| First Author | Neininger A | Year | 2002 |
| Journal | J Biol Chem | Volume | 277 |
| Issue | 5 | Pages | 3065-8 |
| PubMed ID | 11741878 | Mgi Jnum | J:74321 |
| Mgi Id | MGI:2158083 | Doi | 10.1074/jbc.C100685200 |
| Citation | Neininger A, et al. (2002) MK2 targets AU-rich elements and regulates biosynthesis of tumor necrosis factor and interleukin-6 independently at different post-transcriptional levels. J Biol Chem 277(5):3065-8 |
| abstractText | We demonstrate that lipopolysaccharide-induced tumor necrosis factor (TNF) biosynthesis becomes independent of MAPKAP kinase 2 (MK2) when the AU-rich element (ARE) of the TNF gene is deleted. In spleen cells and macrophages where TNF biosynthesis is restored as a result of this deletion, interleukin (IL)-6 biosynthesis is still dependent on MK2. In MK2-deficient macrophages the half-life of IL-6 mRNA is reduced more than 10-fold, whereas the half-life of TNF mRNA is only weakly decreased. It is shown that the stability of a reporter mRNA carrying the AU-rich 3'-untranslated region (3'-UTR) of IL-6 is increased by MK2. The data provide in vivo evidence that the AU-rich 3'-UTRs of TNF and IL-6 are downstream to MK2 signaling and make MK2 an essential component of mechanisms that regulate biosynthesis of IL-6 at the levels of mRNA stability, and of TNF mainly through TNF-ARE-dependent translational control. |
