Molecular stop signs: regulation of cell-cycle arrest by C/EBP transcription factors
Molecular stop signs: regulation of cell-cycle arrest by C/EBP transcription factors
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DOI：
10.1242/jcs.02459
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发表时间：
2005-06-15
影响因子：
4
通讯作者：
Johnson, PF
中科院分区：
文献类型：
--
作者：
Johnson, PF
转录因子CCAAT/增强子结合蛋白（C/EBP）家族在控制细胞增殖和分化中发挥着重要作用。 C/EBP α 是细胞周期退出的特别有效的调节剂，在终末分化的脂肪细胞和骨髓细胞中被诱导，它还激活分化特异性基因。 C/EBP α 的生长抑制活性可抑制骨髓细胞和其他组织中的肿瘤发生。此外，最近的工作已确定 C/EBP α 是表皮角质形成细胞中 DNA 损伤引起的 p53 调节的生长停滞反应的一个组成部分。多项研究探索了 C/EBP α 在 G1-S 边界阻断细胞周期进程的机制，并提出了几种模型，但尚未出现普遍接受的机制。有争议的问题包括 C/EBP α 是否通过“脱 DNA”机制发挥作用来抑制细胞周期蛋白依赖性激酶，以及它是否以及如何与 RB-E2F 系统一起发挥作用来抑制 S 期基因的转录。其他 C/EBP 家族成员也与细胞增殖的正向和负向控制有关，并且其生长调节活性的机制正开始被阐明。
The CCAAT/enhancer-binding protein (C/EBP) family of transcription factors plays an important role in controlling cell proliferation and differentiation. C/EBP alpha is a particularly potent regulator of cell-cycle exit and is induced in terminally differentiating adipocytes and myeloid cells, where it also activates differentiation-specific genes. The growth-inhibiting activity of C/EBP alpha suppresses tumorigenesis in myeloid cells and possibly other tissues. In addition, recent work has identified C/EBP alpha as a component of the p53-regulated growth arrest response elicited by DNA damage in epidermal keratinocytes. Several studies have explored the mechanism by which C/EBP alpha blocks cell-cycle progression at the G1-S boundary, and several models have been proposed but no universally accepted mechanism has emerged. Controversial issues include whether C/EBP alpha acts through an 'off-DNA' mechanism to inhibit cyclin-dependent kinases, and whether and how it functions with the RB-E2F system to repress transcription of S-phase genes. Other C/EBP-family members have also been implicated in positive and negative control of cell proliferation, and the mechanisms underlying their growth-regulatory activities are beginning to be elucidated.