MAE, a dual regulator of the EGFR signaling pathway, is a target of the Ets transcription factors PNT and YAN.
Ets transcription factors play crucial roles in regulating diverse cellular processes including cell proliferation, differentiation and survival. Coordinated regulation of the Drosophila Ets transcription factors YAN and POINTED is required for eliciting appropriate responses to Receptor Tyrosine Kinase (RTK) signaling. YAN, a transcriptional repressor, and POINTED, a transcriptional activator, compete for regulatory regions of common target genes, with the ultimate outcome likely influenced by context-specific interactions with binding partners such as MAE. Previous work in cultured cells has led us to propose that MAE attenuates the transcriptional activity of both YAN and POINTED, although its effects on POINTED remain controversial. Here we describe a new layer of complexity to this regulatory hierarchy whereby mae expression is itself directly regulated by the opposing action of YAN and POINTED. In addition, we report that MAE can antagonize POINTED function during eye development; a finding that suggests MAE operates as a dual positive and negative regulator of RTK-mediated signaling in vivo. Together our results lead us to propose that a combination of protein-protein and transcriptional interactions between MAE, YAN and POINTED establishes a complex regulatory circuit that ensures that both down-regulation and activation of the RTK pathway occur appropriately according to specific developmental context.
Vivekanand
Pavithra
P
Whitehead Institute, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
Tootle
Tina L
TL
Rebay
Ilaria
I
D004268:DNA-Binding Proteins / Q000378:metabolism; D029721:Drosophila Proteins / Q000378:metabolism*; D066246:ErbB Receptors / Q000378:metabolism*; D005123:Eye / Q000196:embryology / Q000378:metabolism; D005124:Eye Abnormalities / Q000235:genetics / Q000378:metabolism; D005136:Eye Proteins / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D018010:Receptors, Invertebrate Peptide / Q000378:metabolism*; D012097:Repressor Proteins / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism
C076188:AOP protein, Drosophila; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D005136:Eye Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D011518:Proto-Oncogene Proteins; D018010:Receptors, Invertebrate Peptide; D012097:Repressor Proteins; D014157:Transcription Factors; C428945:edl protein, Drosophila; C083884:pnt protein, Drosophila; D011494:Protein Kinases; C066532:Egfr protein, Drosophila; D066246:ErbB Receptors