PubMed:25954247
Annnotations
{"target":"https://pubannotation.org/docs/sourcedb/PubMed/sourceid/25954247","sourcedb":"PubMed","sourceid":"25954247","source_url":"http://www.ncbi.nlm.nih.gov/pubmed/25954247","text":"Mutant p53 - Heat Shock Response Oncogenic Cooperation: A New Mechanism of Cancer Cell Survival.\nThe main tumor suppressor function of p53 as a \"guardian of the genome\" is to respond to cellular stress by transcriptional activation of apoptosis, growth arrest, or senescence in damaged cells. Not surprisingly, mutations in the p53 gene are the most frequent genetic alteration in human cancers. Importantly, mutant p53 (mutp53) proteins not only lose their wild-type tumor suppressor activity but also can actively promote tumor development. Two main mechanisms accounting for mutp53 proto-oncogenic activity are inhibition of the wild-type p53 in a dominant-negative fashion and gain of additional oncogenic activities known as gain-of-function (GOF). Here, we discuss a novel mechanism of mutp53 GOF, which relies on its oncogenic cooperation with the heat shock machinery. This coordinated adaptive mechanism renders cancer cells more resistant to proteotoxic stress and provides both, a strong survival advantage to cancer cells and a promising means for therapeutic intervention.","tracks":[{"project":"sonoma2","denotations":[{"id":"T0","span":{"begin":0,"end":6},"obj":"VAR"},{"id":"T1","span":{"begin":7,"end":10},"obj":"GENE"},{"id":"T2","span":{"begin":43,"end":54},"obj":"REG"},{"id":"T3","span":{"begin":75,"end":81},"obj":"DISEASE"},{"id":"T4","span":{"begin":87,"end":95},"obj":"CPA"},{"id":"T5","span":{"begin":106,"end":111},"obj":"DISEASE"},{"id":"T6","span":{"begin":135,"end":138},"obj":"GENE"},{"id":"T7","span":{"begin":221,"end":231},"obj":"POSREG"},{"id":"T8","span":{"begin":235,"end":244},"obj":"CPA"},{"id":"T9","span":{"begin":246,"end":259},"obj":"CPA"},{"id":"T10","span":{"begin":246,"end":259},"obj":"DISEASE"},{"id":"T11","span":{"begin":264,"end":274},"obj":"CPA"},{"id":"T12","span":{"begin":311,"end":320},"obj":"VAR"},{"id":"T13","span":{"begin":328,"end":331},"obj":"GENE"},{"id":"T14","span":{"begin":350,"end":358},"obj":"REG"},{"id":"T15","span":{"begin":367,"end":377},"obj":"VAR"},{"id":"T16","span":{"begin":387,"end":394},"obj":"DISEASE"},{"id":"T17","span":{"begin":409,"end":415},"obj":"VAR"},{"id":"T18","span":{"begin":416,"end":419},"obj":"GENE"},{"id":"T19","span":{"begin":421,"end":427},"obj":"GENE"},{"id":"T20","span":{"begin":429,"end":437},"obj":"GENE"},{"id":"T21","span":{"begin":447,"end":451},"obj":"NEGREG"},{"id":"T22","span":{"begin":468,"end":473},"obj":"DISEASE"},{"id":"T23","span":{"begin":474,"end":493},"obj":"MPA"},{"id":"T24","span":{"begin":516,"end":523},"obj":"POSREG"},{"id":"T25","span":{"begin":524,"end":529},"obj":"DISEASE"},{"id":"T26","span":{"begin":530,"end":541},"obj":"CPA"},{"id":"T27","span