RRC ID 38137
Author Oh S, Kato M, Zhang C, Guo Y, Beachy PA.
Title A Comparison of Ci/Gli Activity as Regulated by Sufu in Drosophila and Mammalian Hedgehog Response.
Journal PLoS One
Abstract Suppressor of fused (Su(fu)/Sufu), one of the most conserved components of the Hedgehog (Hh) signaling pathway, binds Ci/Gli transcription factors and impedes activation of target gene expression. In Drosophila, the Su(fu) mutation has a minimal phenotype, and we show here that Ci transcriptional activity in large part is regulated independently of Su(fu) by other pathway components. Mutant mice lacking Sufu in contrast show excessive pathway activity and die as embryos with patterning defects. Here we show that in cultured cells Hh stimulation can augment transcriptional activity of a Gli2 variant lacking Sufu interaction and, surprisingly, that regulation of Hh pathway targets is nearly normal in the neural tube of Sufu-/- mutant embryos that also lack Gli1 function. Some degree of Hh-induced transcriptional activation of Ci/Gli thus can occur independently of Sufu in both flies and mammals. We further note that Sufu loss can also reduce Hh induction of high-threshold neural tube fates, such as floor plate, suggesting a possible positive pathway role for Sufu.
Volume 10(8)
Pages e0135804
Published 2015-1-1
DOI 10.1371/journal.pone.0135804
PII PONE-D-15-11845
PMID 26271100
PMC PMC4536226
MeSH Animals DNA-Binding Proteins / genetics DNA-Binding Proteins / metabolism* Drosophila Drosophila Proteins / genetics Drosophila Proteins / metabolism* Hedgehog Proteins / genetics Hedgehog Proteins / metabolism* Kinesins / genetics Kinesins / metabolism Mice Mice, Mutant Strains Oncogene Proteins / genetics Oncogene Proteins / metabolism* Protein Serine-Threonine Kinases / genetics Protein Serine-Threonine Kinases / metabolism Repressor Proteins / genetics Repressor Proteins / metabolism* Signal Transduction / genetics Signal Transduction / physiology Trans-Activators / genetics Trans-Activators / metabolism* Transcription Factors / genetics Transcription Factors / metabolism* Zinc Finger Protein GLI1
IF 2.74
Times Cited 3
WOS Category CELL BIOLOGY
Resource
Human and Animal Cells C2C12(RCB0987)