Catalase is regulated by ubiquitination and proteosomal degradation. Role of the c-Abl and Arg tyrosine kinases.
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.
Cao
Cheng
C
Beijing Institute of Biotechnology, Beijing 100850, Peoples Republic of China.
Leng
Yumei
Y
Liu
Xuan
X
Yi
Yanping
Y
Li
Ping
P
Kufe
Donald
D
D000818:Animals; D002374:Catalase / Q000378:metabolism*; D002460:Cell Line; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D004789:Enzyme Activation; D004795:Enzyme Stability; D006801:Humans; D051379:Mice; D009097:Multienzyme Complexes / Q000378:metabolism*; D018384:Oxidative Stress; D010766:Phosphorylation; D046988:Proteasome Endopeptidase Complex; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D016315:Proto-Oncogene Proteins c-abl / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D025801:Ubiquitin / Q000378:metabolism*
D009097:Multienzyme Complexes; D017382:Reactive Oxygen Species; D025801:Ubiquitin; D002374:Catalase; C426236:ARG tyrosine kinase; D011505:Protein-Tyrosine Kinases; D016315:Proto-Oncogene Proteins c-abl; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex