PubMed:12417738 JSONTXT

{"project":"FSU-PRGE","denotations":[{"id":"T1","span":{"begin":26,"end":30},"obj":"protein"},{"id":"T2","span":{"begin":100,"end":104},"obj":"protein"},{"id":"T3","span":{"begin":224,"end":228},"obj":"protein"},{"id":"T4","span":{"begin":232,"end":236},"obj":"protein"},{"id":"T5","span":{"begin":237,"end":243},"obj":"protein"},{"id":"T6","span":{"begin":258,"end":275},"obj":"protein"},{"id":"T7","span":{"begin":304,"end":308},"obj":"protein"},{"id":"T8","span":{"begin":357,"end":361},"obj":"protein"},{"id":"T9","span":{"begin":379,"end":383},"obj":"protein"},{"id":"T10","span":{"begin":425,"end":429},"obj":"protein"},{"id":"T11","span":{"begin":457,"end":461},"obj":"protein"},{"id":"T12","span":{"begin":497,"end":501},"obj":"protein"},{"id":"T13","span":{"begin":642,"end":646},"obj":"protein"},{"id":"T14","span":{"begin":771,"end":775},"obj":"protein"},{"id":"T15","span":{"begin":812,"end":816},"obj":"protein"},{"id":"T16","span":{"begin":823,"end":827},"obj":"protein"},{"id":"T17","span":{"begin":875,"end":879},"obj":"protein"},{"id":"T18","span":{"begin":930,"end":934},"obj":"protein"},{"id":"T19","span":{"begin":948,"end":952},"obj":"protein"},{"id":"T20","span":{"begin":1030,"end":1035},"obj":"protein"},{"id":"T21","span":{"begin":1054,"end":1059},"obj":"protein"},{"id":"T22","span":{"begin":1120,"end":1124},"obj":"protein"},{"id":"T23","span":{"begin":1347,"end":1351},"obj":"protein"}],"text":"In vivo interference with Skp1 function leads to genetic instability and neoplastic transformation.\nSkp1 is involved in a variety of crucial cellular functions, among which the best understood is the formation together with Cul1 of Skp1-cullin-F-box protein ubiquitin ligases. To investigate the role of Skp1, we generated transgenic (Tg) mice expressing a Cul1 deletion mutant (Cul1-N252) able to sequestrate and inactivate Skp1. In vivo interference with Skp1 function through expression of the Cul1-N252 mutant into the T-cell lineage results in lymphoid organ hypoplasia and reduced proliferation. Nonetheless, after a period of latency, Cul1-N252 Tg mice succumb to T-cell lymphomas with high penetrance (\u003e80%). Both T-cell depletion and the neoplastic phenotype of Cul1-N252 Tg mice are largely rescued in Cul1-N252, Skp1 double-Tg mice, indicating that the effects of Cul1-N252 are due to a sequestration of the endogenous Skp1. Analysis of Cul1-N252 lymphomas demonstrates striking karyotype heterogeneity associated with c-myc amplification and c-Myc overexpression. We show that the in vitro expression of the Cul1-N252 mutant causes a pleiotrophic phenotype, which includes the formation of multinucleated cells, centrosome and mitotic spindle abnormalities, and impaired chromosome segregation. Our findings support a crucial role for Skp1 in proper chromosomal segregation, which is required for the maintenance of euploidy and suppression of transformation."}

