E2F1 Mediates Death of B-amyloid-treated Cortical Neurons in a Manner Independent of p53 and Dependent on Bax and Caspase 3
| Autor: | Ruth S. Slack, George S. Robertson, David S. Park, Michael J. O'Hare, Andrew Giovanni, Nicholas J. Dyson, Erick J. Morris, Elizabeth Keramaris, Sheng T. Hou |
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| Rok vydání: | 2000 |
| Předmět: |
endocrine system
Apoptosis Cell Cycle Proteins Caspase 3 Biochemistry Mice Coumarins Proto-Oncogene Proteins Animals E2F1 Molecular Biology Transcription factor Cells Cultured Caspase bcl-2-Associated X Protein Cerebral Cortex Mice Knockout Neurons Amyloid beta-Peptides biology Kinase NLRP1 Retinoblastoma protein Cell Biology E2F Transcription Factors Cell biology DNA-Binding Proteins Enzyme Activation Mice Inbred C57BL Proto-Oncogene Proteins c-bcl-2 Caspases Cancer research biology.protein Tumor Suppressor Protein p53 biological phenomena cell phenomena and immunity Carrier Proteins Oligopeptides Transcription Factor DP1 E2F1 Transcription Factor Retinoblastoma-Binding Protein 1 Transcription Factors |
| Zdroj: | Journal of Biological Chemistry. 275:11553-11560 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.275.16.11553 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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