期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 287, 期 52, 页码 43741-43752出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M112.372318
关键词
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资金
- National Institutes of Health [5RO1NS72397]
- American-Syrian-Lebanese Associated Charities
- Cancer League of Colorado
- NIH/NCRR Colorado CTSI Grant [UL1 RR025780]
Spinal muscular atrophy (SMA), the leading genetic disorder of infant mortality, is caused by low levels of survival motor neuron (SMN) protein. Currently it is not clear how the SMN protein levels are regulated at the post-transcriptional level. In this report, we find that Usp9x, a deubiquitinating enzyme, stably associates with the SMN complex via directly interacting with SMN. Usp9x deubiquitinates SMN that is mostly mono-and di-ubiquitinated. Knockdown of Usp9x promotes SMN degradation and reduces the protein levels of SMN and the SMN complex in cultured mammalian cells. Interestingly, Usp9x does not deubiquitinate nuclear SMN Delta 7, the main protein product of the SMN2 gene, which is polyubiquitinated and rapidly degraded by the proteasome. Together, our results indicate that SMN and SMN Delta 7 are differently ubiquitinated; Usp9x plays an important role in stabilizing SMN and the SMN complex, likely via antagonizing Ub-dependent SMN degradation.
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