UbcD1 regulates Hedgehog signaling by directly modulating Ci ubiquitination and processing

Pan, C., Xiong, Y., Lv, X., Xia, Y., Zhang, S., Chen, H., Fan, J., Wu, W., Liu, F., Wu, H., Zhou, Z., Zhang, L., Zhao, Y.
EMBO reports   18: 1922-1934 (Journal)
Registered Authors
Liu, Feng
Drosophila, Ci, Hedgehog, UbcD1, ubiquitination
MeSH Terms
  • Animals
  • Cell Cycle Proteins/genetics
  • Cell Cycle Proteins/metabolism
  • Conserved Sequence
  • DNA-Binding Proteins/genetics
  • DNA-Binding Proteins/metabolism
  • Drosophila Proteins/genetics*
  • Drosophila Proteins/metabolism
  • Drosophila melanogaster/genetics*
  • Drosophila melanogaster/growth & development
  • Drosophila melanogaster/metabolism
  • Embryo, Nonmammalian
  • Gene Expression Regulation, Developmental*
  • Hedgehog Proteins/genetics*
  • Hedgehog Proteins/metabolism
  • Imaginal Discs/growth & development
  • Imaginal Discs/metabolism
  • Larva/genetics
  • Larva/growth & development
  • Larva/metabolism
  • Patched-2 Receptor/genetics
  • Patched-2 Receptor/metabolism
  • Polyubiquitin/genetics
  • Polyubiquitin/metabolism
  • Protein Processing, Post-Translational*
  • Protein Stability
  • Proteolysis
  • Signal Transduction
  • Transcription Factors/genetics
  • Transcription Factors/metabolism
  • Ubiquitin-Conjugating Enzymes/genetics*
  • Ubiquitin-Conjugating Enzymes/metabolism
  • Ubiquitin-Protein Ligases/genetics
  • Ubiquitin-Protein Ligases/metabolism
  • Ubiquitination
  • Zebrafish/genetics*
  • Zebrafish/growth & development
  • Zebrafish/metabolism
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
28887318 Full text @ EMBO Rep.
The Hh pathway controls many morphogenetic processes in metazoans and plays important roles in numerous pathologies and in cancer. Hh signaling is mediated by the activity of the Gli/Ci family of transcription factors. Several studies in Drosophila have shown that ubiquitination by the ubiquitin E3 ligases Slimb and Rdx(Hib) plays a crucial role in controlling Ci stability dependent on the levels of Hh signals. If Hh levels are low, Slimb adds K11- and K48-linked poly-ubiquitin chains on Ci resulting in partial degradation. Ubiquitin E2 enzymes are pivotal in determining the topologies of ubiquitin chains. However, which E2 enzymes participate in the selective ubiquitination-degradation of Ci remains elusive. Here, we find that the E2 enzyme UbcD1 negatively regulates Hh signaling activity in Drosophila wing disks. Genetic and biochemical analyses in wing disks and in cultured cells reveal that UbcD1 directly controls Ci stability. Interestingly, UbcD1 is found to be selectively involved in Slimb-mediated Ci degradation. Finally, we show that the homologs of UbcD1 play a conserved role in modulating Hh signaling in vertebrates.
Genes / Markers
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Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes