CIP2A regulates cancer metabolism and CREB phosphorylation in non-small cell lung cancer.
CIP2A regulates cancer metabolism and CREB phosphorylation in non-small cell lung cancer.
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DOI：
10.1039/c4mb00513a
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发表时间：
2015-01
影响因子：
--
通讯作者：
Zhang JY
中科院分区：
文献类型：
--
作者：
Peng B;Lei N;Chai Y;Chan EK;Zhang JY
蛋白磷酸酶2A（protein phosphatase 2A，CIP 2A）是近年发现的一种内源性蛋白磷酸酶2A（protein phosphatase 2A，PP 2A）活性抑制剂，能延长致癌蛋白c-myc的半衰期，促进肿瘤生长。CIP 2A在癌症进展中的功能仍然知之甚少。为了揭示CIP 2A介导的细胞增殖的潜在机制，我们采用基于双向电泳（2DE）的蛋白质组学方法检测了肺癌细胞H1299与CIP 2A。我们发现了47个差异表达的蛋白质，其中19个蛋白质上调，28个蛋白质下调。这些被分类为代谢（25%），转录和翻译控制（23%），信号通路和蛋白质降解（20%）的功能组。一方面，我们通过测量代谢变化来验证我们的蛋白质组学工作。CIP 2A基因的敲低降低了乳酸脱氢酶A的表达，降低了酶活性，同时乳酸产量降低，NADH/NAD+比值增加，活性氧产生增加。另一方面，通过生物信息学分析，我们发现CIP 2A可能对CREB的活性有调节作用。我们的后续实验表明，CIP 2A正调节CREB的磷酸化响应于血清处理。因此，我们的蛋白质组学研究表明，CIP 2A通过代谢途径和细胞内信号级联介导癌症的进展。
Cancerous inhibitor of protein phosphatase 2A (CIP2A) is a recently characterized endogenous inhibitor of the phosphatase activity of protein phosphatase 2A (PP2A), which extends the half-life of oncogenic protein c-myc and promotes in vivo tumor growth. The function of CIP2A in cancer progression is still poorly understood. To uncover the underlying mechanism of CIP2A-mediated cell proliferation, we implemented two-dimensional electrophoresis (2DE)-based proteomic approach to examine lung cancer cell H1299 with and without CIP2A. We found 47 proteins differentially expressed where 19 proteins were upregulated and 28 proteins were downregulated. These were categorized into functional groups as metabolism (25%), transcriptional and translational control (23%), and signaling pathway and protein degradation (20%). On one hand, we validate our proteomic work by measuring the metabolic change. The knockdown of CIP2A decreased the expression of LDH-A as well as the enzymatic activity, accompanying with decreased lactate production, increased NADH/NAD+ ratio and ROS production. On the other hand, we found CIP2A may regulate CREB activity through bioinformatics analysis. Our following experiments showed that, CIP2A positively regulated the phosphorylation of CREB in response to the serum treatment. Therefore, our proteomic study suggested CIP2A mediate cancer progression through metabolic pathway and intracellular signaling cascade.
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影响因子：
5.6
作者：
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通讯作者：
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影响因子：
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作者：
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作者：
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3.3
作者：
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DOI：
10.1073/pnas.94.10.4884
发表时间：
1997-05-13
影响因子：
11.1
作者：
Ryazanov, AG;Ward, MD;Hait, WN
通讯作者：
Hait, WN