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...

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...

Background: 3-M syndrome is an autosomal recessive disorder characterized by pre- and post-natal growth restriction, normal intelligence and dysmorphic facial features. Mutations in the genes encoding Cullin 7 (CUL7) and Obscurin like-1 (OBSL1) have been shown to cause 3-M syndrome.Aims: To characterize CUL7 production and localization in a primary fibroblast cell line from a patient with 3-M syndrome due to a CUL7 mutation and to assess cell prol...