The E3 ubiquitin ligase mind bomb 1 ubiquitinates and promotes the degradation of survival of motor neuron protein.

Spinal muscular atrophy is an inherited motor neuron disease that results from a deficiency of the survival of motor neuron (SMN) protein. SMN is ubiquitinated and degraded through the ubiquitin proteasome system. We have previously shown that proteasome inhibition increases SMN protein levels, improves motor function, and reduces spinal cord, ...
muscle, and neuromuscular junction pathology of spinal muscular atrophy mice. Specific targets in the ubiquitin-proteasome pathway may be more efficacious and less toxic. In this study, we show that the E3 ubiquitin ligase, mind bomb 1 (Mib1), interacts with and ubiquitinates SMN and facilitates its degradation. Knocking down Mib1 levels increases SMN protein levels in cultured cells. Also, knocking down the Mib1 ortholog improves neuromuscular function in Caenorhabditis elegans deficient in SMN. These findings demonstrate that Mib1 ubiquitinates and catalyzes the degradation of SMN, and thus represents a novel therapeutic target for spinal muscular atrophy.
Mol. Biol. Cell
Date: Apr. 24, 2013
Download Curated Data For This Publication
154767
Switch View:
  • Interactions 2
  • PTM Genes 2