cIAPs promote the proteasomal degradation of mutant SOD1 linked to familial amyotrophic lateral sclerosis.
Biochem Biophys Res Commun
; 480(3): 422-428, 2016 Nov 18.
Article
in En
| MEDLINE
| ID: mdl-27773815
ABSTRACT
Although the ubiquitin-proteasome system is believed to play an important role in the pathogenesis of familial amyotrophic lateral sclerosis (FALS), caused by mutations in Cu/Zn-superoxide dismutase 1 (SOD1), the mechanism of how mutant SOD1 protein is regulated in cells is still poorly understood. Here we have demonstrated that cellular inhibitor of apoptosis proteins (cIAPs) are specifically associated with FALS-linked mutant SOD1 (mSOD1) and that this interaction promotes the ubiquitin-dependent proteasomal degradation of mutant SOD1. By utilizing cumate inducible SOD1 cells, we also showed that knock-down or pharmacologic depletion of cIAPs leads to H2O2 induced cytotoxicity in mSOD1 expressing cells. Altogether, our results reveal a novel role of cIAPs in FALS-associated mutant SOD1 regulation.
Key words
Full text:
1
Database:
MEDLINE
Main subject:
Proteasome Endopeptidase Complex
/
Inhibitor of Apoptosis Proteins
/
Superoxide Dismutase-1
/
Amyotrophic Lateral Sclerosis
Limits:
Humans
Language:
En
Year:
2016
Type:
Article