The L1 retroelement-related p40 protein induces p38delta MAP kinase

Autoimmunity. 2004 Feb;37(1):57-65. doi: 10.1080/08916930310001637977.


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 p38delta. 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 p38delta 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 p38delta. Thus, even an ORF2-mutated L1 element, as expressed in RA, is biologically active and both L1 ORF1 and p38delta transcripts may appear as a consequence of genomic hypomethylation. The induction of p38delta appears to be mediated by an ORF1/p40-dependent process. This is the first indication of a p40 mediated transactivation.

MeSH terms

  • Arthritis, Rheumatoid / genetics
  • Arthritis, Rheumatoid / metabolism
  • Blotting, Western
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization
  • Mitogen-Activated Protein Kinase 13
  • Mitogen-Activated Protein Kinases / genetics
  • Mitogen-Activated Protein Kinases / metabolism*
  • Phylogeny
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Retroelements / genetics*


  • DNA-Binding Proteins
  • RNA, Messenger
  • Retroelements
  • L1Hs-encoded protein p40, human
  • Mitogen-Activated Protein Kinase 13
  • Mitogen-Activated Protein Kinases