Structure/function analysis of tristetraprolin (TTP): p38 stress-activated protein kinase and lipopolysaccharide stimulation do not alter TTP function.

摘要: Tristetraprolin (TTP) is the only trans-acting factor shown to be capable of regulating AU-rich element-dependent mRNA turnover at level intact animal; however, mechanism by which TTP mediated RNA instability unknown. Using an established model system, we performed structure/function analysis with as well examined current hypothesis that function regulated p38-MAPKAP kinase 2 (MK2) activation. Deletion either N- or C-terminal domains inhibited function. Extensive mutagenesis, up 16%, serines and threonines, some were predicted mediate proteasomal targeting, did not alter human Mutation conserved MK2 phosphorylation sites enhanced in both resting p38-stress-activated protein kinase-MK2-activated cells. However, kinase-MK2 activation activity wild-type mutant TTP. localized stress granules, arsenite treatment reducing this localization. In contrast, granule localization mutant, consistent involvement additional pathways event. Finally, determined that, response LPS stimulation, moves onto polysomes, movement occurs absence 14-3-3. Taken together, these data indicate although p38 alters entry into granule, it does Moreover, interaction 14-3-3, may limit involved downstream message stabilization events.