title: The genetics of 3-M syndrome: unravelling a potential new regulatory growth pathway.
abstract: 3-M syndrome is an autosomal recessive primordial growth disorder characterised by severe postnatal growth restriction caused by mutations in CUL7, OBSL1 or CCDC8. Clinical characteristics include dysmorphic facial features and fleshy prominent heels with a variable degree of radiological abnormalities. CUL7 is a structural protein central to the formation of an ubiquitin E3 ligase that is known to target insulin receptor substrate 1 for degradation. CUL7 also binds to p53 and may be involved in the control of p53-dependent apoptosis. OBSL1 is a cytoskeletal adaptor protein that was thought to play a central role in myocyte remodelling, and CCDC8 has no defined function as yet. However, the physical interaction of OBSL1 with both CUL7 and CCDC8 and its potential role in the regulation of CUL7 expression suggest all three proteins are members of the same growth-regulatory pathway. Future work should be directed to investigating the function of the 3-M syndrome pathway and in particular the role in the insulin like growth factor I signalling pathway with a view of potentially revealing new therapeutic targets and identifying key regulators of cellular growth.
authors.affiliation: Department of Endocrinology, Manchester Biomedical Centre, Manchester Academic Health Sciences Centre, School of Biomedicine, University of Manchester, Manchester, UK.
authors.forename: Dan
authors.initials: D
authors.lastname: Hanson
authors.forename: Philip G
authors.initials: PG
authors.lastname: Murray
authors.forename: Graeme C M
authors.initials: GC
authors.lastname: Black
authors.forename: Peter E
authors.initials: PE
authors.lastname: Clayton
mesh_terms: D000293:Adolescent; D041923:Adolescent Development; D000818:Animals; D001827:Body Height; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002648:Child; D002657:Child Development; D044842:Cullin Proteins / Q000235:genetics / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D004392:Dwarfism / Q000235:genetics* / Q000378:metabolism* / Q000503:physiopathology; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics* / Q000378:metabolism* / Q000503:physiopathology; D009123:Muscle Hypotonia / Q000235:genetics* / Q000378:metabolism* / Q000503:physiopathology; D050505:Mutant Proteins / Q000378:metabolism; D056730:Silver-Russell Syndrome / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D013131:Spine / Q000002:abnormalities / Q000378:metabolism / Q000503:physiopathology
chemical_list: C569196:CCDC8 protein, human; C506299:CUL7 protein, human; D002352:Carrier Proteins; D044842:Cullin Proteins; D003598:Cytoskeletal Proteins; D050505:Mutant Proteins; C522000:OBSL1 protein, human