The L1 Retroelement-related p40 Protein Induces p38δ MAP Kinase
We characterized a full length L1 mRNA in a rheumatoid arthritis (RA) synovial tissue and determined the degree of methylation of its 5′-UTR. We asked whether not only intact but also altered L1s can exert biological activities by transfecting RA synovial fibroblasts (SF) with either retrotransposit...
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Published in | Autoimmunity (Chur, Switzerland) Vol. 37; no. 1; pp. 57 - 65 |
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Main Authors | , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Abingdon
Taylor & Francis
01.02.2004
Taylor and Francis |
Subjects | |
Online Access | Get full text |
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Summary: | We characterized a full length L1 mRNA in a rheumatoid arthritis (RA) synovial tissue and determined the degree of methylation of its 5′-UTR. We asked whether not only intact but also altered L1s can exert biological activities by transfecting RA synovial fibroblasts (SF) with either retrotransposition-competent or incompetent L1s and examined their capacity to induce p38δ. Total RNA was isolated from the synovial tissue of a 35-year-old woman with highly destructive RA. A complete L1 sequence was obtained by 3′/5′-RACE. Methylation of the genomic 5′-UTR was determined by the sodium-disulfide/PCR method. RA-SF were transfected by lipofection with either a functional L1 or an ORF2-mutated L1 element. The expression of p38δ was measured by RT-PCR and Western blot. The full length L1 mRNA included a 5′-UTR, an ORF1 and an ORF2. Three of five CpG islands (60%) of the genomic L1 5′-UTR were hypomethylated and the ORF2 was deactivated by the insertion of stop codons. Both, intact and ORF2-mutated L1 vectors, induced the expression of p38δ. Thus, even an ORF2-mutated L1 element, as expressed in RA, is biologically active and both L1 ORF1 and p38δ transcripts may appear as a consequence of genomic hypomethylation. The induction of p38δ appears to be mediated by an ORF1/p40-dependent process. This is the first indication of a p40 mediated transactivation. |
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ISSN: | 0891-6934 1607-842X |
DOI: | 10.1080/08916930310001637977 |