen
authors.forename: Vyacheslav
authors.initials: V
authors.lastname: Gurevich
authors.forename: Shira
authors.initials: S
authors.lastname: Sagee
authors.forename: Yona
authors.initials: Y
authors.lastname: Kassir
mesh_terms: D016203:CDC2 Protein Kinase / Q000378:metabolism; D017489:CDC28 Protein Kinase, S cerevisiae / Q000378:metabolism / Q000502:physiology; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D064447:Checkpoint Kinase 2; D051357:Cyclin-Dependent Kinase 2 / Q000235:genetics / Q000378:metabolism*; D004249:DNA Damage; D016193:G1 Phase; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008540:Meiosis; D010641:Phenotype; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D016196:S Phase; D012441:Saccharomyces cerevisiae / Q000201:enzymology*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; D047908:Intracellular Signaling Peptides and Proteins; D029701:Saccharomyces cerevisiae Proteins; D064447:Checkpoint Kinase 2; C064979:IME2 protein, S cerevisiae; D017346:Protein Serine-Threonine Kinases; D016203:CDC2 Protein Kinase; D017489:CDC28 Protein Kinase, S cerevisiae; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2; C067022:RAD53 protein, S cerevisiae