Phosphorylation by the DHIPK2 protein kinase modulates the corepressor activity of Groucho.
Groucho function is essential for Drosophila development, acting as a corepressor for specific transcription factors that are downstream targets of various signaling pathways. Here we provide evidence that Groucho is phosphorylated by the DHIPK2 protein kinase. Phosphorylation modulates Groucho corepressor activity by attenuating its protein-protein interaction with a DNA-bound transcription factor. During eye development, DHIPK2 modifies Groucho activity, and eye phenotypes generated by overexpression of Groucho differ depending on its phosphorylation state. Moreover, analysis of nuclear extracts fractionated by column chromatography further shows that phospho-Groucho associates poorly with the corepressor complex, whereas the unphosphorylated form binds tightly. We propose that Groucho phosphorylation by DHIPK2 and its subsequent dissociation from the corepressor complex play a key role in relieving the transcriptional repression of target genes regulated by Groucho, thereby controlling cell fate determination during development.
Choi
Cheol Yong
CY
Laboratory Research program, NHLBI, National Institutes of Health, Bethesda, Maryland 20892, USA. choicy@skku.ac.kr
Kim
Young Ho
YH
Kim
Yong-Ou
YO
Park
Sang Joon
SJ
Kim
Eun-A
EA
Riemenschneider
William
W
Gajewski
Kathleen
K
Schulz
Robert A
RA
Kim
Yongsok
Y
D000595:Amino Acid Sequence; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D001665:Binding Sites; D015153:Blotting, Western; D002352:Carrier Proteins / Q000378:metabolism; D002460:Cell Line; D019070:Cell Lineage; D002845:Chromatography; D002850:Chromatography, Gel; D004247:DNA / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D004330:Drosophila; D029721:Drosophila Proteins / Q000378:metabolism; D005123:Eye / Q000196:embryology*; D005822:Genetic Vectors; D006801:Humans; D007150:Immunohistochemistry; D008156:Luciferases / Q000378:metabolism; D008954:Models, Biological; D008969:Molecular Sequence Data; D009154:Mutation; D010455:Peptides / Q000737:chemistry; D010641:Phenotype; D010766:Phosphorylation; D010957:Plasmids / Q000378:metabolism; D011485:Protein Binding; D011494:Protein Kinases / Q000737:chemistry* / Q000378:metabolism* / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D017434:Protein Structure, Tertiary; D012097:Repressor Proteins / Q000737:chemistry / Q000502:physiology*; D014158:Transcription, Genetic; D014162:Transfection; D019076:Transgenes
D051792:Basic Helix-Loop-Helix Proteins; D002352:Carrier Proteins; D004247:DNA; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D008156:Luciferases; D010455:Peptides; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D012097:Repressor Proteins; C113278:ey protein, Drosophila; C091023:gro protein, Drosophila; C115114:HIPK2 protein, human; C501861:HIPK protein, Drosophila