title: Geminin and Brahma act antagonistically to regulate EGFR-Ras-MAPK signaling in Drosophila.
abstract: Geminin was identified in Xenopus as a dual function protein involved in the regulation of DNA replication and neural differentiation. In Xenopus, Geminin acts to antagonize the Brahma (Brm) chromatin-remodeling protein, Brg1, during neural differentiation. Here, we investigate the interaction of Geminin with the Brm complex during Drosophila development. We demonstrate that Drosophila Geminin (Gem) interacts antagonistically with the Brm-BAP complex during wing development. Moreover, we show in vivo during wing development and biochemically that Brm acts to promote EGFR-Ras-MAPK signaling, as indicated by its effects on pERK levels, while Gem opposes this. Furthermore, gem and brm alleles modulate the wing phenotype of a Raf gain-of-function mutant and the eye phenotype of a EGFR gain-of-function mutant. Western analysis revealed that Gem over-expression in a background compromised for Brm function reduces Mek (MAPKK/Sor) protein levels, consistent with the decrease in ERK activation observed. Taken together, our results show that Gem and Brm act antagonistically to modulate the EGFR-Ras-MAPK signaling pathway, by affecting Mek levels during Drosophila development.
authors.affiliation: Peter MacCallum Cancer Center, Melbourne, Victoria, Australia.
authors.forename: Anabel
authors.initials: A
authors.lastname: Herr
authors.forename: Lisa
authors.initials: L
authors.lastname: Mckenzie
authors.forename: Randy
authors.initials: R
authors.lastname: Suryadinata
authors.forename: Martin
authors.initials: M
authors.lastname: Sadowski
authors.forename: Linda M
authors.initials: LM
authors.lastname: Parsons
authors.forename: Boris
authors.initials: B
authors.lastname: Sarcevic
authors.forename: Helena E
authors.initials: HE
authors.lastname: Richardson
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D018797:Cell Cycle Proteins / Q000378:metabolism*; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000502:physiology*; D066246:ErbB Receptors / Q000378:metabolism*; D064248:Geminin; D018507:Gene Expression Regulation, Developmental; D020935:MAP Kinase Signaling System; D008954:Models, Biological; D009154:Mutation; D010641:Phenotype; D012330:RNA, Double-Stranded / Q000378:metabolism; D015398:Signal Transduction; D015534:Trans-Activators / Q000378:metabolism*; D014921:Wings, Animal; D018631:ras Proteins / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; D029721:Drosophila Proteins; D064248:Geminin; D012330:RNA, Double-Stranded; D015534:Trans-Activators; C086469:brm protein, Drosophila; D066246:ErbB Receptors; D018631:ras Proteins