":{"begin":578,"end":584},"obj":"GENE"},{"id":"T28","span":{"begin":614,"end":624},"obj":"NEGREG"},{"id":"T29","span":{"begin":642,"end":645},"obj":"GENE"},{"id":"T30","span":{"begin":681,"end":685},"obj":"POSREG"},{"id":"T31","span":{"begin":792,"end":798},"obj":"GENE"},{"id":"T32","span":{"begin":921,"end":927},"obj":"DISEASE"},{"id":"T33","span":{"begin":934,"end":938},"obj":"POSREG"},{"id":"T34","span":{"begin":952,"end":970},"obj":"DISEASE"},{"id":"T35","span":{"begin":1008,"end":1017},"obj":"POSREG"},{"id":"T36","span":{"begin":1021,"end":1027},"obj":"DISEASE"}],"relations":[{"id":"R0","pred":"CauseOf","subj":"T0","obj":"T2"},{"id":"R1","pred":"CauseOf","subj":"T0","obj":"T4"},{"id":"R2","pred":"ThemeOf","subj":"T1","obj":"T0"},{"id":"R3","pred":"ThemeOf","subj":"T1","obj":"T2"},{"id":"R4","pred":"ThemeOf","subj":"T4","obj":"T2"},{"id":"R5","pred":"ThemeOf","subj":"T8","obj":"T7"},{"id":"R6","pred":"ThemeOf","subj":"T9","obj":"T7"},{"id":"R7","pred":"ThemeOf","subj":"T11","obj":"T7"},{"id":"R8","pred":"CauseOf","subj":"T12","obj":"T14"},{"id":"R9","pred":"ThemeOf","subj":"T13","obj":"T12"},{"id":"R10","pred":"ThemeOf","subj":"T13","obj":"T15"},{"id":"R11","pred":"CauseOf","subj":"T15","obj":"T14"},{"id":"R12","pred":"CauseOf","subj":"T17","obj":"T21"},{"id":"R13","pred":"CauseOf","subj":"T17","obj":"T24"},{"id":"R14","pred":"ThemeOf","subj":"T18","obj":"T17"},{"id":"R15","pred":"ThemeOf","subj":"T18","obj":"T20"},{"id":"R16","pred":"ThemeOf","subj":"T19","obj":"T17"},{"id":"R17","pred":"CauseOf","subj":"T19","obj":"T21"},{"id":"R18","pred":"ThemeOf","subj":"T23","obj":"T21"},{"id":"R19","pred":"ThemeOf","subj":"T26","obj":"T24"},{"id":"R20","pred":"CauseOf","subj":"T28","obj":"T30"},{"id":"R21","pred":"ThemeOf","subj":"T29","obj":"T28"}],"attributes":[{"subj":"T0","pred":"source","obj":"sonoma2"},{"subj":"T1","pred":"source","obj":"sonoma2"},{"subj":"T2","pred":"source","obj":"sonoma2"},{"subj":"T3","pred":"source","obj":"sonoma2"},{"subj":"T4","pred":"source","obj":"sonoma2"},{"subj":"T5","pred":"source","obj":"sonoma2"},{"subj":"T6","pred":"source","obj":"sonoma2"},{"subj":"T7","pred":"source","obj":"sonoma2"},{"subj":"T8","pred":"source","obj":"sonoma2"},{"subj":"T9","pred":"source","obj":"sonoma2"},{"subj":"T10","pred":"source","obj":"sonoma2"},{"subj":"T11","pred":"source","obj":"sonoma2"},{"subj":"T12","pred":"source","obj":"sonoma2"},{"subj":"T13","pred":"source","obj":"sonoma2"},{"subj":"T14","pred":"source","obj":"sonoma2"},{"subj":"T15","pred":"source","obj":"sonoma2"},{"subj":"T16","pred":"source","obj":"sonoma2"},{"subj":"T17","pred":"source","obj":"sonoma2"},{"subj":"T18","pred":"source","obj":"sonoma2"},{"subj":"T19","pred":"source","obj":"sonoma2"},{"subj":"T20","pred":"source","obj":"sonoma2"},{"subj":"T21","pred":"source","obj":"sonoma2"},{"subj":"T22","pred":"source","obj":"sonoma2"},{"subj":"T23","pred":"source","obj":