| http://purl.uniprot.org/citations/16862142 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/16862142 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/16862142 | http://www.w3.org/2000/01/rdf-schema#comment | "p53 limits the proliferation of primary diploid fibroblasts by inducing a state of growth arrest named replicative senescence - a process which protects against oncogenic transformation and requires integrity of the p53 tumour suppressor pathway. However, little is known about the downstream target genes of p53 in this growth-limiting response. Here, we report that suppression of the p53 target gene encoding plasminogen activator inhibitor-1 (PAI-1) by RNA interference (RNAi) leads to escape from replicative senescence both in primary mouse embryo fibroblasts and primary human BJ fibroblasts. PAI-1 knockdown results in sustained activation of the PI(3)K-PKB-GSK3beta pathway and nuclear retention of cyclin D1, consistent with a role for PAI-1 in regulating growth factor signalling. In agreement with this, we find that the PI(3)K-PKB-GSK3beta-cyclin D1 pathway is also causally involved in cellular senescence. Conversely, ectopic expression of PAI-1 in proliferating p53-deficient murine or human fibroblasts induces a phenotype displaying all the hallmarks of replicative senescence. Our data indicate that PAI-1 is not merely a marker of senescence, but is both necessary and sufficient for the induction of replicative senescence downstream of p53."xsd:string |
| http://purl.uniprot.org/citations/16862142 | http://purl.org/dc/terms/identifier | "doi:10.1038/ncb1448"xsd:string |
| http://purl.uniprot.org/citations/16862142 | http://purl.org/dc/terms/identifier | "doi:10.1038/ncb1448"xsd:string |
| http://purl.uniprot.org/citations/16862142 | http://purl.uniprot.org/core/author | "Bernards R."xsd:string |
| http://purl.uniprot.org/citations/16862142 | http://purl.uniprot.org/core/author | "Bernards R."xsd:string |
| http://purl.uniprot.org/citations/16862142 | http://purl.uniprot.org/core/author | "Higgins P.J."xsd:string |
| http://purl.uniprot.org/citations/16862142 | http://purl.uniprot.org/core/author | "Higgins P.J."xsd:string |
| http://purl.uniprot.org/citations/16862142 | http://purl.uniprot.org/core/author | "Kortlever R.M."xsd:string |
| http://purl.uniprot.org/citations/16862142 | http://purl.uniprot.org/core/author | "Kortlever R.M."xsd:string |
| http://purl.uniprot.org/citations/16862142 | http://purl.uniprot.org/core/date | "2006"xsd:gYear |
| http://purl.uniprot.org/citations/16862142 | http://purl.uniprot.org/core/date | "2006"xsd:gYear |
| http://purl.uniprot.org/citations/16862142 | http://purl.uniprot.org/core/name | "Nat. Cell Biol."xsd:string |
| http://purl.uniprot.org/citations/16862142 | http://purl.uniprot.org/core/name | "Nat. Cell Biol."xsd:string |
| http://purl.uniprot.org/citations/16862142 | http://purl.uniprot.org/core/pages | "877-884"xsd:string |
| http://purl.uniprot.org/citations/16862142 | http://purl.uniprot.org/core/pages | "877-884"xsd:string |
| http://purl.uniprot.org/citations/16862142 | http://purl.uniprot.org/core/title | "Plasminogen activator inhibitor-1 is a critical downstream target of p53 in the induction of replicative senescence."xsd:string |
| http://purl.uniprot.org/citations/16862142 | http://purl.uniprot.org/core/title | "Plasminogen activator inhibitor-1 is a critical downstream target of p53 in the induction of replicative senescence."xsd:string |
| http://purl.uniprot.org/citations/16862142 | http://purl.uniprot.org/core/volume | "8"xsd:string |
| http://purl.uniprot.org/citations/16862142 | http://purl.uniprot.org/core/volume | "8"xsd:string |
| http://purl.uniprot.org/citations/16862142 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/16862142 |
| http://purl.uniprot.org/citations/16862142 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/16862142 |
| http://purl.uniprot.org/citations/16862142 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/16862142 |
| http://purl.uniprot.org/citations/16862142 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/16862142 |