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ZFIN ID: ZDB-PUB-140303-20
Atrophin-Rpd3 complex represses Hedgehog signaling by acting as a corepressor of CiR
Zhang, Z., Feng, J., Pan, C., Lv, X., Wu, W., Zhou, Z., Liu, F., Zhang, L., and Zhao, Y.
Date: 2013
Source: The Journal of cell biology   203(4): 575-583 (Journal)
Registered Authors: Liu, Feng
Keywords: none
MeSH Terms:
  • 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
  • Protein Binding
  • Signal Transduction*
  • Transcription Factors/metabolism*
  • Zebrafish/metabolism
  • Zebrafish Proteins/metabolism*
PubMed: 24385484 Full text @ J. Cell Biol.

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 (CiR/GliR) and activator (CiA/GliA) forms. Aberrant activation of Hh signaling is associated with various human cancers, but the mechanism through which CiR/GliR 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 CiR corepressor.