"sonoma2"},{"subj":"T24","pred":"source","obj":"sonoma2"},{"subj":"T25","pred":"source","obj":"sonoma2"},{"subj":"T26","pred":"source","obj":"sonoma2"},{"subj":"T27","pred":"source","obj":"sonoma2"},{"subj":"T28","pred":"source","obj":"sonoma2"},{"subj":"T29","pred":"source","obj":"sonoma2"},{"subj":"T30","pred":"source","obj":"sonoma2"},{"subj":"T31","pred":"source","obj":"sonoma2"},{"subj":"T32","pred":"source","obj":"sonoma2"},{"subj":"T33","pred":"source","obj":"sonoma2"},{"subj":"T34","pred":"source","obj":"sonoma2"},{"subj":"T35","pred":"source","obj":"sonoma2"},{"subj":"T36","pred":"source","obj":"sonoma2"}]},{"project":"PubmedHPO","denotations":[{"id":"T1","span":{"begin":106,"end":111},"obj":"HP_0002664"},{"id":"T2","span":{"begin":387,"end":394},"obj":"HP_0002664"},{"id":"T3","span":{"begin":468,"end":473},"obj":"HP_0002664"},{"id":"T4","span":{"begin":524,"end":529},"obj":"HP_0002664"},{"id":"T5","span":{"begin":921,"end":927},"obj":"HP_0002664"},{"id":"T6","span":{"begin":1021,"end":1027},"obj":"HP_0002664"}],"attributes":[{"subj":"T1","pred":"source","obj":"PubmedHPO"},{"subj":"T2","pred":"source","obj":"PubmedHPO"},{"subj":"T3","pred":"source","obj":"PubmedHPO"},{"subj":"T4","pred":"source","obj":"PubmedHPO"},{"subj":"T5","pred":"source","obj":"PubmedHPO"},{"subj":"T6","pred":"source","obj":"PubmedHPO"}]},{"project":"kaiyin_test","denotations":[{"id":"T2","span":{"begin":409,"end":415},"obj":"Var"},{"id":"T1","span":{"begin":416,"end":419},"obj":"Gene"},{"id":"T3","span":{"begin":429,"end":437},"obj":"Protein"},{"id":"T4","span":{"begin":447,"end":451},"obj":"NegReg"},{"id":"T5","span":{"begin":468,"end":493},"obj":"CPA"},{"id":"T6","span":{"begin":507,"end":523},"obj":"PosReg"},{"id":"T7","span":{"begin":524,"end":541},"obj":"CPA"},{"id":"T8","span":{"begin":578,"end":584},"obj":"Var"},{"id":"T9","span":{"begin":681,"end":685},"obj":"PosReg"},{"id":"T10","span":{"begin":689,"end":720},"obj":"CPA"},{"id":"T13","span":{"begin":792,"end":798},"obj":"Var"},{"id":"T11","span":{"begin":934,"end":938},"obj":"PosReg"},{"id":"T12","span":{"begin":939,"end":970},"obj":"CPA"},{"id":"T14","span":{"begin":999,"end":1017},"obj":"CPA"}],"relations":[{"id":"R1","pred":"ThemeOf","subj":"T1","obj":"T3"},{"id":"R10","pred":"ThemeOf","subj":"T12","obj":"T11"},{"id":"R11","pred":"ThemeOf","subj":"T14","obj":"T11"},{"id":"R2","pred":"ThemeOf","subj":"T3","obj":"T2"},{"id":"R3","pred":"CauseOf","subj":"T2","obj":"T4"},{"id":"R4","pred":"ThemeOf","subj":"T5","obj":"T4"},{"id":"R5","pred":"CauseOf","subj":"T2","obj":"T6"},{"id":"R6","pred":"ThemeOf","subj":"T7","obj":"T6"},{"id":"R7","pred":"CauseOf","subj":"T8","obj":"T9"},{"id":"R8","pred":"ThemeOf","subj":"T10","obj":"T9"},{"id":"R9","pred":"CauseOf","subj":"T13","obj":"T11"}],"attributes":[{"subj":"T2","pred":"source","obj":"kaiyin_test"},{"subj":"T1","pred":"source","obj":"kaiyin_test"},{"subj":"T