Nuclear trafficking of Cubitus interruptus in the transcriptional regulation of Hedgehog target gene expression.
Transcriptional activation of Hedgehog (Hh) target genes requires Cubitus interruptus, a 155 kDa cytoplasmic zinc finger protein (Ci155), which in the absence of Hh signaling is processed to form a nuclear repressor (Ci75). We show that Hh signaling reduces phosphorylation of Ci155, and this reduction in turn appears to decrease processing. Blocking processing with proteasome inhibitors or altered Ci proteins, however, is insufficient for activation of Hh targets. We find that Hh signaling increases the rate of Ci155 nuclear import, resulting in significant nuclear accumulation. Even in the absence of signaling, nuclear accumulation of Ci155 suffices for significant induction of Hh targets, and active nuclear export of Ci155 is an essential mechanism for maintenance of the unstimulated state.
Chen
C H
CH
Howard Hughes Medical Institute, Department of Molecular Biology and Genetics, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
von Kessler
D P
DP
Park
W
W
Wang
B
B
Ma
Y
Y
Beachy
P A
PA
D000818:Animals; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D004330:Drosophila / Q000235:genetics*; D029721:Drosophila Proteins; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D053823:Hedgehog Proteins; D019476:Insect Proteins / Q000235:genetics* / Q000378:metabolism; D007700:Kinetics; D016133:Polymerase Chain Reaction; D011994:Recombinant Proteins / Q000378:metabolism; D015183:Restriction Mapping; D015398:Signal Transduction; D014157:Transcription Factors; D014158:Transcription, Genetic; D014162:Transfection; D016335:Zinc Fingers
D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D053823:Hedgehog Proteins; D019476:Insect Proteins; D011994:Recombinant Proteins; D014157:Transcription Factors; C092937:ci protein, Drosophila; C077245:hh protein, Drosophila