Protein stability of mitochondrial superoxide dismutase SOD2 is regulated by USP36.
SOD2 is a key mitochondrial antioxidant enzyme and its perturbation leads to oxidative cell death, which results in various disorders. In this study, we identified a deubiquitinating enzyme USP36 that regulates the protein stability of SOD2. The regulatory effect of USP36 on SOD2 was initially identified by 2-DE and MALDI-TOF/MS analyses. In addition, endogenous USP36 and SOD2 were shown to interact in an immunoprecipitation assay, which was verified using the yeast two-hybrid system. Furthermore, we demonstrated that SOD2 binds with ubiquitin molecules to form polyubiquitination chains and undergoes degradation through the ubiquitin-proteasomal pathway. Finally, USP36 was shown to be a specific deubiquitinating enzyme that reduces the ubiquitination level of SOD2 and was involved in SOD2 protein stability by extending its half-life.
Department of Biomedical Science, CHA General Hospital, CHA University, Seoul, Republic of Korea.
Myung-Sun
MS
Kim
Suresh
S
Ramakrishna
Key-Hwan
KH
Lim
Jun-Hyun
JH
Kim
Kwang-Hyun
KH
Baek
D000818:Animals; D015153:Blotting, Western; D019556:COS Cells; D002460:Cell Line; D002522:Chlorocebus aethiops; D019295:Computational Biology; D015180:Electrophoresis, Gel, Two-Dimensional; D006367:HeLa Cells; D006801:Humans; D047468:Immunoprecipitation; D008928:Mitochondria / Q000201:enzymology*; D011485:Protein Binding / Q000235:genetics / Q000502:physiology; D055550:Protein Stability; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism*; D020798:Two-Hybrid System Techniques; D043222:Ubiquitin Thiolesterase / Q000235:genetics / Q000378:metabolism*; D054875:Ubiquitination / Q000235:genetics / Q000502:physiology; D000099156:Superoxide Dismutase 2
D013482:Superoxide Dismutase; D043222:Ubiquitin Thiolesterase; D000099156:Superoxide Dismutase 2; C501066:USP36 protein, human