| http://purl.uniprot.org/citations/20808790 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/20808790 | http://www.w3.org/2000/01/rdf-schema#comment | "The pro-apoptotic function of p53 has been well defined in preventing genomic instability and cell transformation. However, the intriguing fact that p53 contributes to a pro-survival advantage of tumor cells under DNA damage conditions raises a critical question in radiation therapy for the 50% human cancers with intact p53 function. Herein, we reveal an anti-apoptotic role of mitochondrial p53 regulated by the cell cycle complex cyclin B1/Cdk1 in irradiated human colon cancer HCT116 cells with p53(+/+) status. Steady-state levels of p53 and cyclin B1/Cdk1 were identified in the mitochondria of many human and mouse cells, and their mitochondrial influx was significantly enhanced by radiation. The mitochondrial kinase activity of cyclin B1/Cdk1 was found to specifically phosphorylate p53 at Ser-315 residue, leading to enhanced mitochondrial ATP production and reduced mitochondrial apoptosis. The improved mitochondrial function can be blocked by transfection of mutant p53 Ser-315-Ala, or by siRNA knockdown of cyclin B1 and Cdk1 genes. Enforced translocation of cyclin B1 and Cdk1 into mitochondria with a mitochondrial-targeting-peptide increased levels of Ser-315 phosphorylation on mitochondrial p53, improved ATP production and decreased apoptosis by sequestering p53 from binding to Bcl-2 and Bcl-xL. Furthermore, reconstitution of wild-type p53 in p53-deficient HCT116 p53(-/-) cells resulted in an increased mitochondrial ATP production and suppression of apoptosis. Such phenomena were absent in the p53-deficient HCT116 p53(-/-) cells reconstituted with the mutant p53. These results demonstrate a unique anti-apoptotic function of mitochondrial p53 regulated by cyclin B1/Cdk1-mediated Ser-315 phosphorylation in p53-wild-type tumor cells, which may provide insights for improving the efficacy of anti-cancer therapy, especially for tumors that retain p53."xsd:string |
| http://purl.uniprot.org/citations/20808790 | http://purl.org/dc/terms/identifier | "doi:10.1371/journal.pone.0012341"xsd:string |
| http://purl.uniprot.org/citations/20808790 | http://purl.uniprot.org/core/author | "Fan M."xsd:string |
| http://purl.uniprot.org/citations/20808790 | http://purl.uniprot.org/core/author | "Wen Y."xsd:string |
| http://purl.uniprot.org/citations/20808790 | http://purl.uniprot.org/core/author | "Reed J.C."xsd:string |
| http://purl.uniprot.org/citations/20808790 | http://purl.uniprot.org/core/author | "Li J.J."xsd:string |
| http://purl.uniprot.org/citations/20808790 | http://purl.uniprot.org/core/author | "Nantajit D."xsd:string |
| http://purl.uniprot.org/citations/20808790 | http://purl.uniprot.org/core/author | "Duru N."xsd:string |
| http://purl.uniprot.org/citations/20808790 | http://purl.uniprot.org/core/date | "2010"xsd:gYear |
| http://purl.uniprot.org/citations/20808790 | http://purl.uniprot.org/core/name | "PLoS One"xsd:string |
| http://purl.uniprot.org/citations/20808790 | http://purl.uniprot.org/core/pages | "e12341"xsd:string |
| http://purl.uniprot.org/citations/20808790 | http://purl.uniprot.org/core/title | "Cyclin B1/Cdk1 phosphorylation of mitochondrial p53 induces anti-apoptotic response."xsd:string |
| http://purl.uniprot.org/citations/20808790 | http://purl.uniprot.org/core/volume | "5"xsd:string |
| http://purl.uniprot.org/citations/20808790 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/20808790 |
| http://purl.uniprot.org/citations/20808790 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/20808790 |
| http://purl.uniprot.org/uniprot/#_A0A0M4B4Y9-mappedCitation-20808790 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/20808790 |
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| http://purl.uniprot.org/uniprot/#_A0A087X1Q1-mappedCitation-20808790 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/20808790 |
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