Structure of the human genomic glutathione S-transferase-π gene

Morrow, Charles S.; Cowan, Kenneth H.; Goldsmith, Merrill E.

doi:10.1016/0378-1119(89)90377-6

Cited by 87 publications

(43 citation statements)

References 19 publications

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“…The GSTP1 gene is approximately 4 kb in length, comprises 7 exons and 6 introns (Morrow et al, 1989;Cowell et al, 1988) and codes for a 715 base mRNA ( Figure 1a). The promoter of GSTP1 is located within a 1.5 kb CpG island that also spans exons 1 ± 3 ( Figure 1b).…”

Section: Resultsmentioning

confidence: 99%

Detailed methylation analysis of the glutathione S-transferase π (GSTP1) gene in prostate cancer

et al. 1999

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Glutathione-S-Transferases (GSTs) comprise a family of isoenzymes that provide protection to mammalian cells against electrophilic metabolites of carcinogens and reactive oxygen species. Previous studies have shown that the CpG-rich promoter region of the p-class gene GSTP1 is methylated at single restriction sites in the majority of prostate cancers. In order to understand the nature of abnormal methylation of the GSTP1 gene in prostate cancer we undertook a detailed analysis of methylation at 131 CpG sites spanning the promoter and body of the gene. Our results show that DNA methylation is not con®ned to speci®c CpG sites in the promoter region of the GSTP1 gene but is extensive throughout the CpG island in prostate cancer cells. Furthermore we found that both alleles are abnormally methylated in this region. In normal prostate tissue, the entire CpG island was unmethylated, but extensive methylation was found outside the island in the body of the gene. Loss of GSTP1 expression correlated with DNA methylation of the CpG island in both prostate cancer cell lines and cancer tissues whereas methylation outside the CpG island in normal prostate tissue appeared to have no e ect on gene expression.

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Section: Resultsmentioning

confidence: 99%

Detailed methylation analysis of the glutathione S-transferase π (GSTP1) gene in prostate cancer

et al. 1999

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“…Despite these findings, the complete GST Pi cDNA and gene isolated by different laboratories (23)(24)(25)(26) have been identical, both in nucleotide sequence and in the sequence of the encoded peptide. This study describes for the first time the isolation and characterization of three different full-length GST Pi cDNA variants corresponding to mRNAs of GST Pi genes expressed in human cells and tissues and provides conclusive molecular evidence for polymorphism of the human GST Pi gene locus.…”

Section: Discussionmentioning

confidence: 98%

“…To date, the nucleotide sequences of the complete human GST Pi cDNA and GST Pi gene reported from different laboratories (23)(24)(25)(26) have been identical, leading to the notion that only one human GST Pi gene exists (5). The isolation of two different GST Pi proteins from human placenta (27), however, strongly indicates that genetic polymorphism may exist in the human GST Pi gene locus.…”

mentioning

confidence: 99%

Molecular Cloning, Characterization, and Expression in Escherichia coli of Full-length cDNAs of Three Human Glutathione S-Transferase Pi Gene Variants

Ali‐Osman

Akande

Antoun

et al. 1997

Journal of Biological Chemistry

624

450

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We report the isolation of three full-length cDNAs corresponding to the mRNAs of closely related glutathione S-transferase (GST) Pi genes, designated hGSTP1*A, hGSTP1*B, and hGSTP1*C, expressed in normal cells and malignant gliomas. The variant cDNAs result from A 3 G and C 3 T transitions at nucleotides ؉313 and ؉341, respectively. The transitions changed codon 104 from ATC (Ile) in hGSTP1*A to GTC (Val) in hGSTP1*B and hGSTP1*C and changed codon 113 from GCG (Ala) to GTG (Val) in hGSTP1*C. Both amino changes are in the electrophile-binding active site of the GST Pi peptide. Computer modeling of the deduced crystal structures of the encoded peptides showed significant deviations in the interatomic distances of critical electrophile-binding active site amino acids as a consequence of the amino acid changes. The encoded proteins expressed in Escherichia coli and purified by GSH affinity chromatography showed a 3-fold lower K m (CDNB) and a 3-4-fold higher K cat /K m for the hGSTP1*A encoded protein than the proteins encoded by hGSTP1*B and hGSTP1*C. Analysis of 75 cases showed the relative frequency of hGSTP1*C to be 4-fold higher in malignant gliomas than in normal tissues. These data provide conclusive molecular evidence of allelopolymorphism of the human GST Pi gene locus, resulting in active, functionally different GST Pi proteins, and should facilitate studies of the role of this gene in xenobiotic metabolism, cancer, and other human diseases.

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“…The subunits of mammalian GSTs fall into three classes, Alpha, Mu and Pi, according to their primary structures (Mannervik et al, 1985;Pickett, 1987), and their gene structure is conserved between rat (Telakowski-Hopkins et al, 1986) and mouse (Daniel et al, 1987) for Alpha class genes and between rat (Okuda et al, 1987) and human (Cowell et al, 1988;Morrow et al, 1989) for the Pi class genes. For Mu class genes, three rat sequences have been compared and gene conversion (i.e.…”

Section: Introductionmentioning

confidence: 99%

Structure of human glutathione S-transferase class Mu genes

Taylor¹,

Oliver²,

Sherrington³

et al. 1991

Biochemical Journal

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Nucleotide sequencing of a human cosmid clone shows that the exon-intron structures of a glutathione S-transferase multigene family are conserved between man and rat, that the human gene family is clustered and that gene conversion events have occurred within the cluster. In addition, between man and rat, there is a high degree of nucleotide sequence identity not only in exons but also in some introns. These conserved sequences are coincident with homologous sequences subject to gene conversion in both species, and hence the utilization of gene conversion by this gene family has itself been conserved. By using transient-expression assay the conserved/converted regions are shown to be capable of modulating transcriptional activity. The data suggest that DNA repair by gene conversion may be a chemical immunity mechanism. which could result in acquired resistance to toxins and, in particular, drug resistance due to glutathione S-transferase in tumours.

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Structure of the human genomic glutathione S-transferase-π gene

Cited by 87 publications

References 19 publications

Detailed methylation analysis of the glutathione S-transferase π (GSTP1) gene in prostate cancer

Detailed methylation analysis of the glutathione S-transferase π (GSTP1) gene in prostate cancer

Molecular Cloning, Characterization, and Expression in Escherichia coli of Full-length cDNAs of Three Human Glutathione S-Transferase Pi Gene Variants

Structure of human glutathione S-transferase class Mu genes

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