CARF Is a Vital Dual Regulator of Cellular Senescence and Apoptosis
CARF Is a Vital Dual Regulator of Cellular Senescence and Apoptosis
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DOI：
10.1074/jbc.m805778200
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发表时间：
2009-01-16
影响因子：
4.8
通讯作者：
Wadhwa, Renu
中科院分区：
文献类型：
--
作者：
Hasan, Md. Kamrul;Cheung, Caroline;Wadhwa, Renu
肿瘤抑制蛋白 p53 是监测压力、DNA 损伤修复、细胞周期、衰老和癌症途径的核心。高度复杂的 p53 网络涉及其上游传感器和调节器、下游效应器和调节反馈环路，已被确定。 CARF（ARF 的合作者）被证明可以增强依赖于 ARF 和不依赖于 ARF 的野生型 p53 功能。在这里，我们报告（i）CARF过度表达导致人类成纤维细胞过早衰老，（ii）它对于复制和应激诱导的衰老至关重要，以及（iii）CARF功能的缺乏导致非整倍体和细胞凋亡。我们提供的证据表明，CARF 在调节 p53 介导的衰老和细胞凋亡（两种主要的肿瘤抑制机制）中发挥双重作用。
The tumor suppressor protein, p53, is central to the pathways that monitor the stress, DNA damage repair, cell cycle, aging, and cancer. Highly complex p53 networks involving its upstream sensors and regulators, downstream effectors and regulatory feedback loops have been identified. CARF (Collaborator of ARF) was shown to enhance ARF-dependent and -independent wild-type p53 function. Here we report that (i) CARF overexpression causes premature senescence of human fibroblasts, (ii) it is vital for replicative and stress-induced senescence, and (iii) the lack of CARF function causes aneuploidy and apoptosis. We provide evidence that CARF plays a dual role in regulating p53-mediated senescence and apoptosis, the two major tumor suppressor mechanisms.