PubMed:15047715 JSONTXT

{"project":"sentences","denotations":[{"id":"T1","span":{"begin":0,"end":88},"obj":"Sentence"},{"id":"T2","span":{"begin":89,"end":201},"obj":"Sentence"},{"id":"T3","span":{"begin":202,"end":326},"obj":"Sentence"},{"id":"T4","span":{"begin":327,"end":480},"obj":"Sentence"},{"id":"T5","span":{"begin":481,"end":588},"obj":"Sentence"},{"id":"T6","span":{"begin":589,"end":674},"obj":"Sentence"},{"id":"T7","span":{"begin":675,"end":741},"obj":"Sentence"},{"id":"T8","span":{"begin":742,"end":868},"obj":"Sentence"},{"id":"T9","span":{"begin":869,"end":988},"obj":"Sentence"},{"id":"T10","span":{"begin":989,"end":1183},"obj":"Sentence"},{"id":"T11","span":{"begin":1184,"end":1420},"obj":"Sentence"}],"namespaces":[{"prefix":"_base","uri":"http://pubannotation.org/ontology/tao.owl#"}],"text":"Wwp2, an E3 ubiquitin ligase that targets transcription factor Oct-4 for ubiquitination.\nThe POU transcription factor Oct-4 is a master regulator affecting the fate of pluripotent embryonic stem cells. However, the precise mechanisms by which the activation and expression of Oct-4 are regulated still remain to be elucidated. We describe here a novel murine ubiquitin ligase, Wwp2, that specifically interacts with Oct-4 and promotes its ubiquitination both in vivo and in vitro. Remarkably, the expression of a catalytically inactive point mutant of Wwp2 abolishes Oct-4 ubiquitination. Moreover, Wwp2 promotes Oct-4 degradation in the presence of overexpressed ubiquitin. The degradation is blocked by treatment with proteasome inhibitor. Fusion of a single ubiquitin to Oct-4 inactivates its transcriptional activity in a heterologous Oct-4-driven reporter system. Furthermore, overexpression of Wwp2 in embryonic stem cells significantly reduces the Oct-4-transcriptional activities. Collectively, we demonstrate for the first time that Oct-4 can be post-translationally modified by ubiquitination and that this modification dramatically suppresses its transcriptional activity. These results reveal that the functional status of Oct-4, in addition to its expression level, dictates its transcriptional activity, and the results open up a new avenue to understand how Oct-4 defines the fate of embryonic stem cells."}

{"project":"Glycosmos6-MAT","denotations":[{"id":"T1","span":{"begin":190,"end":200},"obj":"http://purl.obolibrary.org/obo/MAT_0000185"},{"id":"T2","span":{"begin":190,"end":194},"obj":"http://purl.obolibrary.org/obo/MAT_0000239"},{"id":"T3","span":{"begin":918,"end":928},"obj":"http://purl.obolibrary.org/obo/MAT_0000185"},{"id":"T4","span":{"begin":918,"end":922},"obj":"http://purl.obolibrary.org/obo/MAT_0000239"},{"id":"T5","span":{"begin":1409,"end":1419},"obj":"http://purl.obolibrary.org/obo/MAT_0000185"},{"id":"T6","span":{"begin":1409,"end":1413},"obj":"http://purl.obolibrary.org/obo/MAT_0000239"}],"text":"Wwp2, an E3 ubiquitin ligase that targets transcription factor Oct-4 for ubiquitination.\nThe POU transcription factor Oct-4 is a master regulator affecting the fate of pluripotent embryonic stem cells. However, the precise mechanisms by which the activation and expression of Oct-4 are regulated still remain to be elucidated. We describe here a novel murine ubiquitin ligase, Wwp2, that specifically interacts with Oct-4 and promotes its ubiquitination both in vivo and in vitro. Remarkably, the expression of a catalytically inactive point mutant of Wwp2 abolishes Oct-4 ubiquitination. Moreover, Wwp2 promotes Oct-4 degradation in the presence of overexpressed ubiquitin. The degradation is blocked by treatment with proteasome inhibitor. Fusion of a single ubiquitin to Oct-4 inactivates its transcriptional activity in a heterologous Oct-4-driven reporter system. Furthermore, overexpression of Wwp2 in embryonic stem cells significantly reduces the Oct-4-transcriptional activities. Collectively, we demonstrate for the first time that Oct-4 can be post-translationally modified by ubiquitination and that this modification dramatically suppresses its transcriptional activity. These results reveal that the functional status of Oct-4, in addition to its expression level, dictates its transcriptional activity, and the results open up a new avenue to understand how Oct-4 defines the fate of embryonic stem cells."}

{"project":"2015-BEL-Sample","denotations":[{"id":"T1","span":{"begin":327,"end":479},"obj":"complex(p(MGI:Wwp2),p(MGI:Pou5f1)) directlyIncreases deg(p(MGI:Pou5f1))"}],"text":"Wwp2, an E3 ubiquitin ligase that targets transcription factor Oct-4 for ubiquitination.\nThe POU transcription factor Oct-4 is a master regulator affecting the fate of pluripotent embryonic stem cells. However, the precise mechanisms by which the activation and expression of Oct-4 are regulated still remain to be elucidated. We describe here a novel murine ubiquitin ligase, Wwp2, that specifically interacts with Oct-4 and promotes its ubiquitination both in vivo and in vitro. Remarkably, the expression of a catalytically inactive point mutant of Wwp2 abolishes Oct-4 ubiquitination. Moreover, Wwp2 promotes Oct-4 degradation in the presence of overexpressed ubiquitin. The degradation is blocked by treatment with proteasome inhibitor. Fusion of a single ubiquitin to Oct-4 inactivates its transcriptional activity in a heterologous Oct-4-driven reporter system. Furthermore, overexpression of Wwp2 in embryonic stem cells significantly reduces the Oct-4-transcriptional activities. Collectively, we demonstrate for the first time that Oct-4 can be post-translationally modified by ubiquitination and that this modification dramatically suppresses its transcriptional activity. These results reveal that the functional status of Oct-4, in addition to its expression level, dictates its transcriptional activity, and the results open up a new avenue to understand how Oct-4 defines the fate of embryonic stem cells."}

{"project":"2015-BEL-Sample-2","denotations":[{"id":"BEL:20000540","span":{"begin":327,"end":479},"obj":"complex(p(MGI:Wwp2),p(MGI:Pou5f1)) directlyIncreases deg(p(MGI:Pou5f1))"},{"id":"BEL:20033314","span":{"begin":327,"end":479},"obj":"cat(p(MGI:Wwp2)) directlyIncreases deg(p(MGI:Pou5f1))"},{"id":"BEL:20035050","span":{"begin":327,"end":479},"obj":"complex(p(MGI:Wwp2),p(MGI:Pou5f1)) directlyIncreases deg(p(MGI:Pou5f1))"}],"text":"Wwp2, an E3 ubiquitin ligase that targets transcription factor Oct-4 for ubiquitination.\nThe POU transcription factor Oct-4 is a master regulator affecting the fate of pluripotent embryonic stem cells. However, the precise mechanisms by which the activation and expression of Oct-4 are regulated still remain to be elucidated. We describe here a novel murine ubiquitin ligase, Wwp2, that specifically interacts with Oct-4 and promotes its ubiquitination both in vivo and in vitro. Remarkably, the expression of a catalytically inactive point mutant of Wwp2 abolishes Oct-4 ubiquitination. Moreover, Wwp2 promotes Oct-4 degradation in the presence of overexpressed ubiquitin. The degradation is blocked by treatment with proteasome inhibitor. Fusion of a single ubiquitin to Oct-4 inactivates its transcriptional activity in a heterologous Oct-4-driven reporter system. Furthermore, overexpression of Wwp2 in embryonic stem cells significantly reduces the Oct-4-transcriptional activities. Collectively, we demonstrate for the first time that Oct-4 can be post-translationally modified by ubiquitination and that this modification dramatically suppresses its transcriptional activity. These results reveal that the functional status of Oct-4, in addition to its expression level, dictates its transcriptional activity, and the results open up a new avenue to understand how Oct-4 defines the fate of embryonic stem cells."}

{"project":"Anatomy-MAT","denotations":[{"id":"T1","span":{"begin":190,"end":200},"obj":"Body_part"},{"id":"T2","span":{"begin":918,"end":928},"obj":"Body_part"},{"id":"T3","span":{"begin":1409,"end":1419},"obj":"Body_part"}],"attributes":[{"id":"A1","pred":"mat_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/MAT_0000185"},{"id":"A2","pred":"mat_id","subj":"T2","obj":"http://purl.obolibrary.org/obo/MAT_0000185"},{"id":"A3","pred":"mat_id","subj":"T3","obj":"http://purl.obolibrary.org/obo/MAT_0000185"}],"text":"Wwp2, an E3 ubiquitin ligase that targets transcription factor Oct-4 for ubiquitination.\nThe POU transcription factor Oct-4 is a master regulator affecting the fate of pluripotent embryonic stem cells. However, the precise mechanisms by which the activation and expression of Oct-4 are regulated still remain to be elucidated. We describe here a novel murine ubiquitin ligase, Wwp2, that specifically interacts with Oct-4 and promotes its ubiquitination both in vivo and in vitro. Remarkably, the expression of a catalytically inactive point mutant of Wwp2 abolishes Oct-4 ubiquitination. Moreover, Wwp2 promotes Oct-4 degradation in the presence of overexpressed ubiquitin. The degradation is blocked by treatment with proteasome inhibitor. Fusion of a single ubiquitin to Oct-4 inactivates its transcriptional activity in a heterologous Oct-4-driven reporter system. Furthermore, overexpression of Wwp2 in embryonic stem cells significantly reduces the Oct-4-transcriptional activities. Collectively, we demonstrate for the first time that Oct-4 can be post-translationally modified by ubiquitination and that this modification dramatically suppresses its transcriptional activity. These results reveal that the functional status of Oct-4, in addition to its expression level, dictates its transcriptional activity, and the results open up a new avenue to understand how Oct-4 defines the fate of embryonic stem cells."}

{"project":"Anatomy-UBERON","denotations":[{"id":"T1","span":{"begin":190,"end":200},"obj":"Body_part"},{"id":"T2","span":{"begin":918,"end":928},"obj":"Body_part"},{"id":"T3","span":{"begin":1409,"end":1419},"obj":"Body_part"}],"attributes":[{"id":"A1","pred":"uberon_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/CL_0000034"},{"id":"A2","pred":"uberon_id","subj":"T2","obj":"http://purl.obolibrary.org/obo/CL_0000034"},{"id":"A3","pred":"uberon_id","subj":"T3","obj":"http://purl.obolibrary.org/obo/CL_0000034"}],"text":"Wwp2, an E3 ubiquitin ligase that targets transcription factor Oct-4 for ubiquitination.\nThe POU transcription factor Oct-4 is a master regulator affecting the fate of pluripotent embryonic stem cells. However, the precise mechanisms by which the activation and expression of Oct-4 are regulated still remain to be elucidated. We describe here a novel murine ubiquitin ligase, Wwp2, that specifically interacts with Oct-4 and promotes its ubiquitination both in vivo and in vitro. Remarkably, the expression of a catalytically inactive point mutant of Wwp2 abolishes Oct-4 ubiquitination. Moreover, Wwp2 promotes Oct-4 degradation in the presence of overexpressed ubiquitin. The degradation is blocked by treatment with proteasome inhibitor. Fusion of a single ubiquitin to Oct-4 inactivates its transcriptional activity in a heterologous Oct-4-driven reporter system. Furthermore, overexpression of Wwp2 in embryonic stem cells significantly reduces the Oct-4-transcriptional activities. Collectively, we demonstrate for the first time that Oct-4 can be post-translationally modified by ubiquitination and that this modification dramatically suppresses its transcriptional activity. These results reveal that the functional status of Oct-4, in addition to its expression level, dictates its transcriptional activity, and the results open up a new avenue to understand how Oct-4 defines the fate of embryonic stem cells."}

{"project":"CL-cell","denotations":[{"id":"T1","span":{"begin":180,"end":200},"obj":"Cell"},{"id":"T2","span":{"begin":908,"end":928},"obj":"Cell"},{"id":"T3","span":{"begin":1399,"end":1419},"obj":"Cell"}],"attributes":[{"id":"A1","pred":"cl_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/CL:0002322"},{"id":"A2","pred":"cl_id","subj":"T2","obj":"http://purl.obolibrary.org/obo/CL:0002322"},{"id":"A3","pred":"cl_id","subj":"T3","obj":"http://purl.obolibrary.org/obo/CL:0002322"}],"text":"Wwp2, an E3 ubiquitin ligase that targets transcription factor Oct-4 for ubiquitination.\nThe POU transcription factor Oct-4 is a master regulator affecting the fate of pluripotent embryonic stem cells. However, the precise mechanisms by which the activation and expression of Oct-4 are regulated still remain to be elucidated. We describe here a novel murine ubiquitin ligase, Wwp2, that specifically interacts with Oct-4 and promotes its ubiquitination both in vivo and in vitro. Remarkably, the expression of a catalytically inactive point mutant of Wwp2 abolishes Oct-4 ubiquitination. Moreover, Wwp2 promotes Oct-4 degradation in the presence of overexpressed ubiquitin. The degradation is blocked by treatment with proteasome inhibitor. Fusion of a single ubiquitin to Oct-4 inactivates its transcriptional activity in a heterologous Oct-4-driven reporter system. Furthermore, overexpression of Wwp2 in embryonic stem cells significantly reduces the Oct-4-transcriptional activities. Collectively, we demonstrate for the first time that Oct-4 can be post-translationally modified by ubiquitination and that this modification dramatically suppresses its transcriptional activity. These results reveal that the functional status of Oct-4, in addition to its expression level, dictates its transcriptional activity, and the results open up a new avenue to understand how Oct-4 defines the fate of embryonic stem cells."}