title: Sumoylation in Craniofacial Disorders.
abstract: Craniofacial development requires a complex series of coordinated and finely tuned events to take place, during a relatively short time frame. These events are set in motion by switching on and off transcriptional cascades that involve the use of numerous signalling pathways and a multitude of factors that act at the site of gene transcription. It is now well known that amidst the subtlety of this process lies the intricate world of protein modification, and the posttranslational addition of the small ubiquitin -like modifier, SUMO, is an example that has been implicated in this process. Many proteins that are required for formation of various structures in the embryonic head and face adapt specific functions with SUMO modification. Interestingly, the main clinical phenotype reported for a disruption of the SUMO1 locus is the common birth defect cleft lip and palate. In this chapter therefore, we discuss the role of SUMO1 in craniofacial development, with emphasis on orofacial clefts. We suggest that these defects can be a sensitive indication of down regulated SUMO modification at a critical stage during embryogenesis. As well as specific mutations affecting the ability of particular proteins to be sumoylated, non-genetic events may have the effect of down-regulating the SUMO pathway to give the same result. Enzymes regulating the SUMO pathway may become important therapeutic targets in the preventative and treatment therapies for craniofacial defects in the future.
authors.affiliation: Institute of Child Health, University College London, 30 Guilford Street, London, WC1N 1EH, UK.
authors.forename: Erwin
authors.initials: E
authors.lastname: Pauws
authors.affiliation: Institute of Child Health, University College London, 30 Guilford Street, London, WC1N 1EH, UK. p.stanier@ucl.ac.uk.
authors.forename: Philip
authors.initials: P
authors.lastname: Stanier
mesh_terms: D000818:Animals; D002971:Cleft Lip / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D002972:Cleft Palate / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D019465:Craniofacial Abnormalities / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D020022:Genetic Predisposition to Disease; D006801:Humans; D010641:Phenotype; D012307:Risk Factors; D025842:SUMO-1 Protein; D015398:Signal Transduction; D025841:Small Ubiquitin-Related Modifier Proteins / Q000235:genetics / Q000378:metabolism*; D058207:Sumoylation; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*
chemical_list: D025842:SUMO-1 Protein; C495501:SUMO1 protein, human; D025841:Small Ubiquitin-Related Modifier Proteins; D044767:Ubiquitin-Protein Ligases
keywords: Cleft lip and palate; Craniofacial development; SUMO; Stress; Transcription