title: Transcription factor E2F and cyclin E-Cdk2 complex cooperate to induce chromosomal DNA replication in Xenopus oocytes.
abstract: Although no chromosomal DNA replication actually occurs during Xenopus oocyte maturation, the capability develops during the late meiosis I (MI) phase in response to progesterone. This ability, however, is suppressed by Mos proteins and maturation/mitosis promoting factor during the second meiosis phase (meiosis II; MII) until fertilization. Inhibition of RNA synthesis by actinomycin D during early MI prevented induction of the replication ability, but did not interfere with initiation of the meiotic cell cycle progression characterized by oscillation of the maturation/mitosis promoting factor activity and germinal vesicle breakdown. Microinjection of recombinant proteins such as dominant-negative E2F or universal Cdk inhibitors, p21 and p27, but not wild type human E2F-1 or Cdk4-specific inhibitor, p19, into maturing oocytes during MI abolished induction of the DNA replication ability. Co-injection of human E2F-1 and cyclin E proteins into immature oocytes allowed them to initiate DNA replication even in the absence of progesterone treatment. Injection of cyclin E alone, which was sufficient to activate endogenous Cdk2 kinase, failed to induce DNA replication. Moreover, the activation of Cdk2 was not affected under the conditions where DNA replication was blocked by actinomycin D. Thus, like somatic cells, both activities of E2F and cyclin E-Cdk2 complex are required for induction of the DNA replication ability in maturing Xenopus oocytes, and enhancement of both activities enables oocytes to override DNA-replication inhibitory mechanisms that specifically lie in maturing oocytes.
authors.affiliation: Graduate School of Biological Sciences, Nara Institute of Science and Technology, 8916-5 Takayama, Ikoma, Nara 630-0101, Japan.
authors.forename: E
authors.initials: E
authors.lastname: Akamatsu
authors.forename: T
authors.initials: T
authors.lastname: Tanaka
authors.forename: J Y
authors.initials: JY
authors.lastname: Kato
mesh_terms: D000818:Animals; D042846:CDC2-CDC28 Kinases; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D002478:Cells, Cultured; D002875:Chromosomes / Q000378:metabolism; D019927:Cyclin E / Q000378:metabolism*; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases / Q000378:metabolism*; D004261:DNA Replication; D004268:DNA-Binding Proteins; D003609:Dactinomycin / Q000494:pharmacology; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D004789:Enzyme Activation; D006801:Humans; D046911:Macromolecular Substances; D008845:Microinjections; D017232:Oncogene Proteins v-mos / Q000378:metabolism; D009865:Oocytes / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012313:RNA / Q000096:biosynthesis; D056465:Retinoblastoma-Binding Protein 1; D016196:S Phase / Q000235:genetics; D050680:Transcription Factor DP1; D014157:Transcription Factors / Q000378:metabolism*; D014981:Xenopus; D029867:Xenopus Proteins
chemical_list: D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D019927:Cyclin E; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; D046911:Macromolecular Substances; D017232:Oncogene Proteins v-mos; D011500:Protein Synthesis Inhibitors; D056465:Retinoblastoma-Binding Protein 1; C493737:TFDP1 protein, Xenopus; D050680:Transcription Factor DP1; D014157:Transcription Factors; D029867:Xenopus Proteins; D003609:Dactinomycin; D012313:RNA; D017346:Protein Serine-Threonine Kinases; D042846:CDC2-CDC28 Kinases; C495894:CDK2 protein, human; C495891:Cdk2 protein, Xenopus; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases