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dc.contributor.authorSarkissian, Madathia
dc.contributor.authorMendez, Raul
dc.contributor.authorRichter, Joel D.
dc.date2022-08-11T08:08:47.000
dc.date.accessioned2022-08-23T16:08:41Z
dc.date.available2022-08-23T16:08:41Z
dc.date.issued2004-01-16
dc.date.submitted2008-12-09
dc.identifier.citationGenes Dev. 2004 Jan 1;18(1):48-61. <a href="http://dx.doi.org/10.1101/gad.1136004">Link to article on publisher's site</a>
dc.identifier.issn0890-9369 (Print)
dc.identifier.doi10.1101/gad.1136004
dc.identifier.pmid14724178
dc.identifier.urihttp://hdl.handle.net/20.500.14038/32507
dc.description.abstractProgesterone stimulation of Xenopus oocyte maturation requires the cytoplasmic polyadenylation-induced translation of mos and cyclin B mRNAs. One cis element that drives polyadenylation is the CPE, which is bound by the protein CPEB. Polyadenylation is stimulated by Aurora A (Eg2)-catalyzed CPEB serine 174 phosphorylation, which occurs soon after oocytes are exposed to progesterone. Here, we show that insulin also stimulates Aurora A-catalyzed CPEB S174 phosphorylation, cytoplasmic polyadenylation, translation, and oocyte maturation. However, these insulin-induced events are uniquely controlled by PI3 kinase and PKC-zeta, which act upstream of Aurora A. The intersection of the progesterone and insulin signaling pathways occurs at glycogen synthase kinase 3 (GSK-3), which regulates the activity of Aurora A. GSK-3 and Aurora A interact in vivo, and overexpressed GSK-3 inhibits Aurora A-catalyzed CPEB phosphorylation. In vitro, GSK-3 phosphorylates Aurora A on S290/291, the result of which is an autophosphorylation of serine 349. GSK-3 phosphorylated Aurora A, or Aurora A proteins with S290/291D or S349D mutations, have reduced or no capacity to phosphorylate CPEB. Conversely, Aurora A proteins with S290/291A or S349A mutations are constitutively active. These results suggest that the progesterone and insulin stimulate maturation by inhibiting GSK-3, which allows Aurora A activation and CPEB-mediated translation.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=14724178&dopt=Abstract">Link to Article in PubMed</a>
dc.relation.urlhttp://dx.doi.org/10.1101/gad.1136004
dc.subjectAmino Acid Sequence; Animals; Cell Cycle Proteins; Female; Glycogen Synthase Kinase 3; Gonadotropins, Equine; Insulin; Molecular Sequence Data; Mutagenesis, Site-Directed; Oocytes; Peptide Fragments; Phosphorylation; Poly A; Progesterone; Protein Kinases; Protein-Serine-Threonine Kinases; Transcription Factors; Xenopus Proteins; Xenopus laevis; mRNA Cleavage and Polyadenylation Factors
dc.subjectLife Sciences
dc.subjectMedicine and Health Sciences
dc.titleProgesterone and insulin stimulation of CPEB-dependent polyadenylation is regulated by Aurora A and glycogen synthase kinase-3
dc.typeJournal Article
dc.source.journaltitleGenes and development
dc.source.volume18
dc.source.issue1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/gsbs_sp/1074
dc.identifier.contextkey678841
html.description.abstract<p>Progesterone stimulation of Xenopus oocyte maturation requires the cytoplasmic polyadenylation-induced translation of mos and cyclin B mRNAs. One cis element that drives polyadenylation is the CPE, which is bound by the protein CPEB. Polyadenylation is stimulated by Aurora A (Eg2)-catalyzed CPEB serine 174 phosphorylation, which occurs soon after oocytes are exposed to progesterone. Here, we show that insulin also stimulates Aurora A-catalyzed CPEB S174 phosphorylation, cytoplasmic polyadenylation, translation, and oocyte maturation. However, these insulin-induced events are uniquely controlled by PI3 kinase and PKC-zeta, which act upstream of Aurora A. The intersection of the progesterone and insulin signaling pathways occurs at glycogen synthase kinase 3 (GSK-3), which regulates the activity of Aurora A. GSK-3 and Aurora A interact in vivo, and overexpressed GSK-3 inhibits Aurora A-catalyzed CPEB phosphorylation. In vitro, GSK-3 phosphorylates Aurora A on S290/291, the result of which is an autophosphorylation of serine 349. GSK-3 phosphorylated Aurora A, or Aurora A proteins with S290/291D or S349D mutations, have reduced or no capacity to phosphorylate CPEB. Conversely, Aurora A proteins with S290/291A or S349A mutations are constitutively active. These results suggest that the progesterone and insulin stimulate maturation by inhibiting GSK-3, which allows Aurora A activation and CPEB-mediated translation.</p>
dc.identifier.submissionpathgsbs_sp/1074
dc.contributor.departmentProgram in Molecular Medicine
dc.contributor.departmentGraduate School of Biomedical Sciences
dc.source.pages48-61


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