Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.5.1.18 (glutathione S-transferase)
 22,582 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

G4 and p13(II) are accessory proteins encoded by the X region of bovine leukemia virus and human T-cell leukemia virus type 1 (HTLV-1), respectively. Disruption of the G4 and p13(II) open reading frames interferes with viral spread in animal model systems, indicating that the corresponding proteins play a key role in viral replication. In addition, G4 is oncogenic in primary cell cultures and is absolutely required for efficient onset of leukemogenesis in sheep. To gain insight into the function of these proteins, we utilized the yeast two-hybrid system to identify protein partners of G4. Results revealed that G4 interacts with farnesyl pyrophosphate synthetase (FPPS), a protein involved in the mevalonate/squalene pathway and in synthesis of FPP, a substrate required for prenylation of Ras. The specificity of the interaction was verified by glutathione S-transferase (GST) pull-down assays and by coimmunoprecipitation experiments. Furthermore, confocal microscopy showed that the subcellular localization of G4 was profoundly affected by FPPS. The G4 protein itself was not prenylated, at least in rabbit reticulocyte lysate-based assays. The domain of G4 required for binding to FPPS was restricted to an amphipathic alpha-helix rich in arginine residues. Subtle mutation of this alpha-helix abrogated G4 oncogenic potential in vitro, providing a biological relevance for FPPS-G4 complex formation in cells. Finally, HTLV-1 p13(II) was also found to specifically interact with FPPS (in yeast as well as in GST pull-down assays) and to colocalize with G4 in mitochondria, suggesting a functional analogy between these oncoviral accessory proteins. Identification of FPPS as a molecular partner for p13(II) and G4 accessory proteins opens new prospects for treatment of retrovirus-induced leukemia.
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PMID:Oncoviral bovine leukemia virus G4 and human T-cell leukemia virus type 1 p13(II) accessory proteins interact with farnesyl pyrophosphate synthetase. 1177 14

Bovine leukemia virus (BLV) tax is an essential gene involved in the transcriptional activation of viral expression. Tax is also believed to be implicated in leukemogenesis because of its ability to immortalize primary cells in vitro. To gain insight into the molecular pathways mediating the activities of this important gene, we identified cellular proteins interacting with Tax. By means of a two-hybrid approach, we show that Tax specifically interacts with MSX2, a general repressor of gene expression. GST pull-down experiments and co-immunoprecipitation assays further confirmed binding specificity. Furthermore, the N-terminal residues 1-79 of MSX2 are required for binding, whereas the C-terminal residues 201-267 of MSX2 do not play a critical role. Whereas the oncogenic potential of Tax in primary cells was only slightly affected by overexpression of MSX2, the other function of Tax, namely LTR-dependent transcriptional activation, was inhibited by MSX2 in human HeLa and bovine B-lymphoblastoid (BL3) cell lines. This MSX2 repression function can be counteracted by overexpression of transcription factors CREB2 and RAP74. The Tax/MSX2 interplay thus results in repression of viral transcriptional activation possibly acting as a regulatory feedback loop. Importantly, this viral gene silencing is not strictly associated with a concomitant loss of Tax oncogenicity as measured by its ability to immortalize primary cells. And interestingly, MSX2 also interacts with and inhibits the transactivation function of the related Tax1 protein encoded by the Human T-cell leukemia virus type 1 (HTLV-1).
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PMID:The homeobox protein MSX2 interacts with tax oncoproteins and represses their transactivation activity. 1597 May 89

Bovine leukemia virus (BLV) is a retrovirus that causes enzootic bovine leucosis. Here, we designed a p24 enzyme-linked immunosorbent assay (ELISA) to detect antibodies specific for BLV capsid protein p24 (encoded by the gag gene) in bovine serum samples. The p24 gene was inserted into an Escherichia coli expression system, and recombinant proteins (GST-p24, p24, and His-p24) were purified. His-p24 was the most suitable antigen for using in the ELISA. The cut-off point was calculated from a receiver operating characteristic curve derived from a set of 582 field samples that previously tested positive or negative by BLV-CoCoMo-qPCR-2, which detects BLV provirus. The new p24 ELISA showed almost the same specificity and sensitivity as a commercial gp51 ELISA kit when used to test field serum samples, and allowed monitoring of p24 antibodies in raw milk and whey. Comparing the results for the p24 ELISA and gp51 ELISA revealed that p24 antibodies were detected earlier than gp51 antibodies in three out of eight calves experimentally infected with BLV, indicating improved detection without diminishing BLV serodiagnosis. Thus, the p24 ELISA is a robust and reliable assay for detecting BLV antibodies in serum or milk, making it is a useful tool for large-scale BLV screening.
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PMID:Development of a new recombinant p24 ELISA system for diagnosis of bovine leukemia virus in serum and milk. 3031 Oct 76