EGFR signaling attenuates Groucho-dependent repression to antagonize Notch transcriptional output.
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 Given that there are genetic interactions between gro and components of the EGFR pathway (ref. 9 and P.H. et al., unpublished results), we tested whether Gro is at a crossroad between this and other pathways.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.
Hasson
Peleg
P
Department of Biochemistry, Faculty of Medicine, The Hebrew University, PO Box 12272, Jerusalem 91120, Israel.
Egoz
Nirit
N
Winkler
Clint
C
Volohonsky
Gloria
G
Jia
Songtao
S
Dinur
Tama
T
Volk
Talila
T
Courey
Albert J
AJ
Paroush
Ze'ev
Z
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins / Q000378:metabolism*; D029721:Drosophila Proteins / Q000378:metabolism; D004331:Drosophila melanogaster / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology*; D007150:Immunohistochemistry; D008565:Membrane Proteins / Q000378:metabolism*; D051880:Receptors, Notch; D012097:Repressor Proteins / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D014921:Wings, Animal / Q000002:abnormalities / Q000254:growth & development; D018631:ras Proteins / Q000378:metabolism
D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D066246:ErbB Receptors; D008565:Membrane Proteins; D051880:Receptors, Notch; D012097:Repressor Proteins; D018631:ras Proteins; C497759:N protein, Drosophila; C091023:gro protein, Drosophila; C417283:Ras85D protein, Drosophila