Matches in SemOpenAlex for { <https://semopenalex.org/work/W1561282213> ?p ?o ?g. }
Showing items 1 to 40 of
40
with 100 items per page.
- W1561282213 endingPage "15" @default.
- W1561282213 startingPage "15" @default.
- W1561282213 abstract "The success of tumor necrosis factor (TNF) antagonists in the therapy of inflammatory arthritides has established the central role of this cytokine in the pathogenesis of these disorders. TNF is notable in that it is predominantly controlled at the post-transcriptional level in macrophages. TNF biosynthesis is highly regulated by the AU-rich element (AURE) found in its 3' untranslated region. This AURE regulates both the stability and rate of translation of TNF mRNA. In the macrophage, the ERK, JNK, and p38 SAPK signaling pathways converge on the AURE in regulating the nuclear export, stability and translation of TNF mRNA. Second, the C3H zinc finger protein, tristetraprolin (TTP), appears to play a major role in the post-transcriptional regulation of TNF by binding the AURE. Recent studies have identified that TTP is a target of the p38 SAPK/MAPKAP K2 kinase (MK2) pathway. Phosphorylation of TTP by MK2 has been reported in vitro and in vivo; data suggest that MK2 activation inactivates the function of TTP as a destabilizing protein.Intriguingly, TTP binding to the AURE does not appear to be regulated by this phosphorylation. Rather, the function of TTP seems to be modulated through interactions with specific proteins that alter its subcellular localization. This creates a model where TTP provides specificity in binding cytokine-type AURE but the consequences of this interaction are determined by protein–protein interactions. Second, we have identified that TTP does not bind all AURE, but rather exhibits specificity for nUAUUUAUn sequences. Third, we have identified that TTP regulates its own mRNA stability. Fourth, we have demonstrated that TTP localizes to the polysomes in the context of macrophage activation by lipopolysaccharide. Fifth, we have demonstrated that TTP is expressed in many different hematopoietic cells and appears to function as an AURE binding protein. Thus, although the role of TTP in TNF biology is best understood in the macrophage, it appears that some, if not all, of these concepts may be relevant to other cells involved in the immune and inflammatory response." @default.
- W1561282213 created "2016-06-24" @default.
- W1561282213 creator A5075200726 @default.
- W1561282213 creator A5088403874 @default.
- W1561282213 date "2004-01-01" @default.
- W1561282213 modified "2023-09-27" @default.
- W1561282213 doi "https://doi.org/10.1186/ar1349" @default.
- W1561282213 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2833479" @default.
- W1561282213 hasPublicationYear "2004" @default.
- W1561282213 type Work @default.
- W1561282213 sameAs 1561282213 @default.
- W1561282213 citedByCount "0" @default.
- W1561282213 crossrefType "journal-article" @default.
- W1561282213 hasAuthorship W1561282213A5075200726 @default.
- W1561282213 hasAuthorship W1561282213A5088403874 @default.
- W1561282213 hasBestOaLocation W15612822131 @default.
- W1561282213 hasConcept C15744967 @default.
- W1561282213 hasConceptScore W1561282213C15744967 @default.
- W1561282213 hasIssue "Suppl 3" @default.
- W1561282213 hasLocation W15612822131 @default.
- W1561282213 hasLocation W15612822132 @default.
- W1561282213 hasOpenAccess W1561282213 @default.
- W1561282213 hasPrimaryLocation W15612822131 @default.
- W1561282213 hasRelatedWork W1862025210 @default.
- W1561282213 hasRelatedWork W19312449 @default.
- W1561282213 hasRelatedWork W2122410582 @default.
- W1561282213 hasRelatedWork W2143124181 @default.
- W1561282213 hasRelatedWork W2317566434 @default.
- W1561282213 hasRelatedWork W2410978906 @default.
- W1561282213 hasRelatedWork W2622204852 @default.
- W1561282213 hasRelatedWork W2949283095 @default.
- W1561282213 hasRelatedWork W4210534333 @default.
- W1561282213 hasRelatedWork W4255039225 @default.
- W1561282213 hasVolume "6" @default.
- W1561282213 isParatext "false" @default.
- W1561282213 isRetracted "false" @default.
- W1561282213 magId "1561282213" @default.
- W1561282213 workType "article" @default.