Atrophin-Rpd3 complex represses Hedgehog signaling by acting as a corepressor of CiR
- Authors
- Zhang, Z., Feng, J., Pan, C., Lv, X., Wu, W., Zhou, Z., Liu, F., Zhang, L., and Zhao, Y.
- ID
- ZDB-PUB-140303-20
- 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.