Drosophila CtBP: a Hairy-interacting protein required for embryonic segmentation and hairy-mediated transcriptional repression.
hairy is a Drosophila pair-rule segmentation gene that functions genetically as a repressor. To isolate protein components of Hairy-mediated repression, we used a yeast interaction screen and identified a Hairy-interacting protein, the Drosophila homolog of the human C-terminal-binding protein (CtBP). Human CtBP is a cellular phosphoprotein that interacts with the C-terminus of the adenovirus E1a oncoprotein and functions as a tumor suppressor. dCtBP also interacts with E1a in a directed yeast two-hybrid assay. We show that dCtBP interacts specifically and directly with a small, previously uncharacterized C-terminal region of Hairy. dCtBP activity appears to be specific to Hairy of the Hairy/Enhancer of split [E(spl)]/Dpn basic helix-loop-helix protein class. We identified a P-element insertion within the dCtBP transcription unit that fails to complement alleles of a known locus, l(3)87De. We demonstrate that dCtBP is essential for proper embryonic segmentation by analyzing embryos lacking maternal dCtBP activity. While Hairy is probably not the only segmentation gene interacting with dCtBP, we show dose-sensitive genetic interactions between dCtBP and hairy mutations.
Poortinga
G
G
Division of Basic Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, Seattle, WA 98109, USA.
Watanabe
M
M
Parkhurst
S M
SM
D017500:Adenovirus E1A Proteins / Q000378:metabolism; D000429:Alcohol Oxidoreductases; D000595:Amino Acid Sequence; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D004330:Drosophila / Q000196:embryology* / Q000235:genetics; D029721:Drosophila Proteins; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D017344:Genes, Insect / Q000235:genetics; D005804:Genes, Lethal / Q000235:genetics; D005816:Genetic Complementation Test; D006801:Humans; D019476:Insect Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D012333:RNA, Messenger / Q000032:analysis; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D015183:Restriction Mapping; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D014158:Transcription, Genetic / Q000502:physiology
D017500:Adenovirus E1A Proteins; D000429:Alcohol Oxidoreductases; D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D019476:Insect Proteins; D010750:Phosphoproteins; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; C489235:hairy protein, Drosophila; C061841:hairy protein, insect; C096794:C-terminal binding protein