| First Author | Giovanni A | Year | 2000 |
| Journal | J Biol Chem | Volume | 275 |
| Issue | 16 | Pages | 11553-60 |
| PubMed ID | 10766769 | Mgi Jnum | J:61737 |
| Mgi Id | MGI:1355481 | Doi | 10.1074/jbc.275.16.11553 |
| Citation | Giovanni A, et al. (2000) E2F1 mediates death of B-amyloid-treated cortical neurons in a manner independent of p53 and dependent on Bax and caspase 3. J Biol Chem 275(16):11553-60 |
| abstractText | Although B-amyloid (AB) is suggested to play an important role in Alzheimer's disease, the mechanisms that control AB-evoked toxicity are unclear. We demonstrated previously that the cell cycle-related cyclin-dependent kinase 4/6/retinoblastoma protein pathway is required for AB-mediated death. However, the downstream target(s) of this pathway are unknown. We show here that neurons lacking E2F1, a transcription factor regulated by the retinoblastoma protein, are significantly protected from death evoked by AB. Moreover, p53 deficiency does not protect neurons from death, indicating that E2F1-mediated death occurs independently of p53. Neurons protected by E2F1 deficiency have reduced Bax-dependent caspase 3-like activity. However, protection afforded by E2F1, Bax, or caspase 3 deficiency is transient. In the case of E2F1, but not with Bax or caspase 3 deficiency, delayed death is accompanied by DEVD-AFC cleavage activity. Taken together, these results demonstrate the required role of E2F1, Bax, and caspase 3 in AB evoked death, but also suggest the participation of elements independent of these apoptosis regulators. |
