The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

GSTP1  -  glutathione S-transferase pi 1

Homo sapiens

Synonyms: DFN7, FAEES3, GST class-pi, GST3, GSTP, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of GSTP1

  • For GSTP1, the data were suggestive of a trend of increasing risk with higher numbers of codon 105 valine alleles (compared with isoleucine alleles); a 1.97-fold increased risk of breast cancer (95% CI = 0.77-5.02) was associated with valine/valine homozygosity [1].
  • CONCLUSIONS: The GSTP1 Ile(105)Val polymorphism is associated in a dose-dependent fashion with increased survival of patients with advanced colorectal cancer receiving 5-FU/oxaliplatin chemotherapy [2].
  • Occurrence of the polymorphic GSTP1b variant in the GSTP1 gene resulted in a significantly lower GST enzyme activity (P < 0.05), and GSTP1b was found significantly more often in patients with Barrett's epithelium (70%; P < 0.001) and patients with esophageal adenocarcinoma (76%; P = 0.005), as compared to healthy blood donors (41%) [3].
  • CONCLUSIONS: Our data suggest that the evaluation of DNA hypermethylation at three gene loci (i.e., GSTP1, APC, and PTGS2) is of diagnostic and prognostic value in prostate cancer [4].
  • CONCLUSION: The presence of the GSTP1 variant allele (Val) is associated with a poorer prognosis of esophageal cancer [5].

Psychiatry related information on GSTP1


High impact information on GSTP1

  • Here we show that glutathione S-transferase P1-1 (GSTP1) interacts with FANCC, and that overexpression of both proteins in a myeloid progenitor cell line prevents apoptosis following factor deprivation [8].
  • Although FANCC lacks homology with conventional disulfide reductases, it functions by preventing the formation of inactivating disulfide bonds within GSTP1 during apoptosis [8].
  • GSTP1 is an enzyme that catalyzes the detoxification of xenobiotics and by-products of oxidative stress, and it is frequently upregulated in neoplastic cells [8].
  • From the translational standpoint, we should make an effort to validate the use of some hypermethylated genes as biomarkers of the disease; for example, it may occur with MGMT and GSTP1 in brain and prostate tumors, respectively [9].
  • In a retrospective study, we investigated associations between common polymorphisms in genes for several GST subclasses (GSTP1, GSTT1, GSTM1) and survival of patients with metastatic colorectal cancer receiving 5-fluorouracil (5-FU)/oxaliplatin chemotherapy [2].

Chemical compound and disease context of GSTP1


Biological context of GSTP1


Anatomical context of GSTP1

  • Our study assessed roles of these 3 factors in a human drug-sensitive carcinoma cell line (HEp2), a subclone made resistant by prolonged incubation in doxorubicin (HEp2A), and HEp2 cells stably transfected with human GSTP1 [19].
  • Our results thus suggest that GSTP1 and GSTT1 gene polymorphisms modulate susceptibility to smoking-related cancers of the oral cavity and pharynx [20].
  • Of these, butyrate induces GSTP1 protein expression and GST activity in the human colon tumor cell line HT29 [21].
  • Mucinous tumours significantly overexpressed both TYMS and GSTP1 relative to nonmucinous tumours and patient-matched normal mucosa [22].
  • In conclusion, CYP1A1, GSTM1, and GSTP1 genotyping seems to be a risk predictor of BPDE-DNA adduct formation in leukocytes [23].

Associations of GSTP1 with chemical compounds

  • GSTP1, encoding the pi-class glutathione S-transferase, is commonly inactivated by somatic CpGisland hypermethylation in cancers of the prostate, liver, and breast [16].
  • Identification and characterization of a Pi isoform of glutathione S-transferase (GSTP1) as a zeaxanthin-binding protein in the macula of the human eye [24].
  • Unlike normal or hyperplastic epithelium, GSTP1 CpG island hypermethylation can be detected in some PIA lesions [10].
  • Treatment of Hep3B cells with 5-azadeoxycytidine (5-aza-dC), a methyltransferase inhibitor, activated GSTP1 expression, whereas treatment with trichostatin A, a histone deacetylase inhibitor, had little effect [17].
  • (3R,3'S-meso)-Zeaxanthin, an optically inactive nondietary xanthophyll carotenoid present in the human macula, exhibited a strong induced CD spectrum in association with human macular XBP that was nearly identical to the CD spectrum induced by GSTP1 [24].

