p53-induced apoptosis as a safeguard against cancer
p53-induced apoptosis as a safeguard against cancer
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DOI：
10.1006/bbrc.1999.1446
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发表时间：
1999-11-11
影响因子：
3.1
通讯作者：
Selivanova, G
中科院分区：
文献类型：
--
作者：
Asker, C;Wiman, KG;Selivanova, G
p53主要通过其通过凋亡诱导细胞死亡的能力而作为有效的肿瘤抑制因子。不同的细胞应激条件，例如，DNA损伤、缺氧和癌基因激活触发p53依赖性细胞凋亡。ARF是一种14 kDa蛋白，由人INK 4 a基因座内的另一个阅读框编码，也编码p16蛋白。ARF通过阻止p53降解诱导p53对癌基因激活的反应。这确保了通过p53依赖性凋亡消除新出现的肿瘤细胞。p53通过多种机制促进细胞凋亡，包括特定靶基因的反式激活、一组不同基因的下调和转录非依赖性机制。这可能解释了在肿瘤发展过程中ARF/p53而不是下游效应物的频繁失活。(C)北京：科学出版社.
p53 acts as a potent tumor suppressor largely through its ability to induce cell death by apoptosis. Diverse cellular stress conditions, e.g., DNA damage, hypoxia, and oncogene activation, trigger p53-dependent apoptosis. ARF is a 14-kDa protein encoded by an alternative reading frame within the human INK4a locus that also encodes the p16 protein. ARF induces p53 in response to oncogene activation by preventing its degradation. This ensures the elimination of emerging tumor cells by p53-dependent apoptosis. p53 promotes apoptosis through multiple mechanisms, including transactivation of specific target genes, down-regulation of a distinct set of genes, and transcription-independent mechanisms. This may explain the frequent inactivation of ARF/p53 rather than downstream effecters during tumor development. (C) 1999 Academic Press.