Previous Article | Next Article 
Molecular and Cellular Biology, April 1999, p. 3145-3155, Vol. 19, No. 4
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
SAG, a Novel Zinc RING Finger Protein That Protects
Cells from Apoptosis Induced by Redox Agents
Hangjun
Duan,1
Yuli
Wang,1
Micheal
Aviram,2,
Manju
Swaroop,1
Joseph A.
Loo,3
Junhui
Bian,1,
Ye
Tian,1
Tom
Mueller,1
Charles L.
Bisgaier,2,§ and
Yi
Sun1,*
Departments of Molecular
Biology,1 Cardiac and Vascular
Diseases,2 and
Chemistry,3 Parke-Davis
Pharmaceutical Research, Division of Warner-Lambert Company, Ann
Arbor, Michigan 48105
Received 18 November 1998/Returned for modification 22 December
1998/Accepted 11 January 1999
SAG (sensitive to apoptosis gene) was cloned as an
inducible gene by 1,10-phenanthroline (OP), a redox-sensitive compound and an apoptosis inducer. SAG encodes a novel zinc RING
finger protein that consists of 113 amino acids with a calculated
molecular mass of 12.6 kDa. SAG is highly conserved during evolution,
with identities of 70% between human and Caenorhabditis
elegans sequences and 55% between human and yeast sequences. In
human tissues, SAG is ubiquitously expressed at high levels
in skeletal muscles, heart, and testis. SAG is localized in both the
cytoplasm and the nucleus of cells, and its gene was mapped to
chromosome 3q22-24. Bacterially expressed and purified human SAG binds
to zinc and copper metal ions and prevents lipid peroxidation induced
by copper or a free radical generator. When overexpressed in several
human cell lines, SAG protects cells from apoptosis induced by redox agents (the metal chelator OP and zinc or copper metal ions). Mechanistically, SAG appears to inhibit and/or delay metal ion-induced cytochrome c release and caspase activation. Thus, SAG is a
cellular protective molecule that appears to act as an antioxidant to
inhibit apoptosis induced by metal ions and reactive oxygen species.
*
Corresponding author. Mailing address: Department of
Molecular Biology, Parke-Davis Pharmaceutical Research, Division of
Warner-Lambert Company, 2800 Plymouth Road, Ann Arbor, MI 48105. Phone:
(734) 622-1959. Fax: (734) 622-7158. E-mail:
yi.sun{at}wl.com.

Present address: Lipid Research Laboratory, Rambam Medical Center,
Bat-Galim, Haifa 31096,
Israel.

Present address: Abilene Christian University, Abilene, TX
79699.
§
Present address: Esperion Therapeutic, Inc., Ann Arbor, MI
48108.
Molecular and Cellular Biology, April 1999, p. 3145-3155, Vol. 19, No. 4
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
This article has been cited by other articles:
-
Tan, M., Davis, S. W., Saunders, T. L., Zhu, Y., Sun, Y.
(2009). RBX1/ROC1 disruption results in early embryonic lethality due to proliferation failure, partially rescued by simultaneous loss of p27. Proc. Natl. Acad. Sci. USA
106: 6203-6208
[Abstract]
[Full Text]
-
He, H., Gu, Q., Zheng, M., Normolle, D., Sun, Y.
(2008). SAG/ROC2/RBX2 E3 ligase promotes UVB-induced skin hyperplasia, but not skin tumors, by simultaneously targeting c-Jun/AP-1 and p27. Carcinogenesis
29: 858-865
[Abstract]
[Full Text]
-
Gu, Q., Bowden, G. T., Normolle, D., Sun, Y.
(2007). SAG/ROC2 E3 ligase regulates skin carcinogenesis by stage-dependent targeting of c-Jun/AP1 and I{kappa}B-{alpha}/NF-{kappa}B. JCB
178: 1009-1023
[Abstract]
[Full Text]
-
Gu, Q., Tan, M., Sun, Y.
