Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P01889 (ankylosing spondylitis)
 5,717 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Five HLA-B27 subtypes, B*2701, B*2703, B*2704, B*2705, and B*2706, were tested for direct binding with twenty-six synthetic nonapeptides carrying the primary anchor residue motifs (combination of amino residues at positions 2 and 9) relevant to B*2705. The peptide sequences were derived from human HSP89 alpha, P53 and MBP. The alpha chains were immunospecifically isolated from LH (B*2701), CH (B*2703), WE1 (B*2704), BTB (B*2705), and LIE (B*2706) cells and their peptide binding was measured by the HLA class I alpha chain refolding assay. The data obtained indicated that the B27 subtypes tested can bind a common set of peptides carrying several different anchor residue motifs. The motifs, R-K and R-R, reported for B*2705 and a new motif H-R were accepted by B*2703, B*2704, and B*2706, but not by B*2701. However, other motifs, including known B*2702 and/or B*2705 motifs, R-H, R-L, R-A, and R-F, and a new motif found here, R-G, were apparently accepted by all B27 subtypes tested. The observed cross-peptide binding in the B27 subgroup is compatible with the so-called arthritogenic peptide hypothesis in the pathogenesis of ankylosing spondylitis.
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PMID:The peptide binding specificity of HLA-B27 subtypes. 803 27

p53 mutations are frequently found in human cancers and are often associated with the overexpression of wild-type (WT) protein or peptide sequences, supporting the notion that WT p53 epitopes may serve as potential targets for tumor immunotherapy. We have developed a cytotoxic T lymphocyte (CTL)/p53 tumor-associated antigen (TAA) model, based on immune recognition of a WT p53 determinant. WT p53-peptide-specific, major histocompatibility complex (MHC) classI-restricted CTL were produced from immunocompetent C57BL/6 (H-2b) mice after immunization with a previously defined WT p53 peptide (p53(232-240)) Epitope-specific CTL were then employed to identify syngeneic tumor cell populations expressing that antigenic determinant. Two syngeneic tumor cell lines, MC38 colon carcinoma and MC57G fibrosarcoma, were demonstrated to express the endogenous WT p53(232-240) determinant naturally, as defined by CD8 + CTL recognition. Cold-target inhibition assays confirmed that CTL-mediated lysis was due to immune recognition of the p53(232-240) peptide epitope. The p53(232-240)-specific CTL line did not lyse syngeneic normal cells (i.e., mitogen-activated splenocytes) in the absence of exogenous peptide, suggesting that the WT-p53-specific CTL could distinguish between tumor cells expressing self-TAA and normal host cells. We have demonstrated, for the first time, that the adoptive transfer of WT-p53-specific CTL to mice with established pulmonary metastasis resulted in antitumor activity in vivo. The ability to generate MHC-class-I-restricted CD8- CTL lines specific for a non-mutated p53 determinant from normal, immunocompetent mice, which display antitumor activity both in vitro and in vivo (by adoptive transfer), may have implications for the immunotherapy of certain p53-expressing malignancies.
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PMID:Characterization of CD8+ cytotoxic T lymphocyte/tumor cell interactions reflecting recognition of an endogenously expressed murine wild-type p53 determinant. 1122 91

Ankylosing spondylitis (AS) is a chronic rheumatic disease that mainly affects the spinal joints (vertebrae). Spondylitis means inflammation of the spine, and ankylosing spondylitis means that bones tend to fuse. The AS causes the vertebrae to swell in the spine. Therefore, based on protein interaction network analysis, we conducted in-depth research on the molecular mechanism of key regulatory factors in the AS disease process. We carried out a differential analysis of the expression of miRNAs in disease samples and miRNAs in normal samples. Protein network interaction analysis is performed according to a group of target genes regulated by significant differentially expressed miRNAs and clustered into an interaction module. In addition, enrichment analysis of functions and pathways was performed on these modular genes. Based on the predictive analysis of multidimensional regulators, we identified a range of regulatory factors that have potential regulatory effects on AS, such as endogenous genes and transcription factors. We obtained 20 differentially expressed miRNAs and 7082 target genes and clustered into 11 modules. Enrichment results showed that these modular genes are mainly involved in the functions and pathways of protein polyubiquitination, neutrophil activation involved in immune response, and Wnt signaling pathway. We revealed ten transcription factors (MYC, NFKB1, and TP53). After network connectivity analysis, we obtained 12 internal drive genes (UBE2D1, CCNF, and NEDD4). These core genes are thought to be potential regulators of AS. MYC is also considered to be a core factor that inhibits SART3 phosphorylation and plays a vital role in the immunological pathogenesis of AS. The combination of the above analysis results can provide a new idea for biologists and medical scientists to study the immune pathogenesis of AS and can provide a valuable reference for subsequent treatment options.
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PMID:Potential regulatory factors in the pathogenesis of ankylosing spondylitis. 3304 Aug 22