Physical interactions of GSTP1

  • FANCC has been shown to interact with several cytoplasmic and nuclear proteins and to delay the onset of apoptosis through redox regulation of GSTP1 [25].
  • Fully methylated but not unmethylated GSTP1 promoter fragment was shown to bind to a complex similar to methyl cytosine-binding protein complex 1 that contains methyl-CpG-binding domain 2 protein (MBD2) in electrophoretic mobility shift assays using LNCaP cell nuclear extracts [26].
  • These results were associated to both a reduction of GATA-1 binding activity to the GSTP1 promoter and to a posttranscriptional destabilization of GSTP1 mRNA in a concentration dependent manner [27].
  • The two zeaxanthin diastereomers displayed synergistic antioxidant effects against both azo lipid peroxyl radical generators when bound to GSTP1 [28].

Regulatory relationships of GSTP1

  • The prostate has potential for GSTP1-dependent detoxification of ATP-activated N-hydroxy-PhIP but little potential for detoxification of N-acetoxy-PhIP by GSTA1 [29].
  • Therefore normal and malignant human cells contain GSTP1 monomers with post-translational modifications, and it is likely that GSTP1 monomers regulate JNK activity in human cells in the same manner as in rodent cells [30].
  • Our data strongly indicate that methylation status of the promoter contributes significantly to the levels of GSTP1 expressed in ER- and ER+ breast cancer cell lines [31].
  • Expression of hGSTP1 largely blocked B[a]P toxicity induced via the moderate activation by rat or human CYP1A1 [32].
  • Relative to control cells, GSTM1-1 was found to inhibit DNA adduct formation of (+)-anti-BPDE most effectively followed by GSTP1-1 and GSTA1-1 (12-, 4-, and 3-fold, respectively) [33].

Other interactions of GSTP1

  • GSTA1/A2 and GSTP1 were found to be the most abundant GSTs in human lung, being present in the bronchial and bronchiolar epithelium of all individuals studied [34].
  • There was also a higher risk of RCC for subjects with the CYP1A1 (m) variant genotype combined with any of the following genotypes: GSTT1 (+) "active" [odds ratio (OR), 2.3; 95% CI, 1.2-4.5], GSTP1 (m) variant (OR, 2.4; 95% CI, 1.0-5.4), or NAT2 (-) "slow acetylator" (OR, 2.5; 95% CI, 1.1-5.5) [35].
  • In multivariate analyses, gender, tobacco smoke exposure, and other factors were associated with the level of expression of CYP1B1, GSTP1, and other transcripts on a gene-specific basis, but substantial interindividual variability in mRNA expression remained unexplained [36].
  • Methyl-CpG-binding domain protein-2 mediates transcriptional repression associated with hypermethylated GSTP1 CpG islands in MCF-7 breast cancer cells [16].
  • There was a significant correlation between methylation and expressional decrease or loss of p16, E-cadherin, and GSTP1 proteins (P = 0.028, P = 0.044, and P < 0.001, respectively) [37].

Analytical, diagnostic and therapeutic context of GSTP1

  • Immunocytochemistry with an antibody to GSTP1 on human macula sections showed highest labeling in the outer and inner plexiform layers [24].
  • In the clone that expressed GSTP1 mRNA determined by Northern blot analysis and quantitative reverse transcriptase (RT)-PCR, widespread demethylation of at least one GSTP1 allele was evident [17].
  • Chromatin immunoprecipitation experiments revealed the presence of MBD2, but not Sp1, at the GSTP1 promoter in Hep3B cells [17].
  • Although quantitative methylation-specific PCR (QMSP) of the GSTP1 promoter has demonstrated near perfect specificity for cancer detection in prostate biopsies, we postulated that identification and characterization of additional methylation markers might further improve its high (80-90%) sensitivity [38].
  • We assessed the association of GSTP1 genetic polymorphisms and the susceptibility to childhood acute lymphoblastic leukaemia (ALL) by conducting a case-control study on 278 ALL patients and 303 healthy controls, both of French-Canadian origin [39].


