An EGFR/Ebi/Sno pathway promotes delta expression by inactivating Su(H)/SMRTER repression during inductive notch signaling.
The Notch and Epidermal Growth Factor Receptor (EGFR) pathways both regulate proliferation and differentiation, and the cellular response to each is often influenced by the other. Here, we describe a mechanism that links them in a sequential fashion, in the developing compound eye of Drosophila. EGFR activation induces photoreceptor (R cell) differentiation and promotes their expression of Delta. This Notch ligand then induces neighboring cells to become nonneuronal cone cells. ebi and strawberry notch (sno) regulate EGFR-dependent Delta transcription by antagonizing a repressor function of Suppressor of Hairless (Su(H)). Sno binds to Su(H), and Ebi, an F-box/WD40 protein, forms a complex with Su(H) and the corepressor SMRTER. EGFR-activated transcriptional derepression requires ebi and sno, is proteasome-dependent, and correlates with the translocation of SMRTER to the cytoplasm.
Tsuda
Leo
L
Department of Biological Chemistry and Department of Human Genetics, Molecular Biology Institute, Los Angeles, CA 90095, USA.
Nagaraj
Raghavendra
R
Zipursky
S Lawrence
SL
Banerjee
Utpal
U
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004330:Drosophila; D029721:Drosophila Proteins / Q000378:metabolism*; D066246:ErbB Receptors; D019204:GTP-Binding Proteins; D019476:Insect Proteins / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D017956:Photoreceptor Cells, Invertebrate; D051880:Receptors, Notch; D012097:Repressor Proteins / Q000378:metabolism*; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism*
D051792:Basic Helix-Loop-Helix Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D066246:ErbB Receptors; D019204:GTP-Binding Proteins; D019476:Insect Proteins; D008565:Membrane Proteins; D009687:Nuclear Proteins; D051880:Receptors, Notch; D012097:Repressor Proteins; D014157:Transcription Factors; C084530:E(spl)mdelta-HLH protein, Drosophila; C497759:N protein, Drosophila; C088731:Su(H) protein, Drosophila; C119014:ebi protein, Drosophila; C106204:sno protein, Drosophila