PubMed:28481876 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PubMed/sourceid/28481876","sourcedb":"PubMed","sourceid":"28481876","text":"Oncogenic activity of amplified miniature chromosome maintenance 8 in human malignancies.\nMiniature chromosome maintenance (MCM) proteins play critical roles in DNA replication licensing, initiation and elongation. MCM8, one of the MCM proteins playing a critical role in DNA repairing and recombination, was found to have overexpression and increased DNA copy number in a variety of human malignancies. The gain of MCM8 is associated with aggressive clinical features of several human cancers. Increased expression of MCM8 in prostate cancer is associated with cancer recurrence. Forced expression of MCM8 in RWPE1 cells, the immortalized but non-transformed prostate epithelial cell line, exhibited fast cell growth and transformation, while knock down of MCM8 in PC3, DU145 and LNCaP cells induced cell growth arrest, and decreased tumour volumes and mortality of severe combined immunodeficiency mice xenografted with PC3 and DU145 cells. MCM8 bound cyclin D1 and activated Rb protein phosphorylation by cyclin-dependent kinase 4 in vitro and in vivo. The cyclin D1/MCM8 interaction is required for Rb phosphorylation and S-phase entry in cancer cells. As a result, our study showed that copy number increase and overexpression of MCM8 may play critical roles in human cancer development.","tracks":[{"project":"TEST-CellLine","denotations":[{"id":"T1","span":{"begin":610,"end":615},"obj":"CellLine"},{"id":"T2","span":{"begin":766,"end":769},"obj":"CellLine"},{"id":"T5","span":{"begin":771,"end":776},"obj":"CellLine"},{"id":"T6","span":{"begin":781,"end":786},"obj":"CellLine"},{"id":"T7","span":{"begin":922,"end":925},"obj":"CellLine"},{"id":"T10","span":{"begin":930,"end":935},"obj":"CellLine"}],"attributes":[{"id":"A1","pred":"cellosaurus_accession_id","subj":"T1","obj":"CVCL_3791"},{"id":"A2","pred":"cellosaurus_accession_id","subj":"T2","obj":"CVCL_0035"},{"id":"A3","pred":"cellosaurus_accession_id","subj":"T2","obj":"CVCL_4055"},{"id":"A4","pred":"cellosaurus_accession_id","subj":"T2","obj":"CVCL_S982"},{"id":"A5","pred":"cellosaurus_accession_id","subj":"T5","obj":"CVCL_0105"},{"id":"A6","pred":"cellosaurus_accession_id","subj":"T6","obj":"CVCL_0395"},{"id":"A7","pred":"cellosaurus_accession_id","subj":"T7","obj":"CVCL_0035"},{"id":"A8","pred":"cellosaurus_accession_id","subj":"T7","obj":"CVCL_4055"},{"id":"A9","pred":"cellosaurus_accession_id","subj":"T7","obj":"CVCL_S982"},{"id":"A10","pred":"cellosaurus_accession_id","subj":"T10","obj":"CVCL_0105"},{"subj":"T1","pred":"source","obj":"TEST-CellLine"},{"subj":"T2","pred":"source","obj":"TEST-CellLine"},{"subj":"T5","pred":"source","obj":"TEST-CellLine"},{"subj":"T6","pred":"source","obj":"TEST-CellLine"},{"subj":"T7","pred":"source","obj":"TEST-CellLine"},{"subj":"T10","pred":"source","obj":"TEST-CellLine"}]},{"project":"TEST-DiseaseOrPhenotypicFeature","denotations":[{"id":"T1","span":{"begin":76,"end":88},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T2","span":{"begin":390,"end":402},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T3","span":{"begin":486,"end":493},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T4","span":{"begin":527,"end":542},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T5","span":{"begin":562,"end":568},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T6","span":{"begin":835,"end":841},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T7","span":{"begin":867,"end":899},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T8","span":{"begin":1143,"end":1149},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T9","span":{"begin":1273,"end":1279},"obj":"DiseaseOrPhenotypicFeature"}],"attributes":[{"id":"A1","pred":"#label","subj":"T1","obj":"D009369"},{"id":"A3","pred":"#label","subj":"T3","obj":"D009369"},{"id":"A9","pred":"#label","subj":"T9","obj":"D009369"},{"id":"A2","pred":"#label","subj":"T2","obj":"D009369"},{"id":"A4","pred":"#label","subj":"T4","obj":"D011471"},{"id":"A6","pred":"#label","subj":"T6","obj":"DISEASE"},{"id":"A8","pred":"#label","subj":"T8","obj":"D009369"},{"id":"A7","pred":"#label","subj":"T7","obj":"D016511"},{"id":"A5","pred":"#label","subj":"T5","obj":"D009369"},{"subj":"T1","pred":"source","obj":"TEST-DiseaseOrPhenotypicFeature"},{"subj":"T2","pred":"source","obj":"TEST-DiseaseOrPhenotypicFeature"},{"subj":"T3","pred":"source","obj":"TEST-DiseaseOrPhenotypicFeature"},{"subj":"T4","pred":"source","obj":"TEST-DiseaseOrPhenotypicFeature"},{"subj":"T5","pred":"source","obj":"TEST-DiseaseOrPhenotypicFeature"},{"subj":"T6","pred":"source","obj":"TEST-DiseaseOrPhenotypicFeature"},{"subj":"T7","pred":"source","obj":"TEST-DiseaseOrPhenotypicFeature"},{"subj":"T8","pred":"source","obj":"TEST-DiseaseOrPhenotypicFeature"},{"subj":"T9","pred":"source","obj":"TEST-DiseaseOrPhenotypicFeature"}]},{"project":"TEST-OrganismTaxon","denotations":[{"id":"T1","span":{"begin":70,"end":75},"obj":"OrganismTaxon"},{"id":"T2","span":{"begin":384,"end":389},"obj":"OrganismTaxon"},{"id":"T3","span":{"begin":480,"end":485},"obj":"OrganismTaxon"},{"id":"T4","span":{"begin":900,"end":904},"obj":"OrganismTaxon"},{"id":"T5","span":{"begin":1267,"end":1272},"obj":"OrganismTaxon"}],"attributes":[{"subj":"T1","pred":"source","obj":"TEST-OrganismTaxon"},{"subj":"T2","pred":"source","obj":"TEST-OrganismTaxon"},{"subj":"T3","pred":"source","obj":"TEST-OrganismTaxon"},{"subj":"T4","pred":"source","obj":"TEST-OrganismTaxon"},{"subj":"T5","pred":"source","obj":"TEST-OrganismTaxon"}]},{"project":"Test-GeneOrGeneProduct","denotations":[{"id":"T1","span":{"begin":32,"end":41},"obj":"GeneOrGeneProduct"},{"id":"T2","span":{"begin":90,"end":99},"obj":"GeneOrGeneProduct"},{"id":"T3","span":{"begin":161,"end":176},"obj":"GeneOrGeneProduct"},{"id":"T4","span":{"begin":215,"end":219},"obj":"GeneOrGeneProduct"},{"id":"T5","span":{"begin":416,"end":420},"obj":"GeneOrGeneProduct"},{"id":"T6","span":{"begin":519,"end":523},"obj":"GeneOrGeneProduct"},{"id":"T7","span":{"begin":602,"end":606},"obj":"GeneOrGeneProduct"},{"id":"T8","span":{"begin":758,"end":762},"obj":"GeneOrGeneProduct"},{"id":"T9","span":{"begin":943,"end":947},"obj":"GeneOrGeneProduct"},{"id":"T10","span":{"begin":954,"end":963},"obj":"GeneOrGeneProduct"},{"id":"T11","span":{"begin":1008,"end":1033},"obj":"GeneOrGeneProduct"},{"id":"T12","span":{"begin":1060,"end":1069},"obj":"GeneOrGeneProduct"},{"id":"T13","span":{"begin":1070,"end":1074},"obj":"GeneOrGeneProduct"},{"id":"T14","span":{"begin":1235,"end":1239},"obj":"GeneOrGeneProduct"}],"attributes":[{"subj":"T1","pred":"source","obj":"Test-GeneOrGeneProduct"},{"subj":"T2","pred":"source","obj":"Test-GeneOrGeneProduct"},{"subj":"T3","pred":"source","obj":"Test-GeneOrGeneProduct"},{"subj":"T4","pred":"source","obj":"Test-GeneOrGeneProduct"},{"subj":"T5","pred":"source","obj":"Test-GeneOrGeneProduct"},{"subj":"T6","pred":"source","obj":"Test-GeneOrGeneProduct"},{"subj":"T7","pred":"source","obj":"Test-GeneOrGeneProduct"},{"subj":"T8","pred":"source","obj":"Test-GeneOrGeneProduct"},{"subj":"T9","pred":"source","obj":"Test-GeneOrGeneProduct"},{"subj":"T10","pred":"source","obj":"Test-GeneOrGeneProduct"},{"subj":"T11","pred":"source","obj":"Test-GeneOrGeneProduct"},{"subj":"T12","pred":"source","obj":"Test-GeneOrGeneProduct"},{"subj":"T13","pred":"source","obj":"Test-GeneOrGeneProduct"},{"subj":"T14","pred":"source","obj":"Test-GeneOrGeneProduct"}]},{"project":"Test-merged-2","denotations":[{"id":"T88930","span":{"begin":610,"end":615},"obj":"CellLine"},{"id":"T19516","span":{"begin":766,"end":769},"obj":"CellLine"},{"id":"T7640","span":{"begin":771,"end":776},"obj":"CellLine"},{"id":"T88653","span":{"begin":781,"end":786},"obj":"CellLine"},{"id":"T1450","span":{"begin":922,"end":925},"obj":"CellLine"},{"id":"T15444","span":{"begin":930,"end":935},"obj":"CellLine"},{"id":"T59391","span":{"begin":32,"end":41},"obj":"GeneOrGeneProduct"},{"id":"T11462","span":{"begin":90,"end":99},"obj":"GeneOrGeneProduct"},{"id":"T82079","span":{"begin":161,"end":176},"obj":"GeneOrGeneProduct"},{"id":"T45817","span":{"begin":215,"end":219},"obj":"GeneOrGeneProduct"},{"id":"T50895","span":{"begin":416,"end":420},"obj":"GeneOrGeneProduct"},{"id":"T64477","span":{"begin":519,"end":523},"obj":"GeneOrGeneProduct"},{"id":"T66941","span":{"begin":602,"end":606},"obj":"GeneOrGeneProduct"},{"id":"T15652","span":{"begin":758,"end":762},"obj":"GeneOrGeneProduct"},{"id":"T10504","span":{"begin":943,"end":947},"obj":"GeneOrGeneProduct"},{"id":"T10","span":{"begin":954,"end":963},"obj":"GeneOrGeneProduct"},{"id":"T11","span":{"begin":1008,"end":1033},"obj":"GeneOrGeneProduct"},{"id":"T12","span":{"begin":1060,"end":1069},"obj":"GeneOrGeneProduct"},{"id":"T13","span":{"begin":1070,"end":1074},"obj":"GeneOrGeneProduct"},{"id":"T14","span":{"begin":1235,"end":1239},"obj":"GeneOrGeneProduct"},{"id":"T95892","span":{"begin":70,"end":75},"obj":"OrganismTaxon"},{"id":"T44422","span":{"begin":384,"end":389},"obj":"OrganismTaxon"},{"id":"T94609","span":{"begin":480,"end":485},"obj":"OrganismTaxon"},{"id":"T40471","span":{"begin":900,"end":904},"obj":"OrganismTaxon"},{"id":"T21907","span":{"begin":1267,"end":1272},"obj":"OrganismTaxon"},{"id":"T1","span":{"begin":76,"end":88},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T2","span":{"begin":390,"end":402},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T3","span":{"begin":486,"end":493},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T4","span":{"begin":527,"end":542},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T5","span":{"begin":562,"end":568},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T6","span":{"begin":835,"end":841},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T7","span":{"begin":867,"end":899},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T8","span":{"begin":1143,"end":1149},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T9","span":{"begin":1273,"end":1279},"obj":"DiseaseOrPhenotypicFeature"}],"attributes":[{"id":"A7","pred":"#label","subj":"T7","obj":"D016511"},{"id":"A9","pred":"#label","subj":"T