  1. Association between glutathione S-transferase M1, P1, and T1 genetic polymorphisms and development of breast cancer. Helzlsouer, K.J., Selmin, O., Huang, H.Y., Strickland, P.T., Hoffman, S., Alberg, A.J., Watson, M., Comstock, G.W., Bell, D. J. Natl. Cancer Inst. (1998) [Pubmed]
  2. Association between glutathione S-transferase P1, T1, and M1 genetic polymorphism and survival of patients with metastatic colorectal cancer. Stoehlmacher, J., Park, D.J., Zhang, W., Groshen, S., Tsao-Wei, D.D., Yu, M.C., Lenz, H.J. J. Natl. Cancer Inst. (2002) [Pubmed]
  3. Polymorphic expression of the glutathione S-transferase P1 gene and its susceptibility to Barrett's esophagus and esophageal carcinoma. van Lieshout, E.M., Roelofs, H.M., Dekker, S., Mulder, C.J., Wobbes, T., Jansen, J.B., Peters, W.H. Cancer Res. (1999) [Pubmed]
  4. Diagnostic and prognostic information in prostate cancer with the help of a small set of hypermethylated gene loci. Bastian, P.J., Ellinger, J., Wellmann, A., Wernert, N., Heukamp, L.C., Müller, S.C., von Ruecker, A. Clin. Cancer Res. (2005) [Pubmed]
  5. Association of GSTP1 polymorphism and survival for esophageal cancer. Lee, J.M., Wu, M.T., Lee, Y.C., Yang, S.Y., Chen, J.S., Hsu, H.H., Huang, P.M., Kuo, S.W., Lee, C.J., Chen, C.J. Clin. Cancer Res. (2005) [Pubmed]
  6. Possible genetic damage in the Czech nuclear power plant workers. Sram, R.J., Rössner, P., Rubes, J., Beskid, O., Dusek, Z., Chvatalova, I., Schmuczerova, J., Milcova, A., Solansky, I., Bavorova, H., Ocadlikova, D., Kopecna, O., Musilova, P. Mutat. Res. (2006) [Pubmed]
  7. The glutathione S-transferase polymorphisms in a control population and in Alzheimer's disease patients. Zuntar, I., Kalanj-Bognar, S., Topić, E., Petlevski, R., Stefanović, M., Demarin, V. Clin. Chem. Lab. Med. (2004) [Pubmed]
  8. Fanconi anemia group C protein prevents apoptosis in hematopoietic cells through redox regulation of GSTP1. Cumming, R.C., Lightfoot, J., Beard, K., Youssoufian, H., O'Brien, P.J., Buchwald, M. Nat. Med. (2001) [Pubmed]
  9. Aberrant DNA methylation as a cancer-inducing mechanism. Esteller, M. Annu. Rev. Pharmacol. Toxicol. (2005) [Pubmed]
  10. Hypermethylation of the human glutathione S-transferase-pi gene (GSTP1) CpG island is present in a subset of proliferative inflammatory atrophy lesions but not in normal or hyperplastic epithelium of the prostate: a detailed study using laser-capture microdissection. Nakayama, M., Bennett, C.J., Hicks, J.L., Epstein, J.I., Platz, E.A., Nelson, W.G., De Marzo, A.M. Am. J. Pathol. (2003) [Pubmed]
  11. Glutathione S-transferase M3 (A/A) genotype as a risk factor for oral cancer and leukoplakia among Indian tobacco smokers. Sikdar, N., Paul, R.R., Roy, B. Int. J. Cancer (2004) [Pubmed]
  12. Glutathione-S-transferase P1 gene polymorphism and susceptibility to endometriosis. Ertunc, D., Aban, M., Tok, E.C., Tamer, L., Arslan, M., Dilek, S. Hum. Reprod. (2005) [Pubmed]
  13. Polymorphisms of N-acetyltransferases, glutathione S-transferases, microsomal epoxide hydrolase and sulfotransferases: influence on cancer susceptibility. Hengstler, J.G., Arand, M., Herrero, M.E., Oesch, F. Recent Results Cancer Res. (1998) [Pubmed]
