Disease relevance of GSTM4

• Complementary DNAs for human GSTM2, GSTM3, and GSTM4 subunits were cloned, and recombinant proteins were expressed as homodimers in Escherichia coli [1].
• One hundred and forty-six individuals with invasive epithelial ovarian cancer were genotyped using a three-primer PCR reaction specific for the GSTM1 gene and an internal control glutathione S-transferase mu-4 (GSTM4) [2].
• This is the first report on the implication of a polymorphism in the GSTM4 gene in lung cancer risk [3].

High impact information on GSTM4

• GSTM4 differs from a partial gene sequence, termed GSTmu2 (Taylor, J. B., Oliver, J., Sherrington, R., and Pemble, S. E. (1991) Biochem. J. 274, 587-593), in exons 3 through 5 by only 11 nucleotides within introns [4].
• Isolation and analysis of the gene and cDNA for a human Mu class glutathione S-transferase, GSTM4 [4].
• The polypeptide encoded by the GSTM4 cDNA, produced in a bacterial expression system, conjugates 1-chloro-2,4-dinitrobenzene to GSH with a specific activity of 1.39 +/- 0.21 mumol/min/mg [4].
• The cDNA for GSTM4 was isolated from a library derived from the cervical carcinoma cell line, HeLa [4].
• Northern blots demonstrate the presence of GSTM4 mRNA in human heart, placenta, lung, brain, liver, skeletal muscle, pancreas, testis, cerebral cortex, uterus, ovary, a lymphoblastoid cell line, and four carcinoma cell lines [4].

Biological context of GSTM4

• In situ hybridization with the GSTM4 probe localized a major region of hybridization on chromosome band 1p13 [5].
• The coding region of the GSTM4 gene, including the seven introns, encompasses 5.0 kb, whereas the same region of GSTM1b is 5.5 kb; the difference in the size of the two genes is due to the length of intron 7 [6].
• Deduced amino acid sequence, gene structure and chromosomal location of a novel human class Mu glutathione S-transferase, GSTM4 [6].
• As a positive control each assay amplified part of GSTM4, a mu class gene which is not polymorphic but which shows strong sequence homology to GSTM1 [7].
• RESULTS: A single microsatellite marker in the GSTM4 gene showed some evidence of linkage, LOD 1.6 (p = 0.006) [8].

Anatomical context of GSTM4

• GSTM4 and GSTM5 subunits, here identified for the first time in human tissue extracts, were minor components, with GSTM5 found only in brain, lung and testis [9].

Associations of GSTM4 with chemical compounds

• The recombinant GSTM2-2 and 3-3 catalyzed the conversion of PGH2 to PGE2 at the rates of 282 and 923 nmol/min/mg of protein, respectively, at the optimal pH of 8, whereas GSTM4-4 was inactive; although all three enzymes showed GST activity [1].
• The cDNA encoding this novel transferase, designated 'GSTM4' has been isolated and the enzyme shown to be comprised of 218 amino acids (including the initiator methionine residue) with an M(r) of approx. 25.5 kDa [6].
• CDNA-derived amino acid sequence analysis revealed that mfaGSTM1 and mfaGSTM2 share 97% and 96% homology with the human mu-class GSTs hGSTM4 and hGSTM2, respectively [10].

Other interactions of GSTM4

• DNA sequencing allowed a GSTM4-gene-specific oligo-primer to be designed which has been utilized in a PCR-based assay to determine that the GSTM4 gene is located on chromosome 1 [6].

Analytical, diagnostic and therapeutic context of GSTM4

• To identify inter-individual differences in the splicing pattern of the GSTM4 gene, we used reverse transcriptase polymerase chain reaction (RT-PCR) to screen cDNA from 96 human liver samples [11].
• Ewing's sarcoma patients who have higher expression of GSTM4 seem to be less responsive to chemotherapy than those who have lower expression of the protein  .

References