Prendergast G C
The Wistar Institute, Philadelphia, Pennsylvania 19104, USA.
Oncogene. 1999 May 13;18(19):2967-87. doi: 10.1038/sj.onc.1202727.
Much recent research on c-Myc has focused on how it drives apoptosis. c-Myc is widely known as a crucial regulator of cell proliferation in normal and neoplastic cells, but until relatively recently its apoptotic properties, which appear to be intrinsic, were not fully appreciated. Its death-dealing aspects have gained wide attention in part because of their potential therapeutic utility in advanced malignancy, where c-Myc is frequently deregulated and where novel modalities are badly needed. Although its exact function remains obscure, c-Myc is a transcription factor and advances have been made in characterizing target genes which may mediate its apoptotic properties. Candidate regulators and effectors are also emerging. Among recent findings are connections to the CD95/Fas and TNF pathways and roles for the tumor suppressor p19ARF and the c-Myc-interacting adaptor protein Binl in mediating cell death. In this review I summarize the data establishing a role for c-Myc in apoptosis in diverse settings and present a modified dual signal model for c-Myc function. It is proposed that c-Myc induces apoptosis through separate 'death priming' and 'death triggering' mechanisms in which 'death priming' and mitogenic signals are coordinated. Investigation of the mechanisms that underlie the triggering steps may offer new therapeutic opportunities.
近期许多关于c-Myc的研究聚焦于其如何引发细胞凋亡。c-Myc作为正常细胞和肿瘤细胞中细胞增殖的关键调节因子广为人知，但直到最近，其似乎固有的凋亡特性才得到充分认识。它的促死亡作用受到广泛关注，部分原因在于其在晚期恶性肿瘤中的潜在治疗效用，在晚期恶性肿瘤中c-Myc常常失调，且急需新的治疗方式。尽管其确切功能仍不清楚，但c-Myc是一种转录因子，在表征可能介导其凋亡特性的靶基因方面已取得进展。候选调节因子和效应器也不断涌现。近期的发现包括与CD95/Fas和TNF途径的联系，以及肿瘤抑制因子p19ARF和与c-Myc相互作用的衔接蛋白Binl在介导细胞死亡中的作用。在这篇综述中，我总结了确立c-Myc在不同情况下凋亡作用的数据，并提出了一个修改后的c-Myc功能双信号模型。有人提出，c-Myc通过单独的“死亡启动”和“死亡触发”机制诱导细胞凋亡，其中“死亡启动”和促有丝分裂信号相互协调。对触发步骤背后机制的研究可能会带来新的治疗机会。
