Induction of ARF tumor suppressor gene expression and cell cycle arrest by transcription factor DMP1
Induction of ARF tumor suppressor gene expression and cell cycle arrest by transcription factor DMP1
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DOI：
10.1073/pnas.96.7.3993
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发表时间：
1999-03-30
影响因子：
11.1
通讯作者：
Sherr, CJ
中科院分区：
文献类型：
--
作者：
Inoue, K;Roussel, MF;Sherr, CJ
DMP 1转录因子（一种细胞周期蛋白D结合Myb样蛋白）的表达诱导小鼠胚胎成纤维细胞株生长停滞，但在缺乏ARF肿瘤抑制基因的原代二倍体成纤维细胞中缺乏抗增殖活性。DMP 1与ARF启动子中的单一典型识别位点结合以激活基因表达，反过来，p19（ARF）合成导致p53依赖性细胞周期停滞。与Myc、腺病毒E1 A和E2 F-1等基因不同，当它们过度表达时，会激活ARF-p53通路并引发细胞凋亡，而DMP 1与ARF本身一样，不会诱导程序性细胞死亡。因此，除了最近认识到的保护细胞免受潜在致癌信号影响的作用外，ARF还可以在抗增殖刺激物的反应中诱导，而这些刺激物不会强制性地导致细胞凋亡。
Expression of the DMP1 transcription factor, a cyclin D-binding Myb-like protein, induces growth arrest in mouse embryo fibroblast strains but is devoid of antiproliferative activity in primary diploid fibroblasts that lack the ARF tumor suppressor gene. DMP1 binds to a single canonical recognition site in the ARF promoter to activate gene expression, and in turn, p19(ARF) synthesis causes p53-dependent cell cycle arrest. Unlike genes such as Myc, adenovirus E1A, and E2F-1, which, when overexpressed, activate the ARF-p53 pathway and trigger apoptosis, DMP1, like ARF itself, does not induce programmed cell death. Therefore, apart from its recently recognized role in protecting cells from potentially oncogenic signals, ARF can be induced in response to antiproliferative stimuli that do not obligatorily lead to apoptosis.