9","obj":"D009369"},{"id":"A2","pred":"#label","subj":"T2","obj":"D009369"},{"id":"A5","pred":"#label","subj":"T5","obj":"D009369"},{"id":"A11758","pred":"cellosaurus_accession_id","subj":"T7640","obj":"CVCL_0105"},{"id":"A6","pred":"#label","subj":"T6","obj":"DISEASE"},{"id":"A10","pred":"cellosaurus_accession_id","subj":"T15444","obj":"CVCL_0105"},{"id":"A91936","pred":"cellosaurus_accession_id","subj":"T1450","obj":"CVCL_0035"},{"id":"A55930","pred":"cellosaurus_accession_id","subj":"T1450","obj":"CVCL_4055"},{"id":"A80222","pred":"cellosaurus_accession_id","subj":"T1450","obj":"CVCL_S982"},{"id":"A1","pred":"#label","subj":"T1","obj":"D009369"},{"id":"A8","pred":"#label","subj":"T8","obj":"D009369"},{"id":"A83441","pred":"cellosaurus_accession_id","subj":"T88653","obj":"CVCL_0395"},{"id":"A3","pred":"#label","subj":"T3","obj":"D009369"},{"id":"A4","pred":"#label","subj":"T4","obj":"D011471"},{"id":"A79690","pred":"cellosaurus_accession_id","subj":"T19516","obj":"CVCL_0035"},{"id":"A38060","pred":"cellosaurus_accession_id","subj":"T19516","obj":"CVCL_4055"},{"id":"A9600","pred":"cellosaurus_accession_id","subj":"T19516","obj":"CVCL_S982"},{"id":"A45105","pred":"cellosaurus_accession_id","subj":"T88930","obj":"CVCL_3791"},{"subj":"T88930","pred":"source","obj":"Test-merged-2"},{"subj":"T19516","pred":"source","obj":"Test-merged-2"},{"subj":"T7640","pred":"source","obj":"Test-merged-2"},{"subj":"T88653","pred":"source","obj":"Test-merged-2"},{"subj":"T1450","pred":"source","obj":"Test-merged-2"},{"subj":"T15444","pred":"source","obj":"Test-merged-2"},{"subj":"T59391","pred":"source","obj":"Test-merged-2"},{"subj":"T11462","pred":"source","obj":"Test-merged-2"},{"subj":"T82079","pred":"source","obj":"Test-merged-2"},{"subj":"T45817","pred":"source","obj":"Test-merged-2"},{"subj":"T50895","pred":"source","obj":"Test-merged-2"},{"subj":"T64477","pred":"source","obj":"Test-merged-2"},{"subj":"T66941","pred":"source","obj":"Test-merged-2"},{"subj":"T15652","pred":"source","obj":"Test-merged-2"},{"subj":"T10504","pred":"source","obj":"Test-merged-2"},{"subj":"T10","pred":"source","obj":"Test-merged-2"},{"subj":"T11","pred":"source","obj":"Test-merged-2"},{"subj":"T12","pred":"source","obj":"Test-merged-2"},{"subj":"T13","pred":"source","obj":"Test-merged-2"},{"subj":"T14","pred":"source","obj":"Test-merged-2"},{"subj":"T95892","pred":"source","obj":"Test-merged-2"},{"subj":"T44422","pred":"source","obj":"Test-merged-2"},{"subj":"T94609","pred":"source","obj":"Test-merged-2"},{"subj":"T40471","pred":"source","obj":"Test-merged-2"},{"subj":"T21907","pred":"source","obj":"Test-merged-2"},{"subj":"T1","pred":"source","obj":"Test-merged-2"},{"subj":"T2","pred":"source","obj":"Test-merged-2"},{"subj":"T3","pred":"source","obj":"Test-merged-2"},{"subj":"T4","pred":"source","obj":"Test-merged-2"},{"subj":"T5","pred":"source","obj":"Test-merged-2"},{"subj":"T6","pred":"source","obj":"Test-merged-2"},{"subj":"T7","pred":"source","obj":"Test-merged-2"},{"subj":"T8","pred":"source","obj":"Test-merged-2"},{"subj":"T9","pred":"source","obj":"Test-merged-2"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"TEST-CellLine","color":"#93b3ec","default":true},{"id":"TEST-DiseaseOrPhenotypicFeature","color":"#cdec93"},{"id":"TEST-OrganismTaxon","color":"#ec93e7"},{"id":"Test-GeneOrGeneProduct","color":"#93ecd7"},{"id":"Test-merged-2","color":"#ecbd93"}]}]}}