Induction and activation of the p53 pathway: a role for the protein kinase CK2?
Induction and activation of the p53 pathway: a role for the protein kinase CK2?
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DOI：
10.1007/s11010-011-0966-3
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发表时间：
2011-10-01
影响因子：
4.3
通讯作者：
Cox, Miranda
中科院分区：
文献类型：
--
作者：
Meek, David W.;Cox, Miranda
蛋白激酶CK 2有许多已建立的体外底物，但只是在过去几年中，我们才开始确定哪些是其真实的生理靶点，它们的磷酸化如何有助于调节正常细胞生理学，以及这些蛋白质的磷酸化如何影响疾病如癌症的发展。CK2的一种良好表征的体外底物是肿瘤抑制蛋白p53。然而，这种相互作用的生理性质从未完全确定。在本文中，我们总结了最近的一项研究，从我们的实验室显示，磷酸化的p53在Ser392，唯一的网站修改CK2在体外，是由一种新的机制，其中磷酸化的化学计量是由周转率的p53蛋白。这样的模型是完全一致的磷酸化的组成型活性蛋白激酶，如CK2。与此相反，虽然有压倒性的证据表明，CK2磷酸化p53在体外，是唯一可检测的Ser392蛋白激酶在细胞提取物中，我们的数据提出了不确定性，这种相互作用是否真正反映了事件的基础Ser392磷酸化在体内。我们认为CK2在更广泛的背景下调节p53反应的可能作用，并提出了一些关键问题，这些问题应该通过实验来解决，以提供一个更有凝聚力的图片，这个重要的蛋白激酶和细胞中的一个关键抗癌监测系统之间的关系。
Protein kinase CK2 has many established in vitro substrates, but it is only within the past few years that we have begun to ascertain which of these are its real physiological targets, how their phosphorylation may contribute towards regulating normal cell physiology, and how phosphorylation of these proteins might influence the development of diseases such as cancer. One of the well-characterised in vitro substrates for CK2 is the tumour suppressor protein, p53. However, the physiological nature of this interaction has never been fully established. In the present article, we summarise a recent study from our laboratory showing that phosphorylation of p53 at Ser392, the sole site modified by CK2 in vitro, is regulated by a novel mechanism where the stoichiometry of phosphorylation is governed by the rate of turnover of the p53 protein. Such a model is entirely consistent with phosphorylation by a constitutively active protein kinase such as CK2. In contrast to this, while there is overwhelming evidence that CK2 phosphorylates p53 in vitro and is the only detectable Ser392 protein kinase in cell extracts, our data raise uncertainty as to whether this interaction truly reflects events underpinning Ser392 phosphorylation in vivo. We consider the possible role of CK2 in regulating the p53 response in a wider context and suggest key issues that should be addressed experimentally to provide a more cohesive picture of the relationship between this important protein kinase and a pivotal anti-cancer surveillance system in cells.