Novel polymorphisms of nuclear receptor SHP associated with functional and structural changes.

ABSTRACT: We identified three heterozygous nonsynonymous single nucleotide polymorphisms in the small heterodimer partner (SHP, NROB2) gene in normal subjects and CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy)-like patients, including two novel missense mutations (p.R38H, p.K170N) and one of the previously reported polymorphism (p.G171A). Four novel heterozygous mutations were also identified in the intron ((Intron)1265T-->A), 3'-untranslated region ((3'-UTR)101C-->G, (3'-UTR)186T-->C), and promoter ((Pro)-423C-->T) of the SHP gene. The exonic R38H and K170N mutants exhibited impaired nuclear translocation. K170N made SHP more susceptible to ubiquitination mediated degradation and blocked SHP acetylation, which displayed lost repressive activity

SUBMITTER: Zhou T 

PROVIDER: S-EPMC2915723 | biostudies-literature | 2010 Aug

REPOSITORIES: biostudies-literature