Glutathione S-transferase Mu 4 is an enzyme that in humans is encoded by the GSTM4gene.[1][2]
Cytosolic and membrane-bound forms of glutathione S-transferase are encoded by two distinct supergene families. At present, eight distinct classes of the soluble cytoplasmic mammalian glutathione S-transferases have been identified: alpha, kappa, mu, omega, pi, sigma, theta and zeta. This gene encodes a glutathione S-transferase that belongs to the mu class. The mu class of enzymes functions in the detoxification of electrophilic compounds, including carcinogens, therapeutic drugs, environmental toxins and products of oxidative stress, by conjugation with glutathione. The genes encoding the mu class of enzymes are organized in a gene cluster on chromosome 1p13.3 and are known to be highly polymorphic. These genetic variations can change an individual's susceptibility to carcinogens and toxins as well as affect the toxicity and efficacy of certain drugs. Diversification of these genes has occurred in regions encoding substrate-binding domains, as well as in tissue expression patterns, to accommodate an increasing number of foreign compounds. Multiple transcript variants, each encoding a distinct protein isoform, have been identified.[2]
In the August 2009 issue of Oncogene journal, researchers at Huntsman Cancer Institute (HCI) at the University of Utah demonstrated that expression levels of GSTM4 could predict response to chemotherapy in patients with Ewing's Sarcoma. The study found that patients who did not respond to chemotherapy had high levels of GSTM4.[3]
References
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Comstock KE, Widersten M, Hao XY, et al. (1994). "A comparison of the enzymatic and physicochemical properties of human glutathione transferase M4-4 and three other human Mu class enzymes". Arch. Biochem. Biophys. 311 (2): 487–95. doi:10.1006/abbi.1994.1266. PMID8203914.
Rozell B, Hansson HA, Guthenberg C, et al. (1994). "Glutathione transferases of classes alpha, mu and pi show selective expression in different regions of rat kidney". Xenobiotica. 23 (8): 835–49. doi:10.3109/00498259309059412. PMID8284940.
Comstock KE, Johnson KJ, Rifenbery D, Henner WD (1993). "Isolation and analysis of the gene and cDNA for a human Mu class glutathione S-transferase, GSTM4". J. Biol. Chem. 268 (23): 16958–65. PMID8349586.
Patskovsky YV, Patskovska LN, Listowsky I (2000). "An asparagine-phenylalanine substitution accounts for catalytic differences between hGSTM3-3 and other human class mu glutathione S-transferases". Biochemistry. 38 (49): 16187–94. doi:10.1021/bi991714t. PMID10587441.
Beuckmann CT, Fujimori K, Urade Y, Hayaishi O (2000). "Identification of mu-class glutathione transferases M2-2 and M3-3 as cytosolic prostaglandin E synthases in the human brain". Neurochem. Res. 25 (5): 733–8. doi:10.1023/A:1007579507804. PMID10905636.
Liloglou T, Walters M, Maloney P, et al. (2003). "A T2517C polymorphism in the GSTM4 gene is associated with risk of developing lung cancer". Lung Cancer. 37 (2): 143–6. doi:10.1016/S0169-5002(02)00078-8. PMID12140136.
Stelzl U, Worm U, Lalowski M, et al. (2005). "A human protein-protein interaction network: a resource for annotating the proteome". Cell. 122 (6): 957–68. doi:10.1016/j.cell.2005.08.029. PMID16169070.
Rual JF, Venkatesan K, Hao T, et al. (2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173–8. doi:10.1038/nature04209. PMID16189514.
Denson J, Xi Z, Wu Y, et al. (2006). "Screening for inter-individual splicing differences in human GSTM4 and the discovery of a single nucleotide substitution related to the tandem skipping of two exons". Gene. 379: 148–55. doi:10.1016/j.gene.2006.05.012. PMID16854533.
