Catalase Is Regulated by Ubiquitination and Proteosomal Degradation. Role of the c-Abl and Arg Tyrosine Kinases

Abstract

Catalase is a major effector in the defense of aerobic cells against oxidative stress. Recent studies have shown that catalase activity is stimulated by the c-Abl and Arg tyrosine kinases. Little, however, is otherwise known about the mechanisms responsible for catalase regulation. The present work demonstrates that mouse cells deficient in both c-Abl and Arg exhibit increased catalase stability. The results also show that catalase is subject to ubiquitination and degradation by the 26S proteosome. Significantly, ubiquitination of catalase is dependent on c-Abl- and Arg-mediated phosphorylation of catalase on both Y231 and Y386. In concert with these results, human 293 cells expressing catalase mutated at Y231 and Y386 exhibit attenuated levels of reactive oxygen species when exposed to hydrogen peroxide. These findings indicate that, in addition to stimulating catalase activity, c-Abl and Arg promote catalase degradation in the oxidative stress response.

Effects of calorie restriction on the expression of manganese superoxide dismutase and catalase under oxidative stress conditions in the rotifer Brachionus plicatilis

“…Such a discrepancy suggests that post-translational regulation contributes to the protein levels of these antioxidant enzymes under oxidative stress conditions. Indeed, it has been reported that the protein levels of Mn SOD [21] and catalase [22] are affected by the rate of degradation via the ubiquitin-proteasome pathway in mammals. In addition, quantitative experiments such as Western blotting would be useful to determine the precise expression levels of the antioxidant enzymes.…”

Proteasome inhibitor MG-132 induces C6 glioma cell apoptosis via oxidative stress

“…Therefore, oxidative stress could cause cell death via apoptotic pathways. Several studies have shown that oxidative stress is closely associated with the proteasome, as the proteasome is involved in regulating anti-oxidants, including catalase, heme oxygenase-1 (HO-1), copper/zinc-superoxide dismutase and γ-GCS [11][12][13][14] . However, the relationship between proteasome dysfunction and oxidative stress is still a matter of dispute.…”

Antioxidant status in women with uterine leiomyoma: relation with sex hormones

“…In addition to estrogen levels, cellular redox state may also influence CAT activity. It was observed that long-term oxidative stress reduces stability and half-life of catalase by stimulating ubiquitination and proteosomal degradation of the enzyme (Cao et al 2003). However, in maintenance of cellular H 2 O 2 levels, the harmonized CAT and GPX activity is most important since H 2 O 2 plays an important role in many physiological processes like cell cycle and proliferation (Li et al 2009), regulation of enzyme activity (Ferrer-Sueta et al 2011), redox signalling (Sies 2014) and apoptosis (Andrade et al 2013).…”