COP9 signalosome subunits protect Capicua from MAP kinase-dependent and independent mechanisms of degradation
| Autor: | Jessica E. Treisman, Kevin Legent, DanQing He, Annabelle Suisse |
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| Rok vydání: | 2017 |
| Předmět: |
Male
0301 basic medicine MAP Kinase Signaling System Protein subunit Genes Insect Eye Models Biological NEDD8 Animals Genetically Modified 03 medical and health sciences Ubiquitin HMGB Proteins Animals Drosophila Proteins Wings Animal Epidermal growth factor receptor COP9 signalosome Receptors Invertebrate Peptide Molecular Biology biology COP9 Signalosome Complex Ubiquitination Cullin Proteins Molecular biology Ubiquitin ligase Cell biology ErbB Receptors Repressor Proteins Protein Subunits Drosophila melanogaster 030104 developmental biology Multiprotein Complexes Mutation Proteolysis biology.protein Female Ectopic expression Cullin Peptide Hydrolases Research Article Developmental Biology |
| Zdroj: | Development. |
| ISSN: | 1477-9129 0950-1991 |
| Popis: | The COP9 signalosome removes Nedd8 modifications from the Cullin subunits of ubiquitin ligase complexes, reducing their activity. Here we show that mutations in the Drosophila COP9 signalosome subunit 1b (CSN1b) gene increase the activity of ubiquitin ligases that contain Cullin 1. Analysis of CSN1b mutant phenotypes revealed a requirement for the COP9 signalosome to prevent ectopic expression of Epidermal growth factor receptor (EGFR) target genes. It does so by protecting Capicua, a transcriptional repressor of EGFR target genes, from EGFR pathway-dependent ubiquitination by a Cullin 1/SKP1-related A/Archipelago E3 ligase and subsequent proteasomal degradation. The CSN1b subunit also maintains basal Capicua levels by protecting it from a separate mechanism of degradation that is independent of EGFR signaling. As a suppressor of tumor growth and metastasis, Capicua may be an important target of the COP9 signalosome in cancer. |
| Databáze: | OpenAIRE |
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