Details of Host Protein-DME Interaction (HOSPPI)

General Information of Drug-Metabolizing Enzyme (DME ID: DME0088)
DME Name	Glutathione S-transferase pi (GSTP1), Homo sapiens	DME Info
UniProt ID	GSTP1_HUMAN
EC Number	EC: 2.5.1.18 (Click to Show/Hide the Complete EC Tree) Transferase Alkyl/aryl transferase Alkyl/aryl transferase EC: 2.5.1.18
Lineage	Species: Homo sapiens (Click to Show/Hide the Complete Species Lineage) Kingdom: Metazoa Phylum: Chordata Class: Mammalia Order: Primates Family: Hominidae Genus: Homo Species: Homo sapiens
Interactome

Disease Specific Interactions between Host Protein and DME (HOSPPI)
ICD Disease Classification Healthy
ICD-11: Healthy		Click to Show/Hide the Full List of HOSPPI: 1 HOSPPI
Oligomerization
GS-transferase P (GSTP1)		Health		Homodimer
Uniprot ID	GSTP1_HUMAN
Interaction Name	GSTP1-GSTP1 homodimerization				[1]
Studied Cell Lines	Jurkat cells
Description	Glutathione S-transferase Pi (GSTP1) is reported as a homodimer, which leads to an altered activity of the drug-metabolizing enzyme Glutathione S-transferase pi. As a result, the GSTP1 homodimerization can modulate the drug-metabolizing process of Glutathione S-transferase pi.
ICD Disease Classification 02 Neoplasms
ICD-11: 2A00 Brain cancer		Click to Show/Hide the Full List of HOSPPI: 2 HOSPPI
Transcription-factor regulation
Tumor suppressor p53 (TP53)		Glioblastoma		Activation
Uniprot ID	P53_HUMAN
Interaction Name	TP53-GSTP1 interaction				[2]
Studied Cell Lines	MGR2, MGR3, UW28, UW281, UW78 cell lines
Ensembl ID	ENSG00000141510
Description	Tumor suppressor p53 (TP53) is reported to activate the transcription of GSTP1 gene, which leads to an increased expression of the drug-metabolizing enzyme Glutathione S-transferase pi. As a result, the interaction between TP53 and GSTP1 can activate the drug-metabolizing process of Glutathione S-transferase pi.
Tumor suppressor p53 (TP53)		Medulloblastoma		Activation
Uniprot ID	P53_HUMAN
Interaction Name	TP53-GSTP1 interaction				[2]
Studied Cell Lines	UW228 cell line
Ensembl ID	ENSG00000141510
Description	Tumor suppressor p53 (TP53) is reported to activate the transcription of GSTP1 gene, which leads to an increased expression of the drug-metabolizing enzyme Glutathione S-transferase pi. As a result, the interaction between TP53 and GSTP1 can activate the drug-metabolizing process of Glutathione S-transferase pi.
ICD-11: 2B33 Acute lymphoblastic leukemia		Click to Show/Hide the Full List of HOSPPI: 2 HOSPPI
Transcription-factor regulation
Nuclear factor kappa-B p105 (NFKB1)		Acute lymphoblastic leukemia		Activation
Uniprot ID	NFKB1_HUMAN
Interaction Name	NFKB1-GSTP1 interaction				[3]
Studied Cell Lines	K562 cell line
Ensembl ID	ENSG00000109320
Description	Nuclear factor kappa-B p105 (NFKB1) is reported to activate the transcription of GSTP1 gene, which leads to an increased expression of the drug-metabolizing enzyme Glutathione S-transferase pi. As a result, the interaction between NFKB1 and GSTP1 can activate the drug-metabolizing process of Glutathione S-transferase pi.
Transcription factor p65 (RELA)		Acute lymphoblastic leukemia		Activation
Uniprot ID	TF65_HUMAN
Interaction Name	RELA-GSTP1 interaction				[3]
Studied Cell Lines	K562 cell line
Ensembl ID	ENSG00000173039
Description	Transcription factor p65 (RELA) is reported to activate the transcription of GSTP1 gene, which leads to an increased expression of the drug-metabolizing enzyme Glutathione S-transferase pi. As a result, the interaction between RELA and GSTP1 can activate the drug-metabolizing process of Glutathione S-transferase pi.
ICD-11: 2B58 Leiomyosarcoma		Click to Show/Hide the Full List of HOSPPI: 1 HOSPPI
Transcription-factor regulation
Tumor suppressor p53 (TP53)		Leiomyosarcoma		Activation
Uniprot ID	P53_HUMAN
Interaction Name	TP53-GSTP1 interaction				[2]
Studied Cell Lines	SKLMS-1 cell line
Ensembl ID	ENSG00000141510
Description	Tumor suppressor p53 (TP53) is reported to activate the transcription of GSTP1 gene, which leads to an increased expression of the drug-metabolizing enzyme Glutathione S-transferase pi. As a result, the interaction between TP53 and GSTP1 can activate the drug-metabolizing process of Glutathione S-transferase pi.
