A dominant-negative form of the E3 ubiquitin ligase Cullin-1 disrupts the correct allocation of cell fate in the neural crest lineage.
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.
Voigt
Jana
J
The Wellcome Trust/Cancer Research UK Gurdon Institute, Cambridge.
Papalopulu
Nancy
N
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
D015415:Biomarkers; D018797:Cell Cycle Proteins; C100318:Cullin 1; D044842:Cullin Proteins; D029867:Xenopus Proteins; D051176:beta Catenin