Soengas M S, Alarcón R M, Yoshida H, Giaccia A J, Hakem R, Mak T W, Lowe S W
Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
Science. 1999 Apr 2;284(5411):156-9. doi: 10.1126/science.284.5411.156.
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.
p53响应促有丝分裂致癌基因促进细胞凋亡的能力，对于其肿瘤抑制功能似乎至关重要。在Myc诱导的细胞凋亡中，半胱天冬酶-9及其辅助因子Apaf-1被发现是p53必不可少的下游组分。与p53缺失的细胞一样，缺乏Apaf-1和半胱天冬酶-9且表达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。在促进表达Myc的细胞发生致癌转化方面，Apaf-1或半胱天冬酶-9的失活替代了p53缺失的作用。这些结果表明Apaf-1和半胱天冬酶-9在控制肿瘤发展中发挥作用。
