Journal article

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 E Richardson



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 m..

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University of Melbourne Researchers


Funding Acknowledgements

We are grateful to Nick Dyson, Leonie Quinn, Tony Brumby, Michelle Longworth, Erica Sloan and Deborah Roczo for their advice during the course of this study and on the earlier versions of this manuscript, and to the three unknown reviewers for their insight and helpful comments. We particularly appreciate Nick Dyson's support in allowing some of the experiments in this study to be completed in his laboratory We thank Peter Burke and Michelle Coombe for their technical help with the generation of transgenic flies. We thank Christian Muchardt for generously providing the Brm and Snr1 antibodies, John Tamkun for the UAS-brm<SUP>K804R</SUP> flies, Richard Carthew for the pWIZ vector, Laura Johnston for the en-GAL4, UAS-GFP and C96-GAL4 flies, Jessica Treisman for the UAS-Osa flies, Andrew Dingwall for the UAS-Snr1 and UAS-Snr1 cdel.3 flies, the Bloomington Center for providing other fly stocks and the Developmental Studies Hybridoma Banks (DSHB) at the University of Iowa for antibodies. We also acknowledge the importance of the Flybase database for this study This study was supported by grants from the Australian Research Council to H.E.R., to B.S. and HER., and by the Peter MacCallum Cancer Center Special Purpose Funds H.E.R. was supported by Welcome and NHMRC Senior Research Fellowships.