Stop and go -: Anti-proliferative and mitogenic functions of the transcription factor C/EBPβ
Stop and go -: Anti-proliferative and mitogenic functions of the transcription factor C/EBPβ
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DOI：
10.4161/cc.5.9.2733
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发表时间：
2006-05-01
期刊：
影响因子：
4.3
通讯作者：
Johnson, Peter F.
中科院分区：
文献类型：
--
作者：
Sebastian, Thomas;Johnson, Peter F.
癌基因诱导的衰老（OIS）是一种不可逆的细胞周期阻滞形式，可由癌基因如Ras（V12）的过度表达引发，需要激活Arf-p53和RB肿瘤抑制通路。越来越多的证据表明衰老在体内是一种真正的肿瘤抑制机制。我们最近发现bZIP转录因子C/EBP β是Ras信号的下游靶点，是Ras（V12）介导的小鼠胚胎成纤维细胞（mef）衰老的重要组成部分。C/EBP β通过RB:E2F抑制因子复合物的机制诱导细胞周期阻滞，并负调控多个E2F靶基因。尽管C/EBP β在mef中具有肿瘤抑制样活性，但其他观察结果指出，C/EBP β在某些癌症中具有关键的促癌功能。在这里，我们回顾了C/EBP β对细胞周期的正调控和负调控的证据，并讨论了该转录因子参与细胞衰老和致癌转化的可能机制。
Oncogene-induced senescence (OIS) is an irreversible form of cell cycle arrest that can be elicited by overexpression of oncogenes such as Ras(V12) and requires activation of the Arf-p53 and RB tumor suppressor pathways. Increasing evidence implicates senescence as a bona fide tumor suppression mechanism in vivo. We recently discovered that the bZIP transcription factor C/EBP beta, a downstream target of Ras signaling, is an essential component of Ras(V12)-mediated senescence in mouse embryo fibroblasts (MEFs). C/EBP beta induces cell cycle arrest through a mechanism requiring RB:E2F repressor complexes and negatively regulates several E2F target genes. Although C/EBP beta has tumor suppressor-like activity in MEFs, other observations point to critical pro-oncogenic functions for C/EBP beta in certain cancers. Here we review the evidence for positive and negative cell cycle regulation by C/EBP beta and discuss possible mechanisms by which this transcription factor could participate in both cellular senescence and oncogenic transformation.