Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0014070 (encephalomyelitis)
 13,017 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The PLE21/HuC neural protein is an autoantigen for anti-neuronal nuclear autoantibodies (ANNA-1/anti-Hu/Type IIa antibodies) from a patient with paraneoplastic limbic encephalomyelitis and small cell lung carcinoma. This antigen belongs to the Hu/ELAV-like protein family, contains three RNA recognition motifs (RRMs) and has RNA binding capacity. In many autoimmune diseases mediated by autoantibodies, antibodies often interfere with the biological functions of their target antigens. To investigate the influences of the autoantibodies on the biological function of the antigen, we mapped the regions which were required for the antibody recognition and for the RNA binding. Deletion analysis of the antigen revealed that the epitopes for the antibodies were localized in the regions of 12 residues, amino acids 161-172, and eight residues, amino acids 29-38, of the first and second RRMs. It was also shown that the eight residues, amino acids 29-38, and the 10 residues, amino acids 187-194, were required for the RNA binding. Although amino acids 29-38 were necessary for both the antibody recognition and the RNA bindings, pre-incubation of the PLE21 antigen with the antibodies did not inhibit the formation of the complex of PLE21, the antibodies and RNA. Thus, the regions required for the antibody recognition are not identical with those for the RNA binding, and it seems unlikely that the autoantibodies interfere with RNA binding of the antigen.
 ...
PMID:Antibody recognition and RNA binding of a neuronal nuclear autoantigen associated with paraneoplastic neurological syndromes and small cell lung carcinoma. 1037 67

The CD154 molecule is important for experimental allergic encephalomyelitis (EAE) which is mediated by autoimmune CD4(+) T-cells. Post-transcriptional instabilization/stabilization of mRNAs, which contain an adenylate uridylate rich element (ARE) in their 3' untranslated region (3'UTR), is regulated in part by binding of ARE-binding proteins to the element. We have investigated the protein which binds to the nonameric ARE in the 3'UTR of CD154 mRNA. A protein which binds to the CD154 ARE was found to exist in a extract prepared from murine autoimmune T-cells activated with myelin basic protein (MBP), and turned out to be mHuR which is a ubiquitous ELAV-like protein. It was found that mHuR was upregulated upon stimulation of the T-cells with a MBP antigen. The CD154 ARE and the ARE in the 3'UTR of tumor necrosis factor-alpha (TNF-alpha) mRNA were competed in binding to mHuR, indicating that both AREs bind to the same site on mHuR. The presence of the CD154 ARE downstream of the luciferase cDNA in a reporter plasmid decreased the translational efficiency, and co-expression of the mHuR slightly increased the translation. These results suggest the possibility that the ELAV-like protein participates in the regulation of the expression of CD154 on the autoimmune T-cells. Modification of the expression of CD154 on autoimmune T-cells by regulating the ELAV-like protein may provide effective therapy for EAE and human multiple sclerosis.
 ...
PMID:Binding of the ELAV-like protein in murine autoimmune T-cells to the nonameric AU-rich element in the 3' untranslated region of CD154 mRNA. 1268 4

n-ELAV (neuronal-Embryonic Lethal, Abnormal Vision)-like genes belong to a family codifying for onconeural RNA-binding proteins, also called Hu antigens. Anti-Hu-antibodies (anti-Hu-Ab) are typically associated with paraneoplastic encephalomyelitis/sensory neuropathy (PEM/PSN), and low titres of anti-Hu-Ab were found in neural/neuroendocrine neoplasms, especially small cell lung cancer (SCLC). To date, few studies have been published focused on the genetic causes of their involvement in the pathogenesis of neuroendocrine tumors (NE). Here we analyzed 20 primary human neuroendocrine lung tumor tissues for somatic mutations in the HuD gene. Two inactivating mutations (a frameshift and a stop codon mutation) and 11 nucleotide changes were detected in the coding sequence of HuD gene in 7 different lung tumors. Our results on SCLC and carcinoid tissues support the hypothesis that alterations of nELAV genes could be involved in the onset and/or progression of a subset of neuroendocrine lung tumors.
 ...
PMID:Molecular analysis of the HuD gene in neuroendocrine lung cancers. 1941 Mar 29