Differential regulation of Gli proteins by Sufu in the lung affects PDGF signaling and myofibroblast development.

ABSTRACT: Mammalian Hedgehog (Hh) signaling relies on three Gli transcription factors to mediate Hh responses. This process is controlled in part by a major negative regulator, Sufu, through its effects on Gli protein level, distribution and activity. In this report, we showed that Sufu regulates Gli1 protein levels by antagonizing Numb/Itch. Otherwise, Numb/Itch would induce Gli1 protein degradation. This is in contrast to inhibition of Spop-mediated degradation of Gli2/3 by Sufu. Thus, controlling protein levels of all three Gli genes by Sufu is a conserved mechanism to modulate Hh responses albeit via distinct pathways. These findings in cell-based assays were further validated in vivo. In analyzing how Sufu controls Gli proteins in different tissues, we discovered that loss of Sufu in the lung e

SUBMITTER: Lin C 

PROVIDER: S-EPMC4106470 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature