Abstract
Crosstalk between signaling pathways is crucial for the generation of complex and varied transcriptional networks. Antagonism between the EGF-receptor (EGFR) and Notch pathways in particular is well documented, although the underlying mechanism is poorly understood. The global corepressor Groucho (Gro) and its transducin-like Enhancer-of-split (TLE) mammalian homologs mediate repression by a myriad of repressors, including effectors of the Notch, Wnt (Wg) and TGF-β (Dpp) signaling cascades1-8. Given that there are genetic interactions between gro and components of the EGFR pathway9 (ref. 9 and P.H. et al., unpublished results), we tested whether Gro is at a crossroad between this and other pathways. Here we show that phosphorylation of Gro in response to MARK activation weakens its repressor capacity, attenuating Gro-dependent transcriptional silencing by the Enhancer-of-split proteins, effectors of the Notch cascade. Thus, Gro is a new junction between signaling pathways, enabling EGFR signaling to antagonize transcriptional output by Notch and potentially other Gro-dependent pathways.
| Original language | English |
|---|---|
| Pages (from-to) | 101-105 |
| Number of pages | 5 |
| Journal | Nature Genetics |
| Volume | 37 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 2005 |
Bibliographical note
Funding Information:We thank K. Basler, H. Bellen, S. Bray, S. Cohen, C. Delidakis, O. Gerlitz, E. Hafen, Y. Hiromi, F. Laski, E. Martin-Blanco, J. Modolell, D. Montell, G. Morata, A. Salzberg, T. Schupbach, B. Shilo, G. Struhl, the Bloomington Stock Centre and the Developmental Studies Hybridoma Bank for fly stocks, reagents and antibodies; S. Katzav, C. Levy and R. Grossman for technical assistance; and Y. Bergman, D. Ish-Horowicz, G. Jiménez, B. Shilo and J. Yisraeli for comments on the manuscript. This work was supported by grants from the Israel Science Foundation, Israel Cancer Research Fund, Lejwa Fund for Biochemistry and the Król Charitable Foundation to Z.P., and by a grant from the US National Institutes of Health to A.J.C. P.H. acknowledges a Clore Foundation PhD Scholarship, and C.W. acknowledges a USPHS National Research Service Training Award. Z.P. is a Braun Lecturer.