  14. Prognostic value of p53, glutathione S-transferase pi, and thymidylate synthase for neoadjuvant cisplatin-based chemotherapy in head and neck cancer. Shiga, H., Heath, E.I., Rasmussen, A.A., Trock, B., Johnston, P.G., Forastiere, A.A., Langmacher, M., Baylor, A., Lee, M., Cullen, K.J. Clin. Cancer Res. (1999) [Pubmed]
  15. Genetic polymorphisms of biotransformation enzymes in patients with Hodgkin's and non-Hodgkin's lymphomas. Sarmanová, J., Benesová, K., Gut, I., Nedelcheva-Kristensen, V., Tynková, L., Soucek, P. Hum. Mol. Genet. (2001) [Pubmed]
  16. Methyl-CpG-binding domain protein-2 mediates transcriptional repression associated with hypermethylated GSTP1 CpG islands in MCF-7 breast cancer cells. Lin, X., Nelson, W.G. Cancer Res. (2003) [Pubmed]
  17. Methyl-CpG binding domain protein 2 represses transcription from hypermethylated pi-class glutathione S-transferase gene promoters in hepatocellular carcinoma cells. Bakker, J., Lin, X., Nelson, W.G. J. Biol. Chem. (2002) [Pubmed]
  18. High gene expression of TS1, GSTP1, and ERCC1 are risk factors for survival in patients treated with trimodality therapy for esophageal cancer. Joshi, M.B., Shirota, Y., Danenberg, K.D., Conlon, D.H., Salonga, D.S., Herndon, J.E., Danenberg, P.V., Harpole, D.H. Clin. Cancer Res. (2005) [Pubmed]
  19. Role of glutathione S-transferase P1, P-glycoprotein and multidrug resistance-associated protein 1 in acquired doxorubicin resistance. Harbottle, A., Daly, A.K., Atherton, K., Campbell, F.C. Int. J. Cancer (2001) [Pubmed]
  20. Glutathione S-transferase GSTM1, GSTM3, GSTP1 and GSTT1 genotypes and the risk of smoking-related oral and pharyngeal cancers. Jourenkova-Mironova, N., Voho, A., Bouchardy, C., Wikman, H., Dayer, P., Benhamou, S., Hirvonen, A. Int. J. Cancer (1999) [Pubmed]
  21. Expression of glutathione S-transferases (GSTs) in human colon cells and inducibility of GSTM2 by butyrate. Ebert, M.N., Klinder, A., Peters, W.H., Schäferhenrich, A., Sendt, W., Scheele, J., Pool-Zobel, B.L. Carcinogenesis (2003) [Pubmed]
  22. Unfavourable expression of pharmacologic markers in mucinous colorectal cancer. Glasgow, S.C., Yu, J., Carvalho, L.P., Shannon, W.D., Fleshman, J.W., McLeod, H.L. Br. J. Cancer (2005) [Pubmed]
  23. Benzo(a)pyrene diolepoxide (BPDE)-DNA adduct levels in leukocytes of smokers in relation to polymorphism of CYP1A1, GSTM1, GSTP1, GSTT1, and mEH. Lodovici, M., Luceri, C., Guglielmi, F., Bacci, C., Akpan, V., Fonnesu, M.L., Boddi, V., Dolara, P. Cancer Epidemiol. Biomarkers Prev. (2004) [Pubmed]
  24. Identification and characterization of a Pi isoform of glutathione S-transferase (GSTP1) as a zeaxanthin-binding protein in the macula of the human eye. Bhosale, P., Larson, A.J., Frederick, J.M., Southwick, K., Thulin, C.D., Bernstein, P.S. J. Biol. Chem. (2004) [Pubmed]
  25. Regulation of the Fanconi anemia group C protein through proteolytic modification. Brodeur, I., Goulet, I., Tremblay, C.S., Charbonneau, C., Delisle, M.C., Godin, C., Huard, C., Khandjian, E.W., Buchwald, M., Lévesque, G., Carreau, M. J. Biol. Chem. (2004) [Pubmed]
