Hedgehog signaling plays conserved roles in controlling embryonic development; its dysregulation has been implicated in many human diseases including cancers. Hedgehog signaling has an unusual reception system consisting of two transmembrane proteins, Patched receptor and Smoothened signal transducer. Although activation of Smoothened and its downstream signal transduction have been intensively studied, less is known about how Patched receptor is regulated, and particularly how this regulation contributes to appropriate Hedgehog signal transduction. Here we identified a novel role of Smurf E3 ligase in regulating Hedgehog signaling by controlling Patched ubiquitination and turnover. Moreover, we showed that Smurf-mediated Patched ubiquitination depends on Smo activity in wing discs. Mechanistically, we found that Smo interacts with Smurf and promotes it to mediate Patched ubiquitination by targeting the K1261 site in Ptc. The further mathematic modeling analysis reveals that a bidirectional control of activation of Smo involving Smurf and Patched is important for signal-receiving cells to precisely interpret external signals, thereby maintaining Hedgehog signaling reliability. Finally, our data revealed an evolutionarily conserved role of Smurf proteins in controlling Hh signaling by targeting Ptc during development.
Pubmed ID: 24302888 RIS Download
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Biomaterial supply resource which collects, maintains, and distributes independent transgenic fly lines. Most of the 38,000 fly lines are RNAi lines, but VDRC also maintains a collection of enhancer-GAL4 driver lines. Nearly all lines are in duplicate. Users can search for the stocks or DNA constructs for the gene of interest by entering CG number, synonym, or Transformant ID.
View all literature mentionsDrosophila melanogaster with name w[1118]; P{w[+mC]=UAS-EGFP}5a.2 from BDSC.
View all literature mentionsThis monoclonal targets Patched (extracellular region)
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