Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0079731 (B-cell lymphoma)
 16,671 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 72/74-kDa peptide binding protein (PBP72/74) was previously described which plays a role in the processing and/or presentation of Ag, possibly by facilitating the association of processed Ag with the MHC class II molecules. PBP72/74 was recently shown to be related to the 70-kDa family of heat shock proteins (hsp70), whose members show the general characteristic of binding to denatured or inappropriately folded proteins. Here we describe the cellular and subcellular distribution of PBP72/74. By flow cytometry with PBP72/74-specific rabbit antisera, PBP72/74 is detected on the surfaces of mouse Ig+ B cells and MAC-1+ macrophages. PBP72/74 74 was not detected on the surfaces of Thy-1+ T cells or NK1.1+ NK cells. The cell surface expression of PBP72/74 does not require MHC class II expression. Indeed, the Ia- variant B cell lymphoma cell line, M12.C3, expresses PBP72/74 at levels equivalent to that of the Ia+ parent cell line, M12.4.1, from which it was derived. Furthermore, the fibroblast L cell line, DAP.3, shows no cell surface expression of PBP72/74, nor do DAP.3 lines transfected with and expressing genes encoding the alpha- and beta-chain of the I-Ad and I-Ed molecules. Moreover, treatment of B cells with either IL-4 or LPS, which increases Ia expression severalfold, does not affect PBP72/74 expression. Thus, PBP72/74 cell surface expression appears to be a property of B cells and macrophages, independent of Ia expression. In addition, the B cell surface expression of PBP72/74 is not altered by stress in the form of heat shock. Thus, PBP72/74 appears to be a constitutive noninducible member of the hsp70 family. By immunoelectron microscopy, PBP72/74 is detected in approximately 36% of early endocytic vesicles into which surface Ig is internalized after binding to anti-Ig antibodies. This compartment was previously shown to contain class II en route to the cell surface associated with invariant chain and the proteases cathepsin B and D and is suggested to be a subcellular site of antigen processing. PBP72/74 is also found associated with the plasma membrane, endoplasmic reticulum, and membranes proximal to the Golgi stacks. The cellular and subcellular distribution of PBP72/74 is consistent with its playing a role in the processing of presentation of Ag with the MHC class II molecules.
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PMID:Cellular and subcellular distribution of PBP72/74, a peptide-binding protein that plays a role in antigen processing. 198 75

Death-associated protein-kinase(DAP-Kinase) is a pro-apoptotic serine/threonine kinase with a death domain, which is involved in apoptosis induced by interferon-gamma, tumor necrosis factor-alpha, and Fas ligand. Epigenetic down-regulation of DAP-Kinase gene expression by hypermethylation of its promoter region was reported in certain kinds of malignancies. Previous patho-epidemiological studies indicated that thyroid lymphoma(TL) evolves among active lymphoid cells in chronic lymphocytic thyroiditis(CLTH). With the use of methylation specific polymerase chain reaction, methylation status of DAP-Kinase CpG island was examined in thyroid lesions of 19 cases with TL and 9 with CLTH. Frequency of methylation was higher in TL cases(16 of 19, 84.2%) than in CLTH cases(2 of 9, 22.2%) (p < 0.01). DNA extracted from peripheral blood leukocytes from TL and CLTH cases never showed methylation, indicating that the methylation occurred somatically in lesional lymphocytes in the thyroid. We also examined the methylation status of DAP-kinase gene in 16 cases of T-cell malignancies including eight adult T-cell leukemia/lymphoma and 24 NK/T-cell, 34 B-cell, and two immunophenotypically undetermined lymphomas. Frequency of methylation was higher in B-cell(27 of 34, 79.4%) than in T-cell malignancies(eight of 16, 50%) (p < 0.05). Fifteen of 24(62.5%) NK/T-cell lymphomas showed DNA methylation. Hematopoietic cell lines with a methylated gene were resistant to apoptosis. Treatment of the cells with a demethylating agent restored apoptotic cell death in one B-cell lymphoma cell line with DNA methylation. Our results suggested that suppression of DAP-Kinase expression by DNA methylation might play a role in the development of B-cell malignancies.
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PMID:[Hypermethylation of DAP-kinase gene CpG Island in malignant lymphoma with B-cell phenotype]. 1179 95