  26. Cytosine methylation represses glutathione S-transferase P1 (GSTP1) gene expression in human prostate cancer cells. Singal, R., van Wert, J., Bashambu, M. Cancer Res. (2001) [Pubmed]
  27. Transcriptional and post-transcriptional regulation of glutathione S-transferase P1 expression during butyric acid-induced differentiation of K562 cells. Schnekenburger, M., Morceau, F., Henry, E., Blasius, R., Dicato, M., Trentesaux, C., Diederich, M. Leuk. Res. (2006) [Pubmed]
  28. Synergistic effects of zeaxanthin and its binding protein in the prevention of lipid membrane oxidation. Bhosale, P., Bernstein, P.S. Biochim. Biophys. Acta (2005) [Pubmed]
  29. Expression of cytochromes P450 and glutathione S-transferases in human prostate, and the potential for activation of heterocyclic amine carcinogens via acetyl-coA-, PAPS- and ATP-dependent pathways. Di Paolo, O.A., Teitel, C.H., Nowell, S., Coles, B.F., Kadlubar, F.F. Int. J. Cancer (2005) [Pubmed]
  30. Characterization of the molecular forms of glutathione S-transferase P1 in human gastric cancer cells (Kato III) and in normal human erythrocytes. Ranganathan, P.N., Whalen, R., Boyer, T.D. Biochem. J. (2005) [Pubmed]
  31. Methylation-mediated regulation of the glutathione S-transferase P1 gene in human breast cancer cells. Jhaveri, M.S., Morrow, C.S. Gene (1998) [Pubmed]
  32. Modeling the metabolic competency of glutathione S-transferases using genetically modified cell lines. Townsend, A.J., Kabler, S.L., Doehmer, J., Morrow, C.S. Toxicology (2002) [Pubmed]
  33. Glutathione conjugation and DNA adduct formation of dibenzo[a,l]pyrene and benzo[a]pyrene diol epoxides in V79 cells stably expressing different human glutathione transferases. Sundberg, K., Dreij, K., Seidel, A., Jernström, B. Chem. Res. Toxicol. (2002) [Pubmed]
  34. Immunohistochemical localization of glutathione S-transferases in human lung. Anttila, S., Hirvonen, A., Vainio, H., Husgafvel-Pursiainen, K., Hayes, J.D., Ketterer, B. Cancer Res. (1993) [Pubmed]
  35. Candidate genetic modifiers of individual susceptibility to renal cell carcinoma: a study of polymorphic human xenobiotic-metabolizing enzymes. Longuemaux, S., Deloménie, C., Gallou, C., Méjean, A., Vincent-Viry, M., Bouvier, R., Droz, D., Krishnamoorthy, R., Galteau, M.M., Junien, C., Béroud, C., Dupret, J.M. Cancer Res. (1999) [Pubmed]
  36. Gene-environment interaction signatures by quantitative mRNA profiling in exfoliated buccal mucosal cells. Spivack, S.D., Hurteau, G.J., Jain, R., Kumar, S.V., Aldous, K.M., Gierthy, J.F., Kaminsky, L.S. Cancer Res. (2004) [Pubmed]
  37. Aberrant CpG island methylation of multiple genes in intrahepatic cholangiocarcinoma. Lee, S., Kim, W.H., Jung, H.Y., Yang, M.H., Kang, G.H. Am. J. Pathol. (2002) [Pubmed]
  38. A quantitative promoter methylation profile of prostate cancer. Jerónimo, C., Henrique, R., Hoque, M.O., Mambo, E., Ribeiro, F.R., Varzim, G., Oliveira, J., Teixeira, M.R., Lopes, C., Sidransky, D. Clin. Cancer Res. (2004) [Pubmed]
  39. Glutathione S-transferase P1 genetic polymorphisms and susceptibility to childhood acute lymphoblastic leukaemia. Krajinovic, M., Labuda, D., Sinnett, D. Pharmacogenetics (2002) [Pubmed]
WikiGenes - Universities