西亚试剂：Atrophin–Rpd3 complex represses Hedgehog signaling by actin

发布时间：2025-12-13

Atrophin–Rpd3 complex represses Hedgehog signaling by acting as a corepressor of CiR

Zhao Zhang1， Jing Feng1， Chenyu Pan1， Xiangdong Lv1， Wenqing Wu1， Zhaocai Zhou1， Feng Liu2， Lei Zhang1， and Yun Zhao1

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.

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