ICD-11: 2C12 Liver cancer		Click to Show/Hide the Full List of HOSPPI: 3 HOSPPI
Transcription-factor regulation
Demethylase (MBD2)		Liver cancer		Repression
Uniprot ID	MBD2_HUMAN
Interaction Name	MBD2-GSTP1 interaction				[4], [5], [6]
Studied Cell Lines	Hep3B cell line
Ensembl ID	ENSG00000134046
Description	Demethylase (MBD2) is reported to repress the transcription of GSTP1 gene, which leads to a decreased expression of the drug-metabolizing enzyme Glutathione S-transferase pi. As a result, the interaction between MBD2 and GSTP1 can repress the drug-metabolizing process of Glutathione S-transferase pi.
Histone modification
Histone deacetylases (HDACs)		Liver cancer		Repression
Uniprot ID	HDAC1_HUMAN
Interaction Name	HDACs-GSTP1 interaction				[7]
Studied Cell Lines	hepatocellular LCL-PI 11 cell line
Description	Histone deacetylases (HDACs) are reported to deacetylate the GSTP1 gene and thereby repress the transcriptional activity of the drug-metabolizing enzyme Glutathione S-transferase pi. As a result, the interaction between HDACs and GSTP1 can inhibit the drug-metabolizing process of Glutathione S-transferase pi.
DNA methylation
DNA methyltransferase (DNMT)		Liver cancer		Moderate hypermethylation
Interaction Name	DNMT-GSTP1 interaction
The Methylation Level of Disease Section Compare with the Healthy Individual Tissue	Moderate hypermethylation p-value: 4.88E-19; delta-beta: 2.32E-01
Description	DNA methyltransferase (DNMT) is reported to moderatly hyper-methylate the GSTP1 gene, which leads to a moderatly decreased expression of the drug-metabolizing enzyme Glutathione S-transferase pi. As a result, the interaction between DNMT and GSTP1 can moderatly affect the drug-metabolizing process of Glutathione S-transferase pi.
DME methylation in the diseased tissue of patients DME methylation in the normal tissue adjacent to the diseased tissue of patients DME methylation in the normal tissue of healthy individuals DME methylation in tissue other than the diseased tissue of patients
Violin Diagram of DME Disease-specific Methylation Level			Click to View the Clearer Original Diagram
Download DME methylation barchart for all samples Download DME methylation data of patients in the disease section of the tissue Download DME methylation data of patients in the normal section of the tissue adjacent to the disease section Download DME methylation data in the tissue of healthy individual Download DME methylation data in the tissue of the other disease section
ICD-11: 2C25 Lung cancer		Click to Show/Hide the Full List of HOSPPI: 1 HOSPPI
Non-coding RNA regulation
hsa-miR-513a-3p		Lung cancer		Suppression
miRBase ID	MIMAT0004777
Interaction Name	hsa-miR-513a-3p--GSTP1 regulation				[8]
Studied Cell Lines	A549 cell line
Description	hsa-miR-513a-3p is reported to suppress GSTP1 mRNA translation by binding to the 3' untranslated region (3'UTR) of GSTP1 mRNA, which leads to a decreased expression of the drug-metabolizing enzyme Glutathione S-transferase pi.
ICD-11: 2C60 Breast cancer		Click to Show/Hide the Full List of HOSPPI: 2 HOSPPI
Transcription-factor regulation
Transcription factor Sp1 (SP1)		Breast cancer		Activation
Uniprot ID	SP1_HUMAN
Interaction Name	SP1-GSTP1 interaction				[10]
Studied Cell Lines	Human mammary carcinoma cell line (MCF7)
Ensembl ID	ENSG00000185591
Description	Transcription factor Sp1 (SP1) is reported to activate the transcription of GSTP1 gene, which leads to an increased expression of the drug-metabolizing enzyme Glutathione S-transferase pi. As a result, the interaction between SP1 and GSTP1 can activate the drug-metabolizing process of Glutathione S-transferase pi.
Non-coding RNA regulation
hsa-miR-133a-3p		Breast cancer		Suppression
miRBase ID	MIMAT0000427
Interaction Name	hsa-miR-133a-3p--GSTP1 regulation				[9]
Studied Cell Lines	Bladder cancer cells
Description	hsa-miR-133a-3p is reported to suppress GSTP1 mRNA translation by binding to the 3' untranslated region (3'UTR) of GSTP1 mRNA, which leads to a decreased expression of the drug-metabolizing enzyme Glutathione S-transferase pi.