{"project":"PIR-corpus2","denotations":[{"id":"T1","span":{"begin":26,"end":30},"obj":"protein"},{"id":"T2","span":{"begin":100,"end":104},"obj":"protein"},{"id":"T3","span":{"begin":224,"end":228},"obj":"protein"},{"id":"T4","span":{"begin":232,"end":275},"obj":"protein"},{"id":"T5","span":{"begin":304,"end":308},"obj":"protein"},{"id":"T6","span":{"begin":357,"end":361},"obj":"protein"},{"id":"T7","span":{"begin":379,"end":383},"obj":"protein"},{"id":"T8","span":{"begin":425,"end":429},"obj":"protein"},{"id":"T9","span":{"begin":457,"end":461},"obj":"protein"},{"id":"T10","span":{"begin":497,"end":501},"obj":"protein"},{"id":"T11","span":{"begin":642,"end":646},"obj":"protein"},{"id":"T12","span":{"begin":771,"end":775},"obj":"protein"},{"id":"T13","span":{"begin":812,"end":816},"obj":"protein"},{"id":"T14","span":{"begin":823,"end":827},"obj":"protein"},{"id":"T15","span":{"begin":875,"end":879},"obj":"protein"},{"id":"T16","span":{"begin":930,"end":934},"obj":"protein"},{"id":"T17","span":{"begin":948,"end":952},"obj":"protein"},{"id":"T18","span":{"begin":1030,"end":1035},"obj":"protein"},{"id":"T19","span":{"begin":1054,"end":1059},"obj":"protein"},{"id":"T20","span":{"begin":1120,"end":1124},"obj":"protein"},{"id":"T21","span":{"begin":1347,"end":1351},"obj":"protein"}],"text":"In vivo interference with Skp1 function leads to genetic instability and neoplastic transformation.\nSkp1 is involved in a variety of crucial cellular functions, among which the best understood is the formation together with Cul1 of Skp1-cullin-F-box protein ubiquitin ligases. To investigate the role of Skp1, we generated transgenic (Tg) mice expressing a Cul1 deletion mutant (Cul1-N252) able to sequestrate and inactivate Skp1. In vivo interference with Skp1 function through expression of the Cul1-N252 mutant into the T-cell lineage results in lymphoid organ hypoplasia and reduced proliferation. Nonetheless, after a period of latency, Cul1-N252 Tg mice succumb to T-cell lymphomas with high penetrance (\u003e80%). Both T-cell depletion and the neoplastic phenotype of Cul1-N252 Tg mice are largely rescued in Cul1-N252, Skp1 double-Tg mice, indicating that the effects of Cul1-N252 are due to a sequestration of the endogenous Skp1. Analysis of Cul1-N252 lymphomas demonstrates striking karyotype heterogeneity associated with c-myc amplification and c-Myc overexpression. We show that the in vitro expression of the Cul1-N252 mutant causes a pleiotrophic phenotype, which includes the formation of multinucleated cells, centrosome and mitotic spindle abnormalities, and impaired chromosome segregation. Our findings support a crucial role for Skp1 in proper chromosomal segregation, which is required for the maintenance of euploidy and suppression of transformation."}

{"project":"DisGeNET5_gene_disease","denotations":[{"id":"12417738-4#40#44#gene8454","span":{"begin":642,"end":646},"obj":"gene8454"},{"id":"12417738-4#69#85#diseaseC0079772","span":{"begin":671,"end":687},"obj":"diseaseC0079772"},{"id":"12417738-6#12#16#gene8454","span":{"begin":948,"end":952},"obj":"gene8454"},{"id":"12417738-6#22#31#diseaseC0024299","span":{"begin":958,"end":967},"obj":"diseaseC0024299"}],"relations":[{"id":"40#44#gene845469#85#diseaseC0079772","pred":"associated_with","subj":"12417738-4#40#44#gene8454","obj":"12417738-4#69#85#diseaseC0079772"},{"id":"12#16#gene845422#31#diseaseC0024299","pred":"associated_with","subj":"12417738-6#12#16#gene8454","obj":"12417738-6#22#31#diseaseC0024299"}],"text":"In vivo interference with Skp1 function leads to genetic instability and neoplastic transformation.\nSkp1 is involved in a variety of crucial cellular functions, among which the best understood is the formation together with Cul1 of Skp1-cullin-F-box protein ubiquitin ligases. To investigate the role of Skp1, we generated transgenic (Tg) mice expressing a Cul1 deletion mutant (Cul1-N252) able to sequestrate and inactivate Skp1. In vivo interference with Skp1 function through expression of the Cul1-N252 mutant into the T-cell lineage results in lymphoid organ hypoplasia and reduced proliferation. Nonetheless, after a period of latency, Cul1-N252 Tg mice succumb to T-cell lymphomas with high penetrance (\u003e80%). Both T-cell depletion and the neoplastic phenotype of Cul1-N252 Tg mice are largely rescued in Cul1-N252, Skp1 double-Tg mice, indicating that the effects of Cul1-N252 are due to a sequestration of the endogenous Skp1. Analysis of Cul1-N252 lymphomas demonstrates striking karyotype heterogeneity associated with c-myc amplification and c-Myc overexpression. We show that the in vitro expression of the Cul1-N252 mutant causes a pleiotrophic phenotype, which includes the formation of multinucleated cells, centrosome and mitotic spindle abnormalities, and impaired chromosome segregation. Our findings support a crucial role for Skp1 in proper chromosomal segregation, which is required for the maintenance of euploidy and suppression of transformation."}

{"project":"PIR-corpus1","denotations":[{"id":"T1","span":{"begin":26,"end":30},"obj":"protein"},{"id":"T2","span":{"begin":100,"end":104},"obj":"protein"},{"id":"T3","span":{"begin":224,"end":228},"obj":"protein"},{"id":"T4","span":{"begin":232,"end":275},"obj":"protein"},{"id":"T5","span":{"begin":304,"end":308},"obj":"protein"},{"id":"T6","span":{"begin":357,"end":377},"obj":"protein"},{"id":"T7","span":{"begin":379,"end":388},"obj":"protein"},{"id":"T8","span":{"begin":425,"end":429},"obj":"protein"},{"id":"T9","span":{"begin":457,"end":461},"obj":"protein"},{"id":"T10","span":{"begin":875,"end":884},"obj":"protein"},{"id":"T11","span":{"begin":930,"end":934},"obj":"protein"},{"id":"T12","span":{"begin":1054,"end":1059},"obj":"protein"},{"id":"T13","span":{"begin":1120,"end":1136},"obj":"protein"},{"id":"T14","span":{"begin":1347,"end":1351},"obj":"protein"}],"text":"In vivo interference with Skp1 function leads to genetic instability and neoplastic transformation.\nSkp1 is involved in a variety of crucial cellular functions, among which the best understood is the formation together with Cul1 of Skp1-cullin-F-box protein ubiquitin ligases. To investigate the role of Skp1, we generated transgenic (Tg) mice expressing a Cul1 deletion mutant (Cul1-N252) able to sequestrate and inactivate Skp1. In vivo interference with Skp1 function through expression of the Cul1-N252 mutant into the T-cell lineage results in lymphoid organ hypoplasia and reduced proliferation. Nonetheless, after a period of latency, Cul1-N252 Tg mice succumb to T-cell lymphomas with high penetrance (\u003e80%). Both T-cell depletion and the neoplastic phenotype of Cul1-N252 Tg mice are largely rescued in Cul1-N252, Skp1 double-Tg mice, indicating that the effects of Cul1-N252 are due to a sequestration of the endogenous Skp1. Analysis of Cul1-N252 lymphomas demonstrates striking karyotype heterogeneity associated with c-myc amplification and c-Myc overexpression. We show that the in vitro expression of the Cul1-N252 mutant causes a pleiotrophic phenotype, which includes the formation of multinucleated cells, centrosome and mitotic spindle abnormalities, and impaired chromosome segregation. Our findings support a crucial role for Skp1 in proper chromosomal segregation, which is required for the maintenance of euploidy and suppression of transformation."}

{"project":"DisGeNET","denotations":[{"id":"T0","span":{"begin":948,"end":952},"obj":"gene:8454"},{"id":"T1","span":{"begin":958,"end":967},"obj":"disease:C0024299"}],"relations":[{"id":"R1","pred":"associated_with","subj":"T0","obj":"T1"}],"namespaces":[{"prefix":"gene","uri":"http://www.ncbi.nlm.nih.gov/gene/"},{"prefix":"disease","uri":"http://purl.bioontology.org/ontology/MEDLINEPLUS/"}],"text":"In vivo interference with Skp1 function leads to genetic instability and neoplastic transformation.\nSkp1 is involved in a variety of crucial cellular functions, among which the best understood is the formation together with Cul1 of Skp1-cullin-F-box protein ubiquitin ligases. To investigate the role of Skp1, we generated transgenic (Tg) mice expressing a Cul1 deletion mutant (Cul1-N252) able to sequestrate and inactivate Skp1. In vivo interference with Skp1 function through expression of the Cul1-N252 mutant into the T-cell lineage results in lymphoid organ hypoplasia and reduced proliferation. Nonetheless, after a period of latency, Cul1-N252 Tg mice succumb to T-cell lymphomas with high penetrance (\u003e80%). Both T-cell depletion and the neoplastic phenotype of Cul1-N252 Tg mice are largely rescued in Cul1-N252, Skp1 double-Tg mice, indicating that the effects of Cul1-N252 are due to a sequestration of the endogenous Skp1. Analysis of Cul1-N252 lymphomas demonstrates striking karyotype heterogeneity associated with c-myc amplification and c-Myc overexpression. We show that the in vitro expression of the Cul1-N252 mutant causes a pleiotrophic phenotype, which includes the formation of multinucleated cells, centrosome and mitotic spindle abnormalities, and impaired chromosome segregation. Our findings support a crucial role for Skp1 in proper chromosomal segregation, which is required for the maintenance of euploidy and suppression of transformation."}