Functional characterization of SAG/RBX2/ROC2/RNF7, an antioxidant protein and an E3 ubiquitin ligase  

作　　者：Yi Sun Hua Li 

机构地区：[1]Division of Radiation and Cancer Biology,Department of Radiation Oncology,University of Michigan,4424B Medical Science-I,1301 Catherine Street,Ann Arbor,MI 48109,USA.

出　　处：《Protein & Cell》2013年第2期103-116,共14页蛋白质与细胞（英文版）

基　　金：supported by the NCI grants(CA118762 and CA156744)to Yi Sun.

摘　　要：SAG(Sensitive to Apoptosis Gene),also known as RBX2(RING box protein 2),ROC2(Regulator of Cullins 2),or RNF7(RING Finger Protein 7),was originally cloned in our laboratory as a redox inducible antioxi-dant protein and later characterized as the second member of the RBX/ROC RING component of the SCF(SKP1-CUL-F-box Proteins)E3 ubiquitin ligase.When acting alone,SAG scavenges oxygen radicals by forming inter-and intra-molecular disulfide bonds,whereas by forming a complex with other components of the SCF E3 ligase,SAG promotes ubiquitination and degradation of a number of protein substrates,includ-ing c-JUN,DEPTOR,HIF-1α,IκBα,NF1,NOXA,p27,and procaspase-3,thus regulating various signaling path-ways and biological processes.Specifically,SAG pro-tects cells from apoptosis,confers radioresistance,and plays an essential and non-redundant role in mouse embryogenesis and vasculogenesis.Furthermore,stress-inducible SAG is overexpressed in a number of human cancers and SAG overexpression correlates with poor patient prognosis.Finally,SAG transgenic expression in epidermis causes an early stage inhibi-tion,but later stage promotion,of skin tumorigenesis triggered by DMBA/TPA.Given its major role in pro-moting targeted degradation of tumor suppressive proteins,leading to apoptosis suppression and accel-erated tumorigenesis,SAG E3 ligase appears to be an attractive anticancer target.

关 键 词：antioxidant angiogenesis apoptosis Cullin-RING ligases radiation resistance reactive oxygen species SAG/RBX2/ROC2/RNF7 SCF E3 ligases tumori-genesis ubiquitin ligase VASCULOGENESIS 

分 类 号：R73[医药卫生—肿瘤]