Differential roles of proteasome and immunoproteasome regulators Pa28¦Á¦Â, Pa28¦Ã and Pa200 in the degradation of oxidized proteins

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• 作者：Andrew M. Pickering ; Kelvin J.A. Davies ; ^{kelvin@usc.edu}
• 关键词：Oxidative stress adaptation (hormesis) ; Ubiquitin&ndash ; proteasome system ; Protein degradation ; Proteasome regulators ; Pa28 (11S) regulator ; Immunoproteasome
• 刊名：Archives of Biochemistry and Biophysics
• 出版年：2012
• 出版时间：15 July, 2012
• 年：2012
• 卷：523
• 期：2
• 页码：181-190
• 全文大小：1427 K

文摘

The response and functions of proteasome regulators Pa28¦Á¦Â (or 11S), Pa28¦Ã and Pa200 in oxidative-stress adaptation (also called hormesis) was studied in murine embryonic fibroblasts (MEFs), using a well-characterized model of cellular adaptation to low concentrations (1.0-10.0 ¦ÌM) of hydrogen peroxide (H₂O₂), which alter gene expression profiles, increasing resistance to higher levels of oxidative-stress. Pa28¦Á¦Â bound to 20S proteasomes immediately upon H₂O₂-treatment, whereas 26S proteasomes were disassembled at the same time. Over the next 24 h, the levels of Pa28¦Á¦Â, Pa28¦Ã and Pa200 proteasome regulators increased during H₂O₂-adaptation, whereas the 19S regulator was unchanged. Purified Pa28¦Á¦Â, and to a lesser extent Pa28¦Ã, significantly increased the ability of purified 20S proteasome to selectively degrade oxidized proteins; Pa28¦Á¦Â also increased the capacity of purified immunoproteasome to selectively degrade oxidized proteins but Pa28¦Ã did not. Pa200 regulator actually decreased 20S proteasome and immunoproteasome¡¯s ability to degrade oxidized proteins but Pa200 and poly-ADP ribose polymerase may cooperate in enabling initiation of DNA repair. Our results indicate that cytoplasmic Pa28¦Á¦Â and nuclear Pa28¦Ã may both be important regulators of proteasome¡¯s ability to degrade oxidatively-damaged proteins, and induced-expression of both 20S proteasome and immunoproteasome, and their Pa28¦Á¦Â and Pa28¦Ã regulators are important for oxidative-stress adaptation.