Hoffman B, Liebermann D A
Department of Biochemistry, Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, Philadelphia, PA 19140, USA.
Oncogene. 2008 Oct 27;27(50):6462-72. doi: 10.1038/onc.2008.312.
c-MYC has a pivotal function in growth control, differentiation and apoptosis, and its abnormal expression is associated with many tumors. Overexpression of c-MYC sensitizes cells to apoptosis by a variety of stimuli. The decision of a cell to undergo apoptosis and how this apoptotic response is regulated by c-MYC depends on the specific cell type and the physiological status of the cell. Multiple cooperating molecular pathways of cell survival and apoptosis determine whether a cell lives or dies, and understanding how c-MYC interfaces with these pathways to influence the survival of cells is important to understand normal and abnormal development, tumor initiation and progression, and response of tumors to different treatment regimens. This article will provide an overview of the function of the tumor suppressor gene product p53 in the c-MYC-mediated apoptotic response and how c-MYC amplifies the intrinsic mitochondrial pathway and triggers and/or amplifies the death receptor pathways. Finally, a model for how deregulated c-MYC prematurely triggers the normal apoptotic response associated with terminal myeloid differentiation while also blocking the differentiation program is presented.
c-MYC在生长控制、分化和细胞凋亡中起关键作用，其异常表达与多种肿瘤相关。c-MYC的过表达使细胞对多种刺激诱导的细胞凋亡敏感。细胞是否发生凋亡以及c-MYC如何调节这种凋亡反应取决于特定的细胞类型和细胞的生理状态。细胞存活和凋亡的多种协同分子途径决定了细胞的生死，了解c-MYC如何与这些途径相互作用以影响细胞存活对于理解正常和异常发育、肿瘤的发生和进展以及肿瘤对不同治疗方案的反应至关重要。本文将概述肿瘤抑制基因产物p53在c-MYC介导的凋亡反应中的作用，以及c-MYC如何放大内源性线粒体途径并触发和/或放大死亡受体途径。最后，提出了一个模型，说明失调的c-MYC如何过早触发与终末髓系分化相关的正常凋亡反应，同时也阻断分化程序。
