PUBLICATION
UbcD1 regulates Hedgehog signaling by directly modulating Ci ubiquitination and processing
- Authors
- 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.
- ID
- ZDB-PUB-180719-12
- Date
- 2017
- Source
- EMBO reports 18: 1922-1934 (Journal)
- Registered Authors
- Liu, Feng
- Keywords
- Drosophila, Ci, Hedgehog, UbcD1, ubiquitination
- MeSH Terms
-
- Transcription Factors/genetics
- Transcription Factors/metabolism
- Zebrafish/genetics*
- Zebrafish/growth & development
- Zebrafish/metabolism
- Hedgehog Proteins/genetics*
- Hedgehog Proteins/metabolism
- Gene Expression Regulation, Developmental*
- DNA-Binding Proteins/genetics
- DNA-Binding Proteins/metabolism
- Embryo, Nonmammalian
- Protein Stability
- Patched-2 Receptor/genetics
- Patched-2 Receptor/metabolism
- Conserved Sequence
- Cell Cycle Proteins/genetics
- Cell Cycle Proteins/metabolism
- Ubiquitination
- Larva/genetics
- Larva/growth & development
- Larva/metabolism
- Signal Transduction
- Ubiquitin-Conjugating Enzymes/genetics*
- Ubiquitin-Conjugating Enzymes/metabolism
- Imaginal Discs/growth & development
- Imaginal Discs/metabolism
- Protein Processing, Post-Translational*
- Drosophila Proteins/genetics*
- Drosophila Proteins/metabolism
- Ubiquitin-Protein Ligases/genetics
- Ubiquitin-Protein Ligases/metabolism
- Animals
- Proteolysis
- Drosophila melanogaster/genetics*
- Drosophila melanogaster/growth & development
- Drosophila melanogaster/metabolism
- Polyubiquitin/genetics
- Polyubiquitin/metabolism
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- PubMed
- 28887318 Full text @ EMBO Rep.
Citation
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. (2017) UbcD1 regulates Hedgehog signaling by directly modulating Ci ubiquitination and processing. EMBO reports. 18:1922-1934.
Abstract
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
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping