| http://purl.uniprot.org/citations/28548957 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/28548957 | http://www.w3.org/2000/01/rdf-schema#comment | "Early release of tumor necrosis factor-alpha (TNF-α) during radiotherapy of thoracic cancers plays an important role in radiation pneumonitis, whose inhibition may provide lung radioprotection. We previously reported radiation inactivates Tristetraprolin (TTP), a negative regulator of TNF-α synthesis, which correlated with increased TNF-α release. However, the molecular events involved in radiation-induced TTP inactivation remain unclear. To determine if eliminating Ttp in mice resulted in a phenotypic response to radiation, Ttp-null mice lungs were exposed to a single dose of 15 Gy, and TNF-α release and lung inflammation were analyzed at different time points post-irradiation. Ttp-/-mice with elevated (9.5±0.6 fold) basal TNF-α showed further increase (12.2±0.9 fold, p<0.02) in TNF-α release and acute lung inflammation within a week post-irradiation. Further studies using mouse lung macrophage (MH-S), human lung fibroblast (MRC-5), and exogenous human TTP overexpressing U2OS and HEK293 cells upon irradiation (a single dose of 4 Gy) promoted p38-mediated TTP phosphorylation at the serine 186 position, which primed it to be recognized by an ubiquitin ligase (E3), beta transducing repeat containing protein (β-TrCP), to promote polyubiquitination-mediated proteasomal degradation. Consequently, a serine 186 to alanine (SA) mutant of TTP was resistant to radiation-induced degradation. Similarly, either a p38 kinase inhibitor (SB203580), or siRNA-mediated β-TrCP knockdown, or overexpression of dominant negative Cullin1 mutants protected TTP from radiation-induced degradation. Consequently, SB203580 pretreatment blocked radiation-induced TNF-α release and radioprotected macrophages. Together, these data establish the involvement of the p38-βTrCP-TTP-TNFα signaling axis in radiation-induced lung inflammation and identified p38 inhibition as a possible lung radioprotection strategy."xsd:string |
| http://purl.uniprot.org/citations/28548957 | http://purl.org/dc/terms/identifier | "doi:10.18632/oncotarget.17770"xsd:string |
| http://purl.uniprot.org/citations/28548957 | http://purl.uniprot.org/core/author | "Shukla S."xsd:string |
| http://purl.uniprot.org/citations/28548957 | http://purl.uniprot.org/core/author | "Ray P."xsd:string |
| http://purl.uniprot.org/citations/28548957 | http://purl.uniprot.org/core/author | "Ray D."xsd:string |
| http://purl.uniprot.org/citations/28548957 | http://purl.uniprot.org/core/author | "Lawrence T.S."xsd:string |
| http://purl.uniprot.org/citations/28548957 | http://purl.uniprot.org/core/author | "Mehra R."xsd:string |
| http://purl.uniprot.org/citations/28548957 | http://purl.uniprot.org/core/author | "Nyati M.K."xsd:string |
| http://purl.uniprot.org/citations/28548957 | http://purl.uniprot.org/core/author | "Krishnamurthy P.M."xsd:string |
| http://purl.uniprot.org/citations/28548957 | http://purl.uniprot.org/core/date | "2017"xsd:gYear |
| http://purl.uniprot.org/citations/28548957 | http://purl.uniprot.org/core/name | "Oncotarget"xsd:string |
| http://purl.uniprot.org/citations/28548957 | http://purl.uniprot.org/core/pages | "47767-47779"xsd:string |
| http://purl.uniprot.org/citations/28548957 | http://purl.uniprot.org/core/title | "Involvement of p38-betaTrCP-Tristetraprolin-TNFalpha axis in radiation pneumonitis."xsd:string |
| http://purl.uniprot.org/citations/28548957 | http://purl.uniprot.org/core/volume | "8"xsd:string |
| http://purl.uniprot.org/citations/28548957 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/28548957 |
| http://purl.uniprot.org/citations/28548957 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/28548957 |
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