ICD-11: 2C73 Ovarian cancer		Click to Show/Hide the Full List of HOSPPI: 1 HOSPPI
Non-coding RNA regulation
hsa-miR-133b		Ovarian cancer		Suppression
miRBase ID	MIMAT0000770
Interaction Name	hsa-miR-133b--GSTP1 regulation				[11]
Studied Cell Lines	A2780 cell line
Description	hsa-miR-133b is reported to suppress GSTP1 mRNA translation by binding to the 3' untranslated region (3'UTR) of GSTP1 mRNA, which leads to a decreased expression of the drug-metabolizing enzyme Glutathione S-transferase pi.
ICD-11: 2C82 Prostate cancer		Click to Show/Hide the Full List of HOSPPI: 1 HOSPPI
DNA methylation
DNA methyltransferase (DNMT)		Prostate cancer		Significant hypermethylation
Interaction Name	DNMT-GSTP1 interaction
The Methylation Level of Disease Section Compare with the Healthy Individual Tissue	Significant hypermethylation p-value: 7.67E-08; delta-beta: 3.75E-01
Description	DNA methyltransferase (DNMT) is reported to significantly hyper-methylate the GSTP1 gene, which leads to a significantly decreased expression of the drug-metabolizing enzyme Glutathione S-transferase pi. As a result, the interaction between DNMT and GSTP1 can significantly affect the drug-metabolizing process of Glutathione S-transferase pi.
DME methylation in the diseased tissue of patients DME methylation in the normal tissue of healthy individuals
Violin Diagram of DME Disease-specific Methylation Level			Click to View the Clearer Original Diagram
Download DME methylation barchart for all samples Download DME methylation data of patients in the disease section of the tissue Download DME methylation data in the tissue of healthy individual
ICD-11: 2E06 Prostate cancer metastasis		Click to Show/Hide the Full List of HOSPPI: 1 HOSPPI
DNA methylation
DNA methyltransferase (DNMT)		Prostate cancer metastasis		Significant hypermethylation
Interaction Name	DNMT-GSTP1 interaction
The Methylation Level of Disease Section Compare with the Healthy Individual Tissue	Significant hypermethylation p-value: 4.22E-05; delta-beta: 4.62E-01
Description	DNA methyltransferase (DNMT) is reported to significantly hyper-methylate the GSTP1 gene, which leads to a significantly decreased expression of the drug-metabolizing enzyme Glutathione S-transferase pi. As a result, the interaction between DNMT and GSTP1 can significantly affect the drug-metabolizing process of Glutathione S-transferase pi.
DME methylation in the diseased tissue of patients DME methylation in the normal tissue of healthy individuals
Violin Diagram of DME Disease-specific Methylation Level			Click to View the Clearer Original Diagram
Download DME methylation barchart for all samples Download DME methylation data of patients in the disease section of the tissue Download DME methylation data in the tissue of healthy individual

References
1	Modulation of GSTP1-1 oligomerization by electrophilic inflammatory mediators and reactive drugs. Inflamm Allergy Drug Targets. 2013 Jun;12(3):162-71.
2	Identification and functional characterization of the human glutathione S-transferase P1 gene as a novel transcriptional target of the p53 tumor suppressor gene. Mol Cancer Res. 2008 May;6(5):843-50.
3	Regulation of glutathione S-transferase P1-1 gene expression by NF-kappaB in tumor necrosis factor alpha-treated K562 leukemia cells. Biochem Pharmacol. 2004 Apr 1;67(7):1227-38.
4	Methyl-CpG binding domain protein 2 represses transcription from hypermethylated pi-class glutathione S-transferase gene promoters in hepatocellular carcinoma cells. J Biol Chem. 2002 Jun 21;277(25):22573-80.
5	Methyl-CpG-binding domain protein-2 mediates transcriptional repression associated with hypermethylated GSTP1 CpG islands in MCF-7 breast cancer cells. Cancer Res. 2003 Jan 15;63(2):498-504.
6	Promoter demethylation and chromatin remodeling by green tea polyphenols leads to re-expression of GSTP1 in human prostate cancer cells. Int J Cancer. 2010 Jun 1;126(11):2520-33.
7	Glutathione-S-transferase pi 1(GSTP1) gene silencing in prostate cancer cells is reversed by the histone deacetylase inhibitor depsipeptide. Biochem Biophys Res Commun. 2011 Sep 9;412(4):606-11.
8	miR-513a-3p sensitizes human lung adenocarcinoma cells to chemotherapy by targeting GSTP1. Lung Cancer. 2012 Sep;77(3):488-94.
9	MiR-133a induces apoptosis through direct regulation of GSTP1 in bladder cancer cell lines. Urol Oncol. 2013 Jan;31(1):115-23.
10	Sp1-mediated transcriptional activation of the human Pi class glutathione S-transferase promoter. J Biol Chem. 1996 Jan 12;271(2):1054-60.
11	MicroRNA-133b targets glutathione S-transferase pi expression to increase ovarian cancer cell sensitivity to chemotherapy drugs. Drug Des Devel Ther. 2015 Sep 16;9:5225-35.

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