Disease relevance of Gsto1

• Murine mammary tumor virus (MuMTV) p28 was detected in all tumors tested, independent of time of tumor appearance or tumor type, although keratinizing cells in adenoacanthomatous tumors did not contribute to MuMTV antigen expression [1].
• In the absence (but not presence) of elevated Bcl-2 levels, apoptotic signaling by adenovirus E1A oncoproteins promote cleavage of p28 at the two caspase recognition sites [2].
• Under conditions of limiting antibody in competitive binding assays, as little as 50 pg of purified p28, as well as disrupted MMTV virions and mammary tumor extracts, competed specifically with 125I-labeled MMTV p28 [3].
• The 28,000-dalton (p28) major structural polypeptide of the mouse mammary tumor virus (MMTV) was isolated and used to develop a highly sensitive and specific radioimmunoassay [3].
• Mouse hepatitis virus strain A59 encodes a papain-like cysteine proteinase (PLP-1) that, during translation of ORF1a, cleaves p28 from the amino terminus of the growing polypeptide chain [4].

High impact information on Gsto1

• Similarly, the presence of C3H MMTV LTR mRNA in mammary glands, as detected by PCR, paralleled p28 levels [5].
• It is a 28-kD (p28) polytopic integral protein of the endoplasmic reticulum whose COOH-terminal cytosolic region contains overlapping predicted leucine zipper and weak death effector homology domains, flanked on either side by identical caspase recognition sites [2].
• Unlike other mammalian GSTs, GSTO 1-1 appears to have an active site cysteine that can form a disulfide bond with glutathione [6].
• Northern analysis of the mRNA of this protein showed abundant expression in mouse heart and liver tissues, whereas anti-p28 antibody binding identified p28 expression in mouse 3T3 cells and early passage mouse embryo fibroblasts [7].
• Based on sequence homology and protein activity we conclude that p28 acts as a small stress response protein, likely involved in cellular redox homeostasis, and belongs to a family of GST-like proteins related to class theta GSTs [7].

Chemical compound and disease context of Gsto1

• Although the reverse transcriptase enzyme is of normal size, the major structural protein of the defective virions has a molecular weight of 28,000 (p28), in contrast to the p30 of M-MuLV, and no viral glycoprotein was evident [8].
• Determinants of the p28 cleavage site recognized by the first papain-like cysteine proteinase of murine coronavirus [9].
• Comparison of two-dimensional maps of tyrosine containing tryptic peptides of p28 demonstrated that three CAEV isolates had similar maps while a fourth CAEV isolate, VV and PPV had several different from the three closely related CAEV p28s and from each other [10].

Biological context of Gsto1

• The full-length cDNA of 1.1 kb that was cloned contained an open reading frame coding for a previously unidentified 28-kDa mammalian protein, p28. p28 showed significant homologies to a large family of stress response proteins that contain a glutathione S-transferase (GST) domain [7].
• Although p28 is encoded from the first 1 kilobase at the 5' end of the genome, translation of in vitro-transcribed RNAs indicated that this protein was not detected unless the product of the entire 5.3-kilobase region was synthesized [11].
• In the absence of p28, the attenuation of EV pathogenicity can be explained by a failure of the virus to replicate in macrophage lineage cells at all successive steps in the spread of virus from the skin to its target organ, the liver [12].
• In macrophages infected with the p28- mutant, viral DNA replication was not detected, whereas the synthesis of at least two early proteins was observed [12].
• The p28 protein could not be cleaved from the smaller primary translation products of gene A, even in the presence of the larger autocleaving protein [11].

Anatomical context of Gsto1

• Following fractionation of the small membrane pellet on an iodixanol density gradient, the gene 1 proteins p28 and helicase cofractionated with dense membranes (1.12 to 1.13 g/ml) that also contained peak concentrations of N [13].
• Proteinase activity was monitored by examining the generation of p28 during in vitro translation in rabbit reticulocyte lysates [14].
• Here, we show that, unlike all tested cell cultures, the expression of p28 is required for in vitro replication of EV in murine resident peritoneal macrophages [12].
• Significant amounts of viral antigens were detected in the intestinal walls: both p28 and gp52 were found in the duodenum and small intestine [15].
• Moreover, the four viral antigens gp52, gp36, p28 and p8 were clearly observed in very large supranuclear vacuoles inside the epithelial cells of the distal part of the gut [15].

Associations of Gsto1 with chemical compounds

• This cysteine proteinase is responsible for the in vitro cleavage of p28, a polypeptide that is also present in MHV-A59-infected cells [16].
• Translation in the presence of the protease inhibitors leupeptin and ZnCl2 resulted in the disappearance of p28 and p220 and the appearance of a new protein, p250 [17].
• When viral DNA replication was inhibited with cytosine arabinoside, p28 was found in distinct, focal structures that may be precursors to the factories [12].
• Indirect immunofluorescence was used with three monospecific antisera to localize one envelope glycoprotein, gp47, and two core proteins, p28 and p8 [18].
• Treatment of sperm with the egg jelly, which activates Ca(2+) influx to induce the acrosome reaction, resulted in a significant elevation of the p28 content in the nucleus [19].

Analytical, diagnostic and therapeutic context of Gsto1

• One-dimensional peptide mapping with Staphylococcus aureus V-8 protease confirmed the precursor-product relationship of p250 and p28 [17].
• Immunofluorescence and biochemical analyses showed that in EV-infected macrophages or BSC-1 cells, p28 is associated with virus factories [12].
• This tumor expressed core- and envelope-related proteins detectable by immunoblotting (including p28, gp52, and gp36), displayed an acquired provirus with a restriction map different from those of described exogenous MMTV strains, and contained abundant virus particles [20].
• The amounts of antigens gp47 and p28 were measured by immunoassay in sera and organ extracts of corresponding samples of mice [18].
• The cell-free translation of virion RNA results in the synthesis of two predominant products p220 and p28 (M. R. Denison and S. Perlman, 1986, J. Virol. 60, 12-18). p28 is a basic protein and is readily detected by two-dimensional gel electrophoresis [21].

References