期刊
JOURNAL OF CELL BIOLOGY
卷 179, 期 5, 页码 825-832出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.200708086
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资金
- NINDS NIH HHS [NS049745, F31 NS049745, R01 NS042197, NS42197] Funding Source: Medline
Although apoptosis has been extensively studied in developing neurons, the dynamic changes in this pathway after neuronal maturation remain largely unexplored. We show that as neurons mature, cytochrome c-mediated apoptosis progresses from inhibitor of apoptosis protein - dependent to -independent regulation because of a complete loss of Apaf- 1 expression. However, after DNA damage, mature neurons resynthesize Apaf- 1 through the cell cycle - related E2F1 pathway and restore their apoptotic potential. Surprisingly, we find that E2F1 is sufficient to induce Apaf- 1 expression in developing but not mature neurons. Rather, Apaf-1 up-regulation in mature neurons requires both chromatin derepression and E2F1 transcriptional activity. This differential capacity of E2F1 to induce Apaf- 1 transcription is because of the association of the Apaf- 1 promoter with active chromatin in developing neurons and repressed chromatin in mature neurons. These data specifically illustrate how the apoptotic pathway in mature neurons becomes increasingly restricted by a novel mechanism involving the regulation of chromatin structure.
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