| First Author | Jordan-Sciutto KL | Year | 1998 |
| Journal | Biochem Cell Biol | Volume | 76 |
| Issue | 1 | Pages | 37-44 |
| PubMed ID | 9666304 | Mgi Jnum | J:48534 |
| Mgi Id | MGI:1270929 | Citation | Jordan-Sciutto KL, et al. (1998) A mutant E2F-1 transcription factor that affects the phenotype of NIH3T3 fibroblasts inefficiency associates with cyclin A-cdk2. Biochem Cell Biol 76(1):37-44 |
| abstractText | The amino-terminal domain of the E2F1 transcription factor is the site of association with cyclin A-cdk2, mapping to residues 87-94. A mutant of E2F1 lacking the first 87 amino acids (termed E2F1d87) has a number of potent effects on cellular phenotype when constitutively expressed in NIH3T3 fibroblasts. For example, in these fibroblasts the duration of S phase and the sensitivity to S phase chemotherapeutic agents are both increased. Since E2F1d87 only partially truncates the cyclin A-cdk2 binding domain, it was important to determine the level of cyclin A-cdk2 association with this mutant to correlate any reduction in association with the observed effects on the cell cycle. It was found that cyclin A-cdk2 binds E2F1d87 in an in vitro assay but that this binding is reduced approximately 8 fold compared with binding to full- length E2F1, whereas no detectable binding was seen to a mutant E2F1 that lacks the first 117 amino acids. Correspondingly, H1 kinase activity in E2F1d87 immunoprecipitates from E2F1d87-expressing cells was significantly reduced compared with that seen for full-length E2F1. From these data it appears that E2F1 with reduced cyclin A-cdk2 binding activity mediates the alteration in cell cycle parameters seen in these cells. |
