title: A dominant-negative form of the E3 ubiquitin ligase Cullin-1 disrupts the correct allocation of cell fate in the neural crest lineage.
abstract: Selective protein degradation is an efficient and rapid way of terminating protein activity. Defects in protein degradation are associated with a number of human diseases, including potentially DiGeorge syndrome, which is characterised by abnormal development of the neural crest lineage during embryogenesis. We describe the identification of Xenopus Cullin-1, an E3 ubiquitin ligase, and show that blocking the function of endogenous Cullin-1 leads to pleiotropic defects in development. Notably, there is an increased allocation of cells to a neural crest fate and within this lineage, an increase in melanocytes at the expense of cranial ganglia neurons. Most of the observed effects can be attributed to stabilisation of beta-catenin, a known target of Cullin-1-mediated degradation from other systems. Indeed, we show that blocking the function of Cullin-1 leads to a decrease in ubiquitinated beta-catenin and an increase in total beta-catenin. Our results show that Cullin-1-mediated protein degradation plays an essential role in the correct allocation of neural crest fates during embryogenesis.
authors.affiliation: The Wellcome Trust/Cancer Research UK Gurdon Institute, Cambridge.
authors.forename: Jana
authors.initials: J
authors.lastname: Voigt
authors.forename: Nancy
authors.initials: N
authors.lastname: Papalopulu
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D019070:Cell Lineage; D044842:Cullin Proteins / Q000235:genetics / Q000378:metabolism*; D004062:DiGeorge Syndrome / Q000473:pathology; D004625:Embryo, Nonmammalian / Q000002:abnormalities / Q000033:anatomy & histology / Q000502:physiology; D047108:Embryonic Development; D005724:Ganglia / Q000166:cytology / Q000378:metabolism; D006801:Humans; D008544:Melanocytes / Q000166:cytology / Q000378:metabolism; D008969:Molecular Sequence Data; D009432:Neural Crest / Q000166:cytology* / Q000502:physiology; D010641:Phenotype; D016415:Sequence Alignment; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism; D014982:Xenopus laevis / Q000033:anatomy & histology / Q000196:embryology / Q000378:metabolism; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
chemical_list: D015415:Biomarkers; D018797:Cell Cycle Proteins; C100318:Cullin 1; D044842:Cullin Proteins; D029867:Xenopus Proteins; D051176:beta Catenin