RRC ID 28904
著者 Zhang Z, Feng J, Pan C, Lv X, Wu W, Zhou Z, Liu F, Zhang L, Zhao Y.
タイトル Atrophin-Rpd3 complex represses Hedgehog signaling by acting as a corepressor of CiR.
ジャーナル J Cell Biol
Abstract The evolutionarily conserved Hedgehog (Hh) signaling pathway is transduced by the Cubitus interruptus (Ci)/Gli family of transcription factors that exist in two distinct repressor (Ci(R)/Gli(R)) and activator (Ci(A)/Gli(A)) forms. Aberrant activation of Hh signaling is associated with various human cancers, but the mechanism through which Ci(R)/Gli(R) properly represses target gene expression is poorly understood. Here, we used Drosophila melanogaster and zebrafish models to define a repressor function of Atrophin (Atro) in Hh signaling. Atro directly bound to Ci through its C terminus. The N terminus of Atro interacted with a histone deacetylase, Rpd3, to recruit it to a Ci-binding site at the decapentaplegic (dpp) locus and reduce dpp transcription through histone acetylation regulation. The repressor function of Atro in Hh signaling was dependent on Ci. Furthermore, Rerea, a homologue of Atro in zebrafish, repressed the expression of Hh-responsive genes. We propose that the Atro-Rpd3 complex plays a conserved role to function as a Ci(R) corepressor.
巻・号 203(4)
ページ 575-83
公開日 2013-11-25
DOI 10.1083/jcb.201306012
PII jcb.201306012
PMID 24385484
PMC PMC3840934
MeSH Acetylation Animals Binding Sites Co-Repressor Proteins / metabolism DNA-Binding Proteins / metabolism* Drosophila Proteins / metabolism* Drosophila melanogaster / metabolism Evolution, Molecular Genetic Loci / genetics Hedgehog Proteins / metabolism* Histone Deacetylase 1 / metabolism* Histones / metabolism Humans Intracellular Signaling Peptides and Proteins Protein Binding Signal Transduction* Transcription Factors / metabolism* Zebrafish / metabolism Zebrafish Proteins / metabolism*
IF 8.811
引用数 19
WOS 分野 CELL BIOLOGY
リソース情報
ショウジョウバエ 2125R-1