The E3 ubiquitin ligase mind bomb 1 ubiquitinates and promotes the degradation of survival of motor neuron protein.
The E3 ubiquitin ligase mind bomb 1 ubiquitinates and promotes the degradation of survival of motor neuron protein.
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DOI：
10.1091/mbc.e13-01-0042
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发表时间：
2013-06
影响因子：
3.3
通讯作者：
Burnett BG
中科院分区：
文献类型：
--
作者：
Kwon DY;Dimitriadi M;Terzic B;Cable C;Hart AC;Chitnis A;Fischbeck KH;Burnett BG
Spinal muscular atrophy is caused by deficiency of the survival motor neuron (SMN) protein. We show that the E3 ubiquitin ligase, mind bomb 1 (Mib1), ubiquitinates and targets SMN for degradation. Reducing Mib1 increases SMN levels, and decreasing the Caenorhabditis elegans orthologue of Mib1 mitigates a neuromuscular defect characteristic of SMN deficiency. 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 (UPS). 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 (SMA) mice. Specific targets in the UPS 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 orthologue 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 SMA.
