Groucho-dependent and -independent repression activities of Runt domain proteins.
Runt domain proteins are transcriptional regulators that specify cell fates for processes extending from pattern formation in insects to leukemogenesis in humans. Runt domain family members are defined based on the presence of the 128-amino-acid Runt domain, which is necessary and sufficient for sequence-specific DNA binding. We demonstrate an evolutionarily conserved protein-protein interaction between Runt domain proteins and the corepressor Groucho. The interaction, however, is independent of the Runt domain and can be mapped to a 5-amino-acid sequence, VWRPY, present at the C terminus of all Runt domain proteins. Drosophila melanogaster Runt and Groucho interact genetically; the in vivo repression of a subset of Runt-regulated genes is dependent on the interaction with Groucho and is sensitive to Groucho dosage. Runt's repression of one gene, engrailed, is independent of VWRPY and Groucho, thus demonstrating alternative mechanisms for repression by Runt domain proteins. Unlike other transcriptional regulatory proteins that interact with Groucho, Runt domain proteins are known to activate transcription. This suggests that the Runt domain protein-Groucho interaction may be regulated.
Aronson
B D
BD
Department of Biochemistry and Cell Biology, Institute for Cell and Developmental Biology, State University of New York at Stony Brook, 11794-5215, USA.
Fisher
A L
AL
Blechman
K
K
Caudy
M
M
Gergen
J P
JP
D000595:Amino Acid Sequence; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D002478:Cells, Cultured; D017124:Conserved Sequence; D004268:DNA-Binding Proteins / Q000378:metabolism*; D029721:Drosophila Proteins; D004331:Drosophila melanogaster; D008969:Molecular Sequence Data; D009687:Nuclear Proteins; D012097:Repressor Proteins / Q000378:metabolism*; D017384:Sequence Deletion; D014157:Transcription Factors; D014158:Transcription, Genetic
D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D009687:Nuclear Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; C091023:gro protein, Drosophila; C080833:run protein, Drosophila