Endocrine Abstracts

Ubiquitination (Ub) is the process that controls the level and activity of cellular proteins. Mono-ubiquitination of a protein alters its function, while poly-ubiquitination targets a protein for degradation (as the ‘kiss of death’). Alterations in the Ub system are associated with a wide range of disease, e.g. cancer, neurological diseases and viral infection.Disorders of growth where the phenotype is primarily short stature are usually caused...

Background: 3-M syndrome is associated with severe proportionate pre- and postnatal growth restriction, and is caused by mutations in CUL7, OBSL1, or CCDC8 genes.Aims and methods: To define baseline growth and GH–IGF1 axis status as well as response to r-hGH in relation to mutation status in 3-M children, using retrospective analysis of data from clinical notes.Results: 50 individuals (19 CUL7, 19 <...

3-M syndrome is characterised by post-natal growth restriction. We have identified causative mutations in three genes CUL7, OBSL1 and CCDC8. CUL7, a component of an E3 ubiquitin ligase, has a binding domain for p53 and its reduction or absence has a major impact on growth and cell division. OBSL1 is postulated to have a role as a cytoskeletal adaptor, and was not recognised previously to be a growth regulator. The domain structure of CCDC8 predicts a possi...