http://purl.uniprot.org/citations/17471234 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
http://purl.uniprot.org/citations/17471234 | http://www.w3.org/2000/01/rdf-schema#comment | "E2F-1 controls multiple cellular activities through transcriptional regulation of its target genes. As a mediator of cell death, E2F-1 can eliminate latent neoplastic cells through apoptosis. However, the mechanism by which E2F-1 mediates cancer cell killing is largely unknown. In this paper, we report that phosphatase of activated cells 1 (PAC1) phosphatase is a direct transcription target of E2F-1 in signaling apoptosis. We show that ectopic E2F-1 increases expression of PAC1 at both transcriptional and translational levels in breast cancer cells. E2F-1 physically interacts with the promoter of PAC1, binds to its consensus sequence in the promoter and transactivates the PAC1 promoter. E2F-1 suppresses extracellular signal-regulated kinase (ERK) phosphorylation through PAC1 and causes cancer cell death by apoptosis following treatment with a chemotherapeutic agent N-4-hydroxyphenylretinamide (4-HPR). Furthermore, ectopic PAC1 inhibits ERK phosphorylation and mediates cell killing. Moreover, endogenous E2F-1 upregulates PAC1 and suppresses ERK activity, leading to cell death in response to 4-HPR. These results reveal a crucial role of PAC1 in E2F-1-directed apoptosis. Our study demonstrates that E2F-1 mediates apoptosis through transcriptional regulation of PAC1 and subsequent suppression of the ERK signaling. Our findings establish a functional link between E2F-1 and mitogen-activated protein kinases. The E2F-1-PAC1 cascade in cancer cell killing may provide a molecular basis for cancer therapeutic intervention."xsd:string |
http://purl.uniprot.org/citations/17471234 | http://purl.org/dc/terms/identifier | "doi:10.1038/sj.onc.1210484"xsd:string |
http://purl.uniprot.org/citations/17471234 | http://purl.uniprot.org/core/author | "Wu J."xsd:string |
http://purl.uniprot.org/citations/17471234 | http://purl.uniprot.org/core/author | "Yin Y."xsd:string |
http://purl.uniprot.org/citations/17471234 | http://purl.uniprot.org/core/author | "Jin Y.J."xsd:string |
http://purl.uniprot.org/citations/17471234 | http://purl.uniprot.org/core/author | "Huang W.L."xsd:string |
http://purl.uniprot.org/citations/17471234 | http://purl.uniprot.org/core/author | "Calaf G.M."xsd:string |
http://purl.uniprot.org/citations/17471234 | http://purl.uniprot.org/core/date | "2007"xsd:gYear |
http://purl.uniprot.org/citations/17471234 | http://purl.uniprot.org/core/name | "Oncogene"xsd:string |
http://purl.uniprot.org/citations/17471234 | http://purl.uniprot.org/core/pages | "6526-6535"xsd:string |
http://purl.uniprot.org/citations/17471234 | http://purl.uniprot.org/core/title | "PAC1 is a direct transcription target of E2F-1 in apoptotic signaling."xsd:string |
http://purl.uniprot.org/citations/17471234 | http://purl.uniprot.org/core/volume | "26"xsd:string |
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