cIAPs promote the proteasomal degradation of mutant SOD1 linked to familial amyotrophic lateral sclerosis.

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.

• Authors: Jin Sun Choi, Kidae Kim, Do Hee Lee, Sayeon Cho, Jae Du Ha, Byoung Chul Park, Sunhong Kim, Sung Goo Park, Jeong-Hoon Kim
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 480 Issue 3 Pg. 422-428 (Nov 18 2016) ISSN: 1090-2104 [Electronic] United States
• PMID: 27773815 (Publication Type: Journal Article)
• Copyright: Copyright © 2016 Elsevier Inc. All rights reserved.

Chemical References

• Inhibitor of Apoptosis Proteins
• SOD1 protein, human
• Superoxide Dismutase-1
• Proteasome Endopeptidase Complex

Topics

• Amyotrophic Lateral Sclerosis (genetics, metabolism)
• HEK293 Cells
• Humans
• Inhibitor of Apoptosis Proteins (metabolism)
• Mutation (genetics)
• Proteasome Endopeptidase Complex (metabolism)
• Superoxide Dismutase-1 (genetics, metabolism)
• Ubiquitination