PMID- 10458606 OWN - NLM STAT- MEDLINE DCOM- 19990909 LR - 20190705 IS - 0092-8674 (Print) IS - 0092-8674 (Linking) VI - 98 IP - 3 DP - 1999 Aug 6 TI - Nuclear trafficking of Cubitus interruptus in the transcriptional regulation of Hedgehog target gene expression. PG - 305-16 AB - 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. FAU - Chen, C H AU - Chen CH AD - Howard Hughes Medical Institute, Department of Molecular Biology and Genetics, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA. FAU - von Kessler, D P AU - von Kessler DP FAU - Park, W AU - Park W FAU - Wang, B AU - Wang B FAU - Ma, Y AU - Ma Y FAU - Beachy, P A AU - Beachy PA LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Cell JT - Cell JID - 0413066 RN - 0 (DNA-Binding Proteins) RN - 0 (Drosophila Proteins) RN - 0 (Hedgehog Proteins) RN - 0 (Insect Proteins) RN - 0 (Recombinant Proteins) RN - 0 (Transcription Factors) RN - 0 (ci protein, Drosophila) RN - 149291-21-4 (hh protein, Drosophila) SB - IM MH - Animals MH - Cell Line MH - Cell Nucleus/*metabolism MH - DNA-Binding Proteins/*genetics/*metabolism MH - Drosophila/*genetics MH - *Drosophila Proteins MH - *Gene Expression Regulation MH - Genes, Reporter MH - Hedgehog Proteins MH - Insect Proteins/*genetics/metabolism MH - Kinetics MH - Polymerase Chain Reaction MH - Recombinant Proteins/metabolism MH - Restriction Mapping MH - Signal Transduction MH - Transcription Factors MH - *Transcription, Genetic MH - Transfection MH - Zinc Fingers EDAT- 1999/08/24 00:00 MHDA- 1999/08/24 00:01 CRDT- 1999/08/24 00:00 PHST- 1999/08/24 00:00 [pubmed] PHST- 1999/08/24 00:01 [medline] PHST- 1999/08/24 00:00 [entrez] AID - S0092-8674(00)81960-1 [pii] AID - 10.1016/s0092-8674(00)81960-1 [doi] PST - ppublish SO - Cell. 1999 Aug 6;98(3):305-16. doi: 10.1016/s0092-8674(00)81960-1.