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المؤلفون: Maikel P. Peppelenbosch, Anke Brouwers, Judith T.M.L. Paridaen, Vincent Runtuwene, Sander H. Diks, Danica Zivkovic, Maria A. Sartori da Silva, Jin-Ming Tee, Daniele Guardavaccaro
المساهمون: Molecular Neuroscience and Ageing Research (MOLAR), Stem Cell Aging Leukemia and Lymphoma (SALL), Hubrecht Institute for Developmental Biology and Stem Cell Research, Gastroenterology & Hepatology
المصدر: PLoS ONE, 5(11):14023. PUBLIC LIBRARY SCIENCE
PLoS ONE, Vol 5, Iss 11, p e14023 (2010)
PLoS One, 5(11). Public Library of Science
PLoS One (print), 5(11). Public Library of Science
PLoS ONEمصطلحات موضوعية: Embryo, Nonmammalian, lcsh:Medicine, Suppressor of Cytokine Signaling Proteins, 0302 clinical medicine, Receptors, Developmental Biology/Developmental Molecular Mechanisms, Basic Helix-Loop-Helix Transcription Factors, UBIQUITIN LIGASES, an Elongin BC adaptor and a cullin (Cul2 or Cul5) scaffold which interacts with the RING protein. In vitro studies have shown that the conserved amino acid sequence of the cullin box in SOCS-box proteins is required for complex formation and function. However, Developmental, lcsh:Science, Non-U.S. Gov't, PHOSPHORYLATION, Zebrafish, Animals, Binding Sites, Cell Proliferation, Cullin Proteins, Gene Expression Regulation, Developmental, Green Fluorescent Proteins, Immunoblotting, In Situ Hybridization, Intracellular Signaling Peptides and Proteins, Membrane Proteins, Microscopy, Confocal, Mutation, Neurons, Receptors, Notch, Reverse Transcriptase Polymerase Chain Reaction, Zebrafish Proteins, Signal Transduction, NEUROGENIN1, Microscopy, 0303 health sciences, Nonmammalian, Multidisciplinary, biology, Research Support, Non-U.S. Gov't, CUL5-RBX2 MODULES, ANKYRIN REPEAT, Cell biology, Notch proteins, we isolated a zebrafish mutant lacking the Cul5 box (Asb11Cul). We found that homozygous zebrafish mutants for this allele were defective in Notch signaling as indicated by the impaired expression of Notch target genes. Importantly, Embryo, proper cell fate specification within the neurogenic regions of the zebrafish embryo was impaired. In addition, Confocal, embryonic structures, PROTEIN-SYNTHESIS, asb11Cul fish were not capable to degrade the Notch ligand DeltaA during embryogenesis, CUL5, Cullin, Research Article, ECS (Elongin BC-Cul2/Cul5-SOCS-box protein) ubiquitin ligases recruit substrates to E2 ubiquitin-conjugating enzymes through a SOCS-box protein substrate receptor, an Elongin BC adaptor and a cullin (Cul2 or Cul5) scaffold which interacts with the RING protein. In vitro studies have shown that the conserved amino acid sequence of the cullin box in SOCS-box proteins is required for complex formation and function. However, the in vivo importance of cullin boxes has not been addressed. To explore the biological functions of the cullin box domain of ankyrin repeat and SOCS-box containing protein 11 (d-Asb11), a key mediator of canonical Delta-Notch signaling, we isolated a zebrafish mutant lacking the Cul5 box (Asb11Cul). We found that homozygous zebrafish mutants for this allele were defective in Notch signaling as indicated by the impaired expression of Notch target genes. Importantly, asb11Cul fish were not capable to degrade the Notch ligand DeltaA during embryogenesis, a process essential for the initiation of Notch signaling during neurogenesis. Accordingly, proper cell fate specification within the neurogenic regions of the zebrafish embryo was impaired. In addition, Asb11Cul mRNA was defective in the ability to transactivate a her4::gfp reporter DNA when injected in embryos. Thus, our study reporting the generation and the characterization of a metazoan organism mutant in the conserved cullin binding domain of the SOCS-box demonstrates a hitherto unrecognized importance of the SOCS-box domain for the function of this class of cullin-RING ubiquitin ligases and establishes that the d-Asb11 cullin box is required for both canonical Notch signaling and proper neurogenesis, EXPRESSION, Notch, our study reporting the generation and the characterization of a metazoan organism mutant in the conserved cullin binding domain of the SOCS-box demonstrates a hitherto unrecognized importance of the SOCS-box domain for the function of this class of cullin-RING ubiquitin ligases and establishes that the d-Asb11 cullin box is required for both canonical Notch signaling and proper neurogenesis, Cell Biology/Developmental Molecular Mechanisms, Notch signaling pathway, SOCS-BOX, Cell fate determination, Asb11Cul mRNA was defective in the ability to transactivate a her4::gfp reporter DNA when injected in embryos. Thus, Research Support, 03 medical and health sciences, Journal Article, 030304 developmental biology, the in vivo importance of cullin boxes has not been addressed. To explore the biological functions of the cullin box domain of ankyrin repeat and SOCS-box containing protein 11 (d-Asb11), a process essential for the initiation of Notch signaling during neurogenesis. Accordingly, lcsh:R, fungi, ZEBRAFISH EMBRYOS, Chemical Biology/Chemical Biology of the Cell, biology.organism_classification, GENE, ECS (Elongin BC-Cul2/Cul5-SOCS-box protein) ubiquitin ligases recruit substrates to E2 ubiquitin-conjugating enzymes through a SOCS-box protein substrate receptor, a key mediator of canonical Delta-Notch signaling, Gene Expression Regulation, biology.protein, lcsh:Q, Ankyrin repeat, 030217 neurology & neurosurgery
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