A functional link between the tumour suppressors ARF and p33ING1
A functional link between the tumour suppressors ARF and p33ING1
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DOI：
10.1038/sj.onc.1209526
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发表时间：
2006-08-24
期刊：
影响因子：
8
通讯作者：
Palmero, I.
中科院分区：
文献类型：
--
作者：
Gonzalez, L.;Freije, J. M. P.;Palmero, I.
ARF肿瘤抑制蛋白在响应致癌应激的p53活化中起关键作用。ARF可以通过Mdm 2的核仁隔离激活p53。然而，一些证据表明，这不是ARF的唯一作用方式，必须存在替代机制。p33ING1是一种公认的肿瘤抑制因子，其以p53依赖的方式诱导细胞周期停滞和凋亡。在这里，我们描述了ARF和p33ING1可以在体内相互作用。我们还表明，ING1的亚细胞定位可以通过ARF蛋白水平进行调节，导致从核到核仁定位的位移。最后，在ARF缺陷的原代小鼠成纤维细胞中，p33ING1引起细胞周期停滞和诱导p21CIP1或Mdm 2的能力受损。基于这些观察，我们提出与p33ING1的相互作用代表了ARF的肿瘤抑制功能的新机制。
The ARF tumour suppressor protein plays a critical role in the activation of p53 in response to oncogenic stress. ARF can activate p53 through nucleolar sequestration of Mdm2. However, several lines of evidence indicate that this is not the only way of action of ARF, and alternative mechanisms must exist. p33ING1 is a putative tumour suppresor, which induces cell-cycle arrest and apoptosis in a p53-dependent manner. Here, we describe that ARF and p33ING1 can interact in vivo. We also show that the subcellular localization of ING1 can be modulated by ARF protein levels, causing a displacement from nuclear to nucleolar localization. Finally, the ability of p33ING1 to cause cell-cycle arrest and induction of p21CIP1, or Mdm2, is impaired in ARF-deficient primary mouse fibroblasts. Based on these observations, we propose that the interaction with p33ING1 represents a novel mechanism for the tumour suppression function of ARF.