Down-regulation of asymmetric arginine methylation during replicative and H2O2-induced premature senescence in WI-38 human diploid fibroblasts

Yongchul Lim, Eunil Lee, Joohyun Lee, Sangnam Oh, Sangduk Kim

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Protein arginine methylation is one of the post-translational modifications which yield monomethyl and dimethyl (asymmetric or symmetric) arginines in proteins. In the present study, we investigated the status of protein arginine methylation during human diploid fibroblast senescence. When the expression of protein arginine methyltransferases (PRMTs), namely PRMT1, PRMT4, PRMT5 and PRMT6 was examined, a significant reduction was found in replicatively senescent cells as well as their catalytic activities against histone mixtures compared with the young cells. Furthermore, when the endogenous level of arginine-dimethylated proteins was determined, asymmetric modification (the product of type I PRMTs including PRMT1, PRMT4 and PRMT6) was markedly down-regulated. In contrast, both up- and down-regulations of symmetrically arginine-methylated proteins (the product of type II PRMTs including PRMT5) during replicative senescence were found. Furthermore, when young fibroblasts were induced to premature senescence by sub-cytotoxic H2O2 treatment, results similar to replicative senescence were obtained. Finally, we found that SV40-mediated immortalized WI-38 and HeLa cell lines maintained a higher level of asymmetrically modified proteins as well as type I PRMTs than young fibroblasts. These results suggest that the maintenance of asymmetric modification in the expressed target proteins of type I PRMTs might be critical for cellular proliferation.

Original languageEnglish
Pages (from-to)523-529
Number of pages7
JournalJournal of Biochemistry
Volume144
Issue number4
DOIs
Publication statusPublished - 2008 Oct

Keywords

  • Dimethylarginines
  • HO -induced premature senescence
  • Human diploid fibroblasts
  • Protein arginine methyltransferases
  • Replicative senescence

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

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