Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0409974 (lupus)
 22,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In response to the pure recombinant human alpha-IFN, IFLrA, Raji and Daudi were the only two cell lines among 19 human lymphoblastoid cell lines tested that formed the human lupus inclusions (LI) to a high frequency. Raji, Daudi, and five other cell lines were examined for protein changes that might accompany LI formation. Their selection was based upon T or B origin, association with Epstein-Barr virus, and ability to form LI. A trace protein of an estimated molecular mass of 36 kD (p36) and an isoelectric point of 5.6 was detected on two-dimensional gels only of alpha-IFN-treated Raji and Daudi cells. Gamma-IFN did not induce p36 or LI in any of these seven cell lines. In Daudi cells p36 and LI formed simultaneously in response to IFLrA, and persisted until the alpha-IFN-induced death of the culture. In Raji cells, p36 and LI appearance and disappearance coincided with the addition and removal of alpha-IFN. Fractionation of Raji cells with nonionic-detergent buffer placed p36 with the inclusions in the cytoplasmic supernatant. With detergent-free buffer p36 and LI were distributed evenly between the nuclear and cytoplasmic fractions. Pulse-chase experiments revealed that p36 was secreted. The de novo synthesis of p36 with alpha-IFN treatment was shown by labeling the cell proteins with [35S] methionine before and after the addition of alpha-IFN. These results along with previous results on the de novo synthesis of LI in the endoplasmic reticulum (which is involved in the processing and secretion of proteins) suggest a role for LI in the synthesis and secretion of p36.
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PMID:De novo synthesis and secretion of a 36-kD protein by cells that form lupus inclusions in response to alpha-interferon. 781 19

The trace interferon-alpha-induced protein, p36, was induced in Raji cells in association with lupus inclusions. It was solubilized in a nonionic detergent buffer, enriched by differential centrifugation and by preparative isoelectric focusing, and purified to homogeneity on two-dimensional protein gels. Failure to obtain N-terminal amino acid sequence, however, suggested a blocked alpha-amino group. Sequences of six tryptic peptides, 13-19 amino acids in length, were obtained after digestion, microbore-high performance liquid chromotography purification, and chemical sequence analysis. None of the six sequences, which represented approximately 25% of the entire protein, shared any meaningful homologies with entries in protein sequence repositories. Raji-cell p36 was shown in Western blots with antipeptide antibodies to be induced at least 400-fold and by immunofluorescence microscopy to co-localize with the endoplasmic reticulum resident protein, protein disulfide isomerase. These results show that p36 is a new interferon-alpha-induced protein that localizes in the endoplasmic reticulum, the cell region in which the lupus inclusions form, and that p36 is probably physically associated with the lupus inclusions.
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PMID:Purification, microsequencing, and immunolocalization of p36, a new interferon-alpha-induced protein that is associated with human lupus inclusions. 855 39

Previous work showed that IFN-alpha induced the autoimmune-associated lupus inclusions (LI) in all 16 umbilical cord mononuclear cell samples from healthy mothers. In contrast, IFN-alpha induced LI and the LI-associated protein, p36, in only 2 of 16 human B lymphoblastoid cell lines. Resistance of these 14 cell lines to form LI and p36 may be due to their stage of development or differentiation or their transformed state. We sought to determine whether aging, neoplastic transformation, and HIV infection affected the observed IFN-alpha induction of LI in cord blood mononuclear cells. Expression of LI and p36 was investigated in PBMC on IFN-alpha chemotherapy and on culturing IFN-alpha with PBMC samples prepared from healthy adults and AIDS patients. The IFN-alpha induction of LI (detected by electron microscopy) or p36 (detected by two-dimensional gels) in all of the PBMC samples from these individuals was indistinguishable from the cord blood mononuclear cell response. Furthermore, induction of p36 and LI was not a good indicator of effective IFN-alpha chemotherapy. It may be consequential for autoimmunity induced by IFN-alpha in cancer, AIDS, and systemic lupus erythematosus (SLE). An essential biologic role for p36 and LI is suggested by a highly homologous p36 gene in the invertebrate Caenorhabditis elegans.
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PMID:Interferon-alpha-induced human lupus inclusions and p36 protein in cancer and AIDS. 888 55

We describe here the first full-length sequence of a member of a novel gene family encoding a protein in the mouse that we call Lupin. Lupin is homologous to a human protein previously called p36, which was purified from alpha-interferon-treated cells that formed lupus inclusions. Lupus inclusions are dense intracellular deposits found in endothelial cells and lymphocytes of patients with systemic lupus erythematosis and AIDS. Proteins closely related to Lupin exist in evolutionarily divergent species including Caenorhabditis elegans, Drosophila and zebrafish. At least one other lupin-related gene is expressed in the mouse and in man. Lupin is expressed in mouse embryos and adults, notably in liver, spleen, central nervous system, multiple epithelia and all types of muscle. In skeletal muscle, expression analysis suggests that Lupin associates with the contractile apparatus.
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PMID:Cloning and expression analysis of murine lupin, a member of a novel gene family that is conserved through evolution and associated with Lupus inclusions. 1118 Aug