PHYL acts to down-regulate TTK88, a transcriptional repressor of neuronal cell fates, by a SINA-dependent mechanism.
We show that Tramtrack (TTK88) expression represses neuronal fate determination in the developing Drosophila eye. Phyllopod (PHYL) acts to antagonize this repression by a mechanism that requires Seven In Absentia (SINA) and is associated with decreased TTK88 protein levels, but not reduced ttk88 gene transcription or mRNA stability. We present evidence that SINA, PHYL, and TTK88 physically interact and that SINA interacts genetically and physically with UBCD1, a component of the ubiquitin-dependent protein degradation pathway. Our results suggest a model in which activation of the Sevenless receptor tyrosine kinase induces PHYL expression, which then acts with SINA to target the transcriptional repressor TTK88 for degradation, thereby promoting R7 cell fate specification.
Tang
A H
AH
Howard Hughes Medical Institute, Department of Molecular and Cell Biology, University of California, Berkeley 94720-3200, USA.
Neufeld
T P
TP
Kwan
E
E
Rubin
G M
GM
D017398:Alternative Splicing; D000818:Animals; D002460:Cell Line; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000378:metabolism; D004330:Drosophila / Q000196:embryology / Q000235:genetics; D029721:Drosophila Proteins; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000502:physiology; D005123:Eye / Q000166:cytology / Q000196:embryology / Q000648:ultrastructure; D018507:Gene Expression Regulation, Developmental; D005838:Genotype; D008025:Ligases / Q000378:metabolism; D008855:Microscopy, Electron, Scanning; D009474:Neurons / Q000166:cytology* / Q000502:physiology*; D009687:Nuclear Proteins / Q000096:biosynthesis* / Q000378:metabolism*; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011485:Protein Binding; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000378:metabolism; D012097:Repressor Proteins; D014157:Transcription Factors / Q000096:biosynthesis; D014158:Transcription, Genetic; D014162:Transfection; D044763:Ubiquitin-Conjugating Enzymes; D044767:Ubiquitin-Protein Ligases; D000098563:Seven in Absentia Proteins
D017931:DNA Primers; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; D011994:Recombinant Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; C092070:phyl protein, Drosophila; C075878:ttk protein, Drosophila; D044763:Ubiquitin-Conjugating Enzymes; D044767:Ubiquitin-Protein Ligases; D000098563:Seven in Absentia Proteins; D008025:Ligases