Regulation of SMN protein stability.

ABSTRACT: Spinal muscular atrophy (SMA) is caused by mutations of the survival of motor neuron (SMN1) gene and deficiency of full-length SMN protein (FL-SMN). All SMA patients retain one or more copies of the SMN2 gene, but the principal protein product of SMN2 lacks exon 7 (SMNDelta7) and is unable to compensate for a deficiency of FL-SMN. SMN is known to oligomerize and form a multimeric protein complex; however, the mechanisms regulating stability and degradation of FL-SMN and SMNDelta7 proteins have been largely unexplored. Using pulse-chase analysis, we characterized SMN protein turnover and confirmed that SMN was ubiquitinated and degraded by the ubiquitin proteasome system (UPS). The SMNDelta7 protein had a twofold shorter half-life than FL-SMN in cells despite similar intrinsic rates of turn

SUBMITTER: Burnett BG 

PROVIDER: S-EPMC2643817 | biostudies-literature | 2009 Mar

REPOSITORIES: biostudies-literature