RRC ID 49271
Author 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.
Title UbcD1 regulates Hedgehog signaling by directly modulating Ci ubiquitination and processing.
Journal EMBO Rep.
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.
Volume 18(11)
Pages 1922-1934
Published 2017-11
DOI 10.15252/embr.201643289
PII embr.201643289
PMID 28887318
PMC PMC5666607
MeSH 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
IF 8.383
Resource
Drosophila 7425R-1 9924R-1