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-beta (Dpp) signaling cascades. Given that there are genetic interactions between gro and components of the EGFR pathway (ref. 9 and P.H. et al., unpublished results), we tested whether Gro is at a crossroad between this and other pathways.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 MAPK 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.
journal_name
Nat Genetjournal_title
Nature geneticsauthors
Hasson P,Egoz N,Winkler C,Volohonsky G,Jia S,Dinur T,Volk T,Courey AJ,Paroush Zdoi
10.1038/ng1486keywords:
subject
Has Abstractpub_date
2005-01-01 00:00:00pages
101-5issue
1eissn
1061-4036issn
1546-1718pii
ng1486journal_volume
37pub_type
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