| First Author | Wang J | Year | 2007 |
| Journal | J Biol Chem | Volume | 282 |
| Issue | 25 | Pages | 18521-31 |
| PubMed ID | 17452331 | Mgi Jnum | J:123384 |
| Mgi Id | MGI:3718177 | Doi | 10.1074/jbc.M610538200 |
| Citation | Wang J, et al. (2007) A molecular link between E2F-1 and the MAPK cascade. J Biol Chem 282(25):18521-31 |
| abstractText | Transcription factor E2F-1 mediates apoptosis and suppresses tumorigenesis. The mechanisms by which E2F-1 functions in these processes are largely unclear. We report here that E2F-1 acts as a transcriptional regulator of MKP-2 (MAPK phosphatase-2), a dual specificity protein phosphatase (DUSP4) with stringent substrate specificity for MAPKs. We show that E2F-1 is required for the cellular apoptotic response to oxidative damage. MKP-2 is greatly increased following oxidative stress, and E2F-1 is necessary for that induction. We found that E2F-1 is physically associated with the MKP-2 promoter and can transactivate the promoter of the MKP-2 gene. Specifically, E2F-1 binds to a perfect palindromic motif in the MKP-2 promoter. Finally, we show that this E2F-1/MKP-2 pathway mediates apoptosis under oxidative stress and that MKP-2 suppresses tumor formation in nude mice. Our findings demonstrate that E2F-1 is a transcriptional activator of MKP-2 and that MKP-2 is an essential cell death mediator in the E2F-1 pathway. Characterization of MKP-2 as a cell death mediator may lead to the development of new strategies for cancer treatment. |
