CRL4Mahj E3 ubiquitin ligase promotes neural stem cell reactivation
| Autor: | Yingjie Zhang, Wu-Min Deng, Fengwei Yu, Gengqiang Xie, Sharyn A. Endow, Ye Sing Tan, Chwee Tat Koe, Phuong Thao Ly, Hongyan Wang |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Biochemistry Animals Genetically Modified Ligases RNA interference 0302 clinical medicine Neural Stem Cells Ubiquitin Drosophila Proteins Post-Translational Modification Biology (General) chemistry.chemical_classification biology Drosophila Melanogaster General Neuroscience Ubiquitin-Protein Ligase Complexes Eukaryota Animal Models Cullin Proteins Neural stem cell Enzymes Precipitation Techniques 3. Good health Ubiquitin ligase Cell biology DNA-Binding Proteins Insects Nucleic acids Experimental Organism Systems Genetic interference Cell Processes Hyperexpression Techniques Drosophila Epigenetics General Agricultural and Biological Sciences Protein Binding Signal Transduction Research Article Arthropoda Immunoprecipitation QH301-705.5 Ubiquitin-Protein Ligases Research and Analysis Methods General Biochemistry Genetics and Molecular Biology 03 medical and health sciences DDB1 Model Organisms Genetics Gene Expression and Vector Techniques Animals Humans Molecular Biology Techniques Molecular Biology Molecular Biology Assays and Analysis Techniques Hippo signaling pathway DNA ligase General Immunology and Microbiology Ubiquitination Organisms Biology and Life Sciences Proteins Cell Biology Invertebrates 030104 developmental biology chemistry nervous system Animal Studies Enzymology biology.protein RNA Gene expression Carrier Proteins 030217 neurology & neurosurgery |
| Zdroj: | PLoS Biology, Vol 17, Iss 6, p e3000276 (2019) PLoS Biology |
| ISSN: | 1545-7885 1544-9173 |
| Popis: | The ability of neural stem cells (NSCs) to transit between quiescence and proliferation is crucial for brain development and homeostasis. Drosophila Hippo pathway maintains NSC quiescence, but its regulation during brain development remains unknown. Here, we show that CRL4Mahj, an evolutionarily conserved E3 ubiquitin ligase, is essential for NSC reactivation (exit from quiescence). We demonstrate that damaged DNA-binding protein 1 (DDB1) and Cullin4, two core components of Cullin4-RING ligase (CRL4), are intrinsically required for NSC reactivation. We have identified a substrate receptor of CRL4, Mahjong (Mahj), which is necessary and sufficient for NSC reactivation. Moreover, we show that CRL4Mahj forms a protein complex with Warts (Wts/large tumor suppressor [Lats]), a kinase of the Hippo signaling pathway, and Mahj promotes the ubiquitination of Wts. Our genetic analyses further support the conclusion that CRL4Mahj triggers NSC reactivation by inhibition of Wts. Given that Cullin4B mutations cause mental retardation and cerebral malformation, similar regulatory mechanisms may be applied to the human brain. During the transition from quiescence to reactivation of neural stem cells, the E3 ubiquitin ligase CRL4Mahj promotes their reactivation by inhibiting Wts, a core kinase of Hippo signalling pathway. |
| Databáze: | OpenAIRE |
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