(2007). SAG/ROC2/Rbx2 Is a Novel Activator Protein-1 Target that Promotes c-Jun Degradation and Inhibits 12-O-Tetradecanoylphorbol-13-Acetate-Induced Neoplastic Transformation. Cancer Res.
67: 3616-3625
[Abstract]
[Full Text]
-
Blackstone, N. W., Bridge, D. M.
(2005). Model Systems for Environmental Signaling. Integr. Comp. Biol.
45: 605-614
[Abstract]
[Full Text]
-
Furukawa, M., Xiong, Y.
(2005). BTB Protein Keap1 Targets Antioxidant Transcription Factor Nrf2 for Ubiquitination by the Cullin 3-Roc1 Ligase. Mol. Cell. Biol.
25: 162-171
[Abstract]
[Full Text]
-
Donaldson, T. D., Noureddine, M. A., Reynolds, P. J., Bradford, W., Duronio, R. J.
(2004). Targeted Disruption of Drosophila Roc1b Reveals Functional Differences in the Roc Subunit of Cullin-dependent E3 Ubiquitin Ligases. Mol. Biol. Cell
15: 4892-4903
[Abstract]
[Full Text]
-
Kim, Y.-S., Lee, J.-Y., Son, M.-Y., Park, W., Bae, Y.-S.
(2003). Phosphorylation of Threonine 10 on CKBBP1/SAG/ROC2/Rbx2 by Protein Kinase CKII Promotes the Degradation of I{kappa}B{alpha} and p27Kip1. J. Biol. Chem.
278: 28462-28469
[Abstract]
[Full Text]
-
Li, J., Jiang, P., Robinson, M., Lawrence, T. S., Sun, Y.
(2003). AMPK-{beta}1 subunit is a p53-independent stress responsive protein that inhibits tumor cell growth upon forced expression. Carcinogenesis
24: 827-834
[Abstract]
[Full Text]
-
Huang, Y., Tan, M., Gosink, M., Wang, K. K. W., Sun, Y.
(2002). Histone Deacetylase 5 Is Not a p53 Target Gene, But Its Overexpression Inhibits Tumor Cell Growth and Induces Apoptosis. Cancer Res.
62: 2913-2922
[Abstract]
[Full Text]
-
Cornu, T. I., de la Torre, J. C.
(2001). RING Finger Z Protein of Lymphocytic Choriomeningitis Virus (LCMV) Inhibits Transcription and RNA Replication of an LCMV S-Segment Minigenome. J. Virol.
75: 9415-9426
[Abstract]
[Full Text]
-
Tan, M., Bian, J., Guan, K., Sun, Y.
(2001). p53CP is p51/p63, the third member of the p53 gene family: partial purification and characterization. Carcinogenesis
22: 295-300
[Abstract]
[Full Text]
-
Wu, K., Fuchs, S. Y., Chen, A., Tan, P., Gomez, C., Ronai, Z.'e., Pan, Z.-Q.
(2000). The SCFHOS/beta -TRCP-ROC1 E3 Ubiquitin Ligase Utilizes Two Distinct Domains within CUL1 for Substrate Targeting and Ubiquitin Ligation. Mol. Cell. Biol.
20: 1382-1393
[Abstract]
[Full Text]
-
Tan, M., Wang, Y., Guan, K., Sun, Y.
(2000). PTGF-beta , a type beta transforming growth factor (TGF-beta ) superfamily member, is a p53 target gene that inhibits tumor cell growth via TGF-beta signaling pathway. Proc. Natl. Acad. Sci. USA
97: 109-114
[Abstract]
[Full Text]
-
Sun, Y.
(1999). Alterations of SAG mRNA in human cancer cell lines: requirement for the RING finger domain for apoptosis protection. Carcinogenesis
20: 1899-1903
[Abstract]
[Full Text]
-
Chen, A., Wu, K., Fuchs, S. Y., Tan, P., Gomez, C., Pan, Z.-Q.
(2000). The Conserved RING-H2 Finger of ROC1 Is Required for Ubiquitin Ligation. J. Biol. Chem.
275: 15432-15439
[Abstract]
[Full Text]