PubMed:19230833 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PubMed/sourceid/19230833","sourcedb":"PubMed","sourceid":"19230833","source_url":"http://www.ncbi.nlm.nih.gov/pubmed/19230833","text":"PKR-mediated degradation of STAT1 regulates osteoblast differentiation.\nThe double-stranded RNA-dependent protein kinase (PKR) plays a critical role in various biological responses including antiviral defense, cell differentiation, apoptosis, and tumorigenesis. In this study, we investigated whether PKR could affect the post-translational modifications of STAT1 protein and whether these modifications regulate osteoblast differentiation. We demonstrated that PKR was necessary for the ubiquitination of STAT1 protein. The expressions of bone-related genes such as type I collagen, integrin binding sialoprotein, osteopontin, and osterix were suppressed in osteoblasts lacking PKR activity. In contrast, the expressions of interleukin-6 and matrix metalloproteinases 8 and 13 increased in PKR-mutated osteoblasts. The expression and degradation of STAT1 protein were regulated by PKR in a SLIM-dependent pathway. Inhibition of SLIM by RNA interference resulted in the decreased activity of Runx2 in osteoblasts. Stimulation of interleukin-6 expression and suppression of alkaline phosphatase activity were regulated through by SLIM-dependent pathway. However, expressions of bone-related genes and MMPs were regulated by SLIM-independent pathway. Our present results suggest that the aberrant accumulation of STAT1 protein induced by loss of PKR regulate osteoblast differentiation through both SLIM/STAT1-dependent and -independent pathways.","tracks":[{"project":"bionlp-st-epi-2011-training","denotations":[{"id":"T1","span":{"begin":0,"end":3},"obj":"Protein"},{"id":"T2","span":{"begin":28,"end":33},"obj":"Protein"},{"id":"T3","span":{"begin":76,"end":120},"obj":"Protein"},{"id":"T4","span":{"begin":122,"end":125},"obj":"Protein"},{"id":"T5","span":{"begin":301,"end":304},"obj":"Protein"},{"id":"T6","span":{"begin":358,"end":363},"obj":"Protein"},{"id":"T7","span":{"begin":462,"end":465},"obj":"Protein"},{"id":"T8","span":{"begin":506,"end":511},"obj":"Protein"},{"id":"T9","span":{"begin":584,"end":613},"obj":"Protein"},{"id":"T10","span":{"begin":615,"end":626},"obj":"Protein"},{"id":"T11","span":{"begin":632,"end":639},"obj":"Protein"},{"id":"T12","span":{"begin":679,"end":682},"obj":"Protein"},{"id":"T13","span":{"begin":725,"end":738},"obj":"Protein"},{"id":"T14","span":{"begin":743,"end":770},"obj":"Protein"},{"id":"T15","span":{"begin":775,"end":777},"obj":"Protein"},{"id":"T16","span":{"begin":791,"end":794},"obj":"Protein"},{"id":"T17","span":{"begin":850,"end":855},"obj":"Protein"},{"id":"T18","span":{"begin":882,"end":885},"obj":"Protein"},{"id":"T19","span":{"begin":891,"end":895},"obj":"Protein"},{"id":"T20","span":{"begin":929,"end":933},"obj":"Protein"},{"id":"T21","span":{"begin":992,"end":997},"obj":"Protein"},{"id":"T22","span":{"begin":1029,"end":1042},"obj":"Protein"},{"id":"T23","span":{"begin":1073,"end":1093},"obj":"Protein"},{"id":"T24","span":{"begin":1129,"end":1133},"obj":"Protein"},{"id":"T25","span":{"begin":1223,"end":1227},"obj":"Protein"},{"id":"T26","span":{"begin":1311,"end":1316},"obj":"Protein"},{"id":"T27","span":{"begin":1344,"end":1347},"obj":"Protein"},{"id":"T28","span":{"begin":1397,"end":1401},"obj":"Protein"},{"id":"T29","span":{"begin":1402,"end":1407},"obj":"Protein"}],"attributes":[{"subj":"T1","pred":"source","obj":"bionlp-st-epi-2011-training"},{"subj":"T2","pred":"source","obj":"bionlp-st-epi-2011-training"},{"subj":"T3","pred":"source","obj":"bionlp-st-epi-2011-training"},{"subj":"T4","pred":"source","obj":"bionlp-st-epi-2011-training"},{"subj":"T5","pred":"source","obj":"bionlp-st-epi-2011-training"},{"subj":"T6","pred":"source","obj":"bionlp-st-epi-2011-training"},{"subj":"T7","pred":"source","obj":"bionlp-st-epi-2011-training"},{"subj":"T8","pred":"source","obj":"bionlp-st-epi-2011-training"},{"subj":"T9","pred":"source","obj":"bionlp-st-epi-2011-training"},{"subj":"T10","pred":"source","obj":"bionlp-st-epi-2011-training"},{"subj":"T11","pred":"source","obj":"bionlp-st-epi-2011-training"},{"subj":"T12","pred":"source","obj":"bionlp-st-epi-2011-training"},{"subj":"T13","pred":"source","obj":"bionlp-st-epi-2011-training"},{"subj":"T14","pred":"source","obj":"bionlp-st-epi-2011-training"},{"subj":"T15","pred":"source","obj":"bionlp-st-epi-2011-training"},{"subj":"T16","pred":"source","obj":"bionlp-st-epi-2011-training"},{"subj":"T17","pred":"source","obj":"bionlp-st-epi-2011-training"},{"subj":"T18","pred":"source","obj":"bionlp-st-epi-2011-training"},{"subj":"T19","pred":"source","obj":"bionlp-st-epi-2011-training"},{"subj":"T20","pred":"source","obj":"bionlp-st-epi-2011-training"},{"subj":"T21","pred":"source","obj":"bionlp-st-epi-2011-training"},{"subj":"T22","pred":"source","obj":"bionlp-st-epi-2011-training"},{"subj":"T23","pred":"source","obj":"bionlp-st-epi-2011-training"},{"subj":"T24","pred":"source","obj":"bionlp-st-epi-2011-training"},{"subj":"T25","pred":"source","obj":"bionlp-st-epi-2011-training"},{"subj":"T26","pred":"source","obj":"bionlp-st-epi-2011-training"},{"subj":"T27","pred":"source","obj":"bionlp-st-epi-2011-training"},{"subj":"T28","pred":"source","obj":"bionlp-st-epi-2011-training"},{"subj":"T29","pred":"source","obj":"bionlp-st-epi-2011-training"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"bionlp-st-epi-2011-training","color":"#9397ec","default":true}]}]}}