Document Detail


Functional characterization of SAG/RBX2/ROC2/RNF7, an antioxidant protein and an E3 ubiquitin ligase.
MedLine Citation:
PMID:  23136067     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Yi Sun; Hua Li
Related Documents :
23036787 - Uncoupling protein 1 dependent reactive oxygen species production by thymus mitochondria.
18585437 - Effects of cycloheximide on extinction in an appetitively motivated operant conditionin...
25060237 - Multi-protein assemblies underlie the mesoscale organization of the plasma membrane.
24685647 - Comparative proteomic analysis of anti-cancer mechanism by periplocin treatment in lung...
22399757 - Fbl2 regulates amyloid precursor protein (app) metabolism by promoting ubiquitination-d...
17495517 - Autophagy during conidiation, conidial germination and turgor generation in magnaporthe...
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Review     Date:  2012-11-08
Journal Detail:
Title:  Protein & cell     Volume:  4     ISSN:  1674-8018     ISO Abbreviation:  Protein Cell     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-03-12     Completed Date:  2013-09-06     Revised Date:  2014-04-08    
Medline Journal Info:
Nlm Unique ID:  101532368     Medline TA:  Protein Cell     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  103-16     Citation Subset:  IM    
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Animals
Antioxidants / metabolism
Apoptosis
Carrier Proteins / chemistry,  genetics,  metabolism*
Cell Transformation, Neoplastic
Humans
RING Finger Domains
Substrate Specificity
Ubiquitin-Protein Ligases / chemistry,  metabolism*
Ubiquitination
Grant Support
ID/Acronym/Agency:
CA118762/CA/NCI NIH HHS; CA156744/CA/NCI NIH HHS; R01 CA118762/CA/NCI NIH HHS; R21 CA170995/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Antioxidants; 0/Carrier Proteins; EC 6.3.2.19/Ubiquitin-Protein Ligases
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Intersection of autophagy with pathways of antigen presentation.
Next Document:  Endoreduplication intensity as a marker of seed developmental stage in the Fabaceae.