title: XGef influences XRINGO/CDK1 signaling and CPEB activation during Xenopus oocyte maturation.
abstract: CPEB-mediated polyadenylation-induced translation of several developmentally important mRNAs drives Xenopus laevis oocyte meiotic progression and production of fertilizable eggs. To date, the signal transduction events that induce CPEB activation remain somewhat unclear, however, XGef has been shown to be involved in this process. P42 MAPK (ERK2) activity and XRINGO accumulation are also required for the activating phosphorylation of CPEB. We show here that XGef activity influences the early meiotic function of XRINGO/CDK1, a novel component of the progesterone signaling pathway. An XGef-specific antibody depresses XRINGO-induced GVBD, whereas XGef overexpression accelerates this process. XGef and CPEB interact with XRINGO in immature and maturing oocyte extracts and XGef, XRINGO and ERK2 interact directly in vitro. These data suggest that an XGef/XRINGO/ERK2/CPEB complex forms in ovo during early meiotic resumption. Notably, specific inhibition of XRINGO/CDK1 activity in CPEB phosphorylation-competent extracts completely blocks phosphorylation of CPEB, which suggests that XRINGO/CDK1 directly phosphorylates CPEB. Finally, overexpression of XGef (65-360), which cannot bind CPEB or ERK2, but is capable of XRINGO association, blocks XRINGO-induced meiotic progression potentially through titration of endogenous XRINGO. Combined, our results suggest that XGef is involved in XRINGO/CDK1 mediated activation of CPEB and that an XGef/XRINGO/ERK2/CPEB complex forms in ovo to facilitate this process.
authors.affiliation: Biology Department, Boston College, 140 Commonwealth Avenue, Chestnut Hill, MA 02467, USA.
authors.forename: Peiwen
authors.initials: P
authors.lastname: Kuo
authors.forename: Erika
authors.initials: E
authors.lastname: Runge
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Lu
authors.forename: Laura E
authors.initials: LE
authors.lastname: Hake
mesh_terms: D000818:Animals; D016203:CDC2 Protein Kinase / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000378:metabolism*; D008540:Meiosis / Q000235:genetics; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics; D009865:Oocytes / Q000254:growth & development* / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism*; D014982:Xenopus laevis / Q000196:embryology* / Q000235:genetics / Q000378:metabolism; D039221:mRNA Cleavage and Polyadenylation Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: C502823:ARHGEF39 protein, Xenopus; D018797:Cell Cycle Proteins; C490388:Cpeb1 protein, Xenopus; D020662:Guanine Nucleotide Exchange Factors; D014157:Transcription Factors; D029867:Xenopus Proteins; C119055:ls27 protein, Xenopus; D039221:mRNA Cleavage and Polyadenylation Factors; D016203:CDC2 Protein Kinase; D019950:Mitogen-Activated Protein Kinase 1