| http://purl.uniprot.org/citations/20595389 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/20595389 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/20595389 | http://www.w3.org/2000/01/rdf-schema#comment | "Tristetraprolin (TTP) directs its target AU-rich element (ARE)-containing mRNAs for degradation by promoting removal of the poly(A) tail. The p38 MAPK pathway regulates mRNA stability via the downstream kinase MAPK-activated protein kinase 2 (MAPKAP kinase 2 or MK2), which phosphorylates and prevents the mRNA-destabilizing function of TTP. We show that deadenylation of endogenous ARE-containing tumor necrosis factor mRNA is inhibited by p38 MAPK. To investigate whether phosphorylation of TTP by MK2 regulates TTP-directed deadenylation of ARE-containing mRNAs, we used a cell-free assay that reconstitutes the mechanism in vitro. We find that phosphorylation of Ser-52 and Ser-178 of TTP by MK2 results in inhibition of TTP-directed deadenylation of ARE-containing RNA. The use of 14-3-3 protein antagonists showed that regulation of TTP-directed deadenylation by MK2 is independent of 14-3-3 binding to TTP. To investigate the mechanism whereby TTP promotes deadenylation, it was necessary to identify the deadenylases involved. The carbon catabolite repressor protein (CCR)4.CCR4-associated factor (CAF)1 complex was identified as the major source of deadenylase activity in HeLa cells responsible for TTP-directed deadenylation. CAF1a and CAF1b were found to interact with TTP in an RNA-independent fashion. We find that MK2 phosphorylation reduces the ability of TTP to promote deadenylation by inhibiting the recruitment of CAF1 deadenylase in a mechanism that does not involve sequestration of TTP by 14-3-3. Cyclooxygenase-2 mRNA stability is increased in CAF1-depleted cells in which it is no longer p38 MAPK/MK2-regulated."xsd:string |
| http://purl.uniprot.org/citations/20595389 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m110.136473"xsd:string |
| http://purl.uniprot.org/citations/20595389 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m110.136473"xsd:string |
| http://purl.uniprot.org/citations/20595389 | http://purl.uniprot.org/core/author | "Dean J.L."xsd:string |
| http://purl.uniprot.org/citations/20595389 | http://purl.uniprot.org/core/author | "Dean J.L."xsd:string |
| http://purl.uniprot.org/citations/20595389 | http://purl.uniprot.org/core/author | "Clark A.R."xsd:string |
| http://purl.uniprot.org/citations/20595389 | http://purl.uniprot.org/core/author | "Clark A.R."xsd:string |
| http://purl.uniprot.org/citations/20595389 | http://purl.uniprot.org/core/author | "Saklatvala J."xsd:string |
| http://purl.uniprot.org/citations/20595389 | http://purl.uniprot.org/core/author | "Saklatvala J."xsd:string |
| http://purl.uniprot.org/citations/20595389 | http://purl.uniprot.org/core/author | "Aubareda A."xsd:string |
| http://purl.uniprot.org/citations/20595389 | http://purl.uniprot.org/core/author | "Aubareda A."xsd:string |
| http://purl.uniprot.org/citations/20595389 | http://purl.uniprot.org/core/author | "Tudor C."xsd:string |
| http://purl.uniprot.org/citations/20595389 | http://purl.uniprot.org/core/author | "Tudor C."xsd:string |
| http://purl.uniprot.org/citations/20595389 | http://purl.uniprot.org/core/author | "Marchese F.P."xsd:string |
| http://purl.uniprot.org/citations/20595389 | http://purl.uniprot.org/core/author | "Marchese F.P."xsd:string |
| http://purl.uniprot.org/citations/20595389 | http://purl.uniprot.org/core/date | "2010"xsd:gYear |
| http://purl.uniprot.org/citations/20595389 | http://purl.uniprot.org/core/date | "2010"xsd:gYear |
| http://purl.uniprot.org/citations/20595389 | http://purl.uniprot.org/core/name | "J. Biol. Chem."xsd:string |
| http://purl.uniprot.org/citations/20595389 | http://purl.uniprot.org/core/name | "J. Biol. Chem."xsd:string |
| http://purl.uniprot.org/citations/20595389 | http://purl.uniprot.org/core/pages | "27590-27600"xsd:string |
| http://purl.uniprot.org/citations/20595389 | http://purl.uniprot.org/core/pages | "27590-27600"xsd:string |
| http://purl.uniprot.org/citations/20595389 | http://purl.uniprot.org/core/title | "MAPKAP kinase 2 blocks tristetraprolin-directed mRNA decay by inhibiting CAF1 deadenylase recruitment."xsd:string |
| http://purl.uniprot.org/citations/20595389 | http://purl.uniprot.org/core/title | "MAPKAP kinase 2 blocks tristetraprolin-directed mRNA decay by inhibiting CAF1 deadenylase recruitment."xsd:string |