3","pred":"source","obj":"kaiyin_test"},{"subj":"T4","pred":"source","obj":"kaiyin_test"},{"subj":"T5","pred":"source","obj":"kaiyin_test"},{"subj":"T6","pred":"source","obj":"kaiyin_test"},{"subj":"T7","pred":"source","obj":"kaiyin_test"},{"subj":"T8","pred":"source","obj":"kaiyin_test"},{"subj":"T9","pred":"source","obj":"kaiyin_test"},{"subj":"T10","pred":"source","obj":"kaiyin_test"},{"subj":"T13","pred":"source","obj":"kaiyin_test"},{"subj":"T11","pred":"source","obj":"kaiyin_test"},{"subj":"T12","pred":"source","obj":"kaiyin_test"},{"subj":"T14","pred":"source","obj":"kaiyin_test"}]},{"project":"name_no","denotations":[{"id":"T2","span":{"begin":409,"end":415},"obj":"Var"},{"id":"T1","span":{"begin":416,"end":419},"obj":"Gene"},{"id":"T3","span":{"begin":429,"end":437},"obj":"Protein"},{"id":"T4","span":{"begin":447,"end":451},"obj":"NegReg"},{"id":"T5","span":{"begin":468,"end":493},"obj":"CPA"},{"id":"T6","span":{"begin":507,"end":523},"obj":"PosReg"},{"id":"T7","span":{"begin":524,"end":541},"obj":"CPA"},{"id":"T8","span":{"begin":578,"end":584},"obj":"Var"},{"id":"T9","span":{"begin":681,"end":685},"obj":"PosReg"},{"id":"T10","span":{"begin":689,"end":720},"obj":"CPA"},{"id":"T13","span":{"begin":792,"end":798},"obj":"Var"},{"id":"T11","span":{"begin":934,"end":938},"obj":"PosReg"},{"id":"T12","span":{"begin":939,"end":970},"obj":"CPA"},{"id":"T14","span":{"begin":999,"end":1017},"obj":"CPA"}],"relations":[{"id":"R1","pred":"ThemeOf","subj":"T1","obj":"T3"},{"id":"R10","pred":"ThemeOf","subj":"T12","obj":"T11"},{"id":"R11","pred":"ThemeOf","subj":"T14","obj":"T11"},{"id":"R2","pred":"ThemeOf","subj":"T3","obj":"T2"},{"id":"R3","pred":"CauseOf","subj":"T2","obj":"T4"},{"id":"R4","pred":"ThemeOf","subj":"T5","obj":"T4"},{"id":"R5","pred":"CauseOf","subj":"T2","obj":"T6"},{"id":"R6","pred":"ThemeOf","subj":"T7","obj":"T6"},{"id":"R7","pred":"CauseOf","subj":"T8","obj":"T9"},{"id":"R8","pred":"ThemeOf","subj":"T10","obj":"T9"},{"id":"R9","pred":"CauseOf","subj":"T13","obj":"T11"}],"attributes":[{"subj":"T2","pred":"source","obj":"name_no"},{"subj":"T1","pred":"source","obj":"name_no"},{"subj":"T3","pred":"source","obj":"name_no"},{"subj":"T4","pred":"source","obj":"name_no"},{"subj":"T5","pred":"source","obj":"name_no"},{"subj":"T6","pred":"source","obj":"name_no"},{"subj":"T7","pred":"source","obj":"name_no"},{"subj":"T8","pred":"source","obj":"name_no"},{"subj":"T9","pred":"source","obj":"name_no"},{"subj":"T10","pred":"source","obj":"name_no"},{"subj":"T13","pred":"source","obj":"name_no"},{"subj":"T11","pred":"source","obj":"name_no"},{"subj":"T12","pred":"source","obj":"name_no"},{"subj":"T14","pred":"source","obj":"name_no"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"sonoma2","color":"#9793ec","default":true},{"id":"PubmedHPO","color":"#a8ec93"},{"id":"kaiyin_test","color":"#ec93c2"},{"id":"name_no","color":"#93dcec"}]}]}}