Abstract
The posttranslational modification sumoylation can have multiple effects on its substrate proteins. We studied a patient with isolated cleft lip and palate and a balanced chromosomal translocation that disrupts the SUMO1 (small ubiquitin-related modifier) gene, resulting in haploinsufficiency. In mouse, we found that Sumo1 is expressed in the developing lip and palate and that a Sumo1 hypomorphic allele manifests an incompletely penetrant orofacial clefting phenotype. Products of several genes implicated in clefting are sumoylated, and the Sumo1 hypomorphic allele interacts genetically with a loss-of-function allele for one of these loci. Thus, sumoylation defines a network of genes important for palatogenesis.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Adult
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Animals
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Cell Line
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Child, Preschool
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Cleft Lip / genetics*
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Cleft Palate / genetics*
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Embryo, Mammalian / cytology
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Embryo, Mammalian / metabolism
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Gene Dosage
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Gene Expression Regulation, Developmental
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Humans
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In Situ Hybridization
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Intracellular Signaling Peptides and Proteins / genetics
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Intracellular Signaling Peptides and Proteins / metabolism
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Karyotyping
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Mice
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Mice, Inbred C57BL
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Morphogenesis
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Nuclear Proteins / genetics
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Nuclear Proteins / metabolism
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Palate / embryology
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Palate / metabolism
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Protein Tyrosine Phosphatases / genetics
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Protein Tyrosine Phosphatases / metabolism
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SUMO-1 Protein / genetics*
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SUMO-1 Protein / physiology
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Small Ubiquitin-Related Modifier Proteins / genetics*
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Small Ubiquitin-Related Modifier Proteins / physiology
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Stem Cells / metabolism
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Translocation, Genetic
Substances
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Intracellular Signaling Peptides and Proteins
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Nuclear Proteins
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SUMO-1 Protein
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SUMO1 protein, human
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Small Ubiquitin-Related Modifier Proteins
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Eya1 protein, mouse
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Protein Tyrosine Phosphatases