Geminin and Brahma act antagonistically to regulate EGFR-Ras-MAPK signaling in Drosophila

Anabel Herr, Lisa Mckenzie, Randy Suryadinata, Martin Sadowski, Linda M Parsons, Boris Sarcevic, Helena Richardson

Research output: Contribution to journalArticleResearchpeer-review

12 Citations (Scopus)

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 (Brill) 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 Brill 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.
Original languageEnglish
Pages (from-to)36 - 51
Number of pages16
JournalDevelopmental Biology
Volume344
Issue number1
DOIs
Publication statusPublished - 2010
Externally publishedYes

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