The Genetics of 3-M Syndrome: Unravelling a Potential New Regulatory Growth Pathway
- 28 November 2011
- journal article
- review article
- Published by S. Karger AG in Hormone Research in Paediatrics
- Vol. 76 (6), 369-378
- https://doi.org/10.1159/000334392
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. Copyright (C) 2011 S. Karger AG, BaselKeywords
This publication has 37 references indexed in Scilit:
- Exome Sequencing Identifies CCDC8 Mutations in 3-M Syndrome, Suggesting that CCDC8 Contributes in a Pathway with CUL7 and OBSL1 to Control Human GrowthAmerican Journal of Human Genetics, 2011
- Structural insight into M-band assembly and mechanics from the titin-obscurin-like-1 complexProceedings of the National Academy of Sciences of the United States of America, 2010
- The Primordial Growth Disorder 3-M Syndrome Connects Ubiquitination to the Cytoskeletal Adaptor OBSL1American Journal of Human Genetics, 2009
- A large-scale mutation search reveals genetic heterogeneity in 3M syndromeEuropean Journal of Human Genetics, 2008
- The CUL7 E3 Ubiquitin Ligase Targets Insulin Receptor Substrate 1 for Ubiquitin-Dependent DegradationMolecular Cell, 2008
- Induction of Cullin 7 by DNA damage attenuates p53 functionProceedings of the National Academy of Sciences of the United States of America, 2007
- Obscurin-like 1, OBSL1, is a novel cytoskeletal protein related to obscurinGenomics, 2007
- Phosphorylation-Dependent Ubiquitination of Cyclin D1 by the SCFFBX4-αB Crystallin ComplexMolecular Cell, 2006
- Identification of mutations in CUL7 in 3-M syndromeNature Genetics, 2005
- Epimutation of the telomeric imprinting center region on chromosome 11p15 in Silver-Russell syndromeNature Genetics, 2005