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Originally published as Genetics Published Articles Ahead of Print on July 1, 2007.
Genetics, Vol. 176, 2265-2277, August 2007, Copyright © 2007
doi:10.1534/genetics.107.071225
The Bro1-Domain Protein, EGO-2, Promotes Notch Signaling in Caenorhabditis elegans
Ying Liu and Eleanor M. Maine1
Department of Biology, Syracuse University, Syracuse, New York 13244
1 Corresponding author: Department of Biology, Syracuse University, 108 College Place, Syracuse, NY 13244.
E-mail: emmaine{at}syr.edu
In Caenorhabditis elegans, as in other animals, Notch-type signaling mediates numerous inductive events during development. The mechanism of Notch-type signaling involves proteolytic cleavage of the receptor and subsequent transport of the receptor intracellular domain to the nucleus, where it acts as a transcriptional regulator. Notch-type signaling activity is modulated by post-translational modifications and endocytosis of ligand and receptor. We previously identified the ego-2 (enhancer of glp-1) gene as a positive regulator of germline proliferation that interacts genetically with the GLP-1/Notch signaling pathway in the germline. Here, we show that ego-2 positively regulates signaling in various tissues via both GLP-1 and the second C. elegans Notch-type receptor, LIN-12. ego-2 activity also promotes aspects of development not known to require GLP-1 or LIN-12. The EGO-2 protein contains a Bro1 domain, which is known in other systems to localize to certain endosomal compartments. EGO-2 activity in the soma promotes GLP-1 signaling in the germline, consistent with a role for EGO-2 in production of active ligand. Another C. elegans Bro1-domain protein, ALX-1, is known to interact physically with LIN-12/Notch. We document a complex phenotypic interaction between ego-2 and alx-1, consistent with their relationship being antagonistic with respect to some developmental processes and agonistic with respect to others.
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