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

Herr, Anabel, Mckenzie, Lisa, Suryadinata, Randy, Sadowski, Martin, Parsons, Linda M., Sarcevic, Boris, & Richardson, Helena E. (2010) Geminin and Brahma act antagonistically to regulate EGFR–Ras–MAPK signaling in Drosophila. Developmental Biology, 344(1), pp. 36-51.

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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.

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ID Code: 74830
Item Type: Journal Article
Refereed: Yes
DOI: 10.1016/j.ydbio.2010.04.006
ISSN: 0012-1606
Divisions: Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: Copyright 2010 Elsevier
Copyright Statement: This is the author’s version of a work that was accepted for publication in Developmental Biology. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Developmental Biology, [VOL 344, ISSUE 1, (2010)] DOI: 10.1016/j.ydbio.2010.04.006
Deposited On: 08 Aug 2014 00:15
Last Modified: 11 Aug 2014 03:01

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