| Functional characterization of SAG/RBX2/ROC2/RNF7, an antioxidant protein and an E3 ubiquitin ligase. | |
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MedLine Citation:
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PMID: 23136067 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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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 antioxidant 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, including c-JUN, DEPTOR, HIF-1α, IκBα, NF1, NOXA, p27, and procaspase-3, thus regulating various signaling pathways and biological processes. Specifically, SAG protects 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 inhibition, but later stage promotion, of skin tumorigenesis triggered by DMBA/TPA. Given its major role in promoting targeted degradation of tumor suppressive proteins, leading to apoptosis suppression and accelerated tumorigenesis, SAG E3 ligase appears to be an attractive anticancer target. |
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Authors:
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Yi Sun; Hua Li |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-11-8 |
Journal Detail:
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Title: Protein & cell Volume: - ISSN: 1674-8018 ISO Abbreviation: Protein Cell Publication Date: 2012 Nov |
Date Detail:
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Created Date: 2012-11-8 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101532368 Medline TA: Protein Cell Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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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, sunyi@umich.edu. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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