Apaf-1 and caspase-9 in p53-dependent apoptosis and tumor inhibition
Apaf-1 and caspase-9 in p53-dependent apoptosis and tumor inhibition
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DOI：
10.1126/science.284.5411.156
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发表时间：
1999-04-02
期刊：
影响因子：
56.9
通讯作者：
Lowe, SW
中科院分区：
文献类型：
--
作者：
Soengas, MS;Alarcón, RM;Lowe, SW
p53响应有丝分裂癌基因促进细胞凋亡的能力似乎对其抑癌功能至关重要，Caspase-9及其辅助因子Apaf-1被发现是p53在myc诱导的细胞凋亡中必不可少的下游成分。与p53缺失细胞一样，缺乏Apaf-1和caspase-9并表达c-Myc的小鼠胚胎成纤维细胞对模拟肿瘤发生条件的凋亡刺激具有抗性。Apaf-1或caspase-9失活取代p53缺失，促进myc表达细胞的癌性转化。这些结果暗示了Apaf-1和caspase-9在控制肿瘤发展中的作用。
The ability of p53 to promote apoptosis in response to mitogenic oncogenes appears to be critical for its tumor suppressor function, Caspase-9 and its cofactor Apaf-1 were found to be essential downstream components of p53 in Myc-induced apoptosis. Like p53 null cells, mouse embryo fibroblast cells deficient in Apaf-1 and caspase-9, and expressing c-Myc, were resistant to apoptotic stimuli that mimic conditions in developing tumors. Inactivation of Apaf-1 or caspase-9 substituted for p53 Loss in promoting the oncogenic transformation of Myc-expressing cells. These results imply a role for Apaf-1 and caspase-9 in controlling tumor development.