TY - JOUR
T1 - Regulation of the Drosophila transcription factor, Cubitus interruptus, by two conserved domains
AU - Croker, Jennifer A.
AU - Ziegenhorn, Suzanne L.
AU - Holmgren, Robert A.
N1 - Funding Information:
We are grateful for antibodies provided by Nipam Patel (Anti-En) and Isabel Guerrero (Anti-Ptc). We thank K. Bochenska for generating the data for Fig. 9 , R. Clubb for helping to build the ΔNR construct, M. Yoshida for generously providing LMB, S. Smolik for generating the ci-GAL4 transgenic line, K. Kantor and K. McCabe for generating other transgenic lines, V. Wu for providing varicose/pACT.2/YD119, B. Sisson for providing UAS-Su(fu), and W. Russin for assistance with confocal microscopy. We also thank M. Lefers, B. Sisson, K. McCabe, and M. Dempsey for discussions and critical comments on the manuscript. This work is supported by NIH grants GM57450 and ES10549, the Robert H. Lurie Comprehensive Cancer Center, the Cell and Molecular Basis of Disease Training Grant, and the Training Program in Oncogenesis and Developmental Biology.
PY - 2006/3/15
Y1 - 2006/3/15
N2 - Hedgehog signaling is required for the development of many organisms, including Drosophila. In flies, Hh patterns the embryonic epidermis and larval imaginal discs by regulating the transcription factor, Cubitus interruptus (Ci). To date, three levels of regulation have been identified: proteolytic processing into a repressor, nuclear import, and activation. In this report, we characterize the function of two Ci domains that are conserved in the vertebrate homologues, GLI1, GLI2, and GLI3. One domain includes the first two of five C2-H2 zinc-fingers. While conserved in all members of the GLI/Ci family, the first two fingers do not appear to make significant contacts with the DNA target sequence. Ci protein lacking this region is still able to interact with the cytoplasmic complex and activate transcription in embryos and wing imaginal discs, but it is no longer processed into the repressor form. The second domain, termed NR for "N-terminal Regulatory", binds Suppressor of Fused. Deletion of this region has little effect on embryonic patterning, but compromises cytoplasmic retention of Ci. Analysis of the amino acid sequence of this domain identifies 11 perfectly conserved serines and one tyrosine. We propose that this region may be modified, possibly by phosphorylation, to regulate Ci nuclear import.
AB - Hedgehog signaling is required for the development of many organisms, including Drosophila. In flies, Hh patterns the embryonic epidermis and larval imaginal discs by regulating the transcription factor, Cubitus interruptus (Ci). To date, three levels of regulation have been identified: proteolytic processing into a repressor, nuclear import, and activation. In this report, we characterize the function of two Ci domains that are conserved in the vertebrate homologues, GLI1, GLI2, and GLI3. One domain includes the first two of five C2-H2 zinc-fingers. While conserved in all members of the GLI/Ci family, the first two fingers do not appear to make significant contacts with the DNA target sequence. Ci protein lacking this region is still able to interact with the cytoplasmic complex and activate transcription in embryos and wing imaginal discs, but it is no longer processed into the repressor form. The second domain, termed NR for "N-terminal Regulatory", binds Suppressor of Fused. Deletion of this region has little effect on embryonic patterning, but compromises cytoplasmic retention of Ci. Analysis of the amino acid sequence of this domain identifies 11 perfectly conserved serines and one tyrosine. We propose that this region may be modified, possibly by phosphorylation, to regulate Ci nuclear import.
KW - Cubitus interruptus
KW - Drosophila
KW - Hedgehog
KW - Signal transduction
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U2 - 10.1016/j.ydbio.2005.12.020
DO - 10.1016/j.ydbio.2005.12.020
M3 - Article
C2 - 16413529
AN - SCOPUS:33645006077
SN - 0012-1606
VL - 291
SP - 368
EP - 381
JO - Developmental Biology
JF - Developmental Biology
IS - 2
ER -