CREB is a key negative regulator of carbonic anhydrase IX (CA9) in gastric cancer
CREB is a key negative regulator of carbonic anhydrase IX (CA9) in gastric cancer
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CREB 是胃癌中碳酸酐酶 IX (CA9) 的关键负调节因子
DOI：
10.1016/j.cellsig.2015.03.019
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发表时间：
2015
影响因子：
4.8
通讯作者：
Li Feng
中科院分区：
文献类型：
--
作者：
Wang Guanqiao;Cheng Zhenguo;Liu Funan;Zhang Hongyan;Li Jiabin;Li Feng
碳酸酐酶IX(CA9)是碳酸酐酶家族中的一员，催化二氧化碳的可逆水合反应，在调节pH中起着关键作用。虽然大量研究表明，CA9在HIF1-α的作用下有较强的上调作用，但对其在癌细胞中的负调控机制却知之甚少。在此，我们发现CREB是CA9在胃癌中的关键负性调节因子。CREB过表达可显著抑制CA9的表达。P38的激活剂茴香霉素(ANS)可促进CREB的磷酸化和核转位，抑制CA9的转录。此外，我们的结果首先证实CREB可以通过适配蛋白p300募集SIRT1(III类HDAC)，然后抑制CA9的表达。这些结果可能有助于理解CA9在胃癌中的负调控机制。
Carbonic anhydrase IX(CA9)is a member of the carbonic anhydrase family that catalyzes the reversible hydration of carbon dioxide, and plays a key role in the regulation of pH. Although a large number of studies have shown that CA9 is strongly up-regulated by HIF1-α, little is known about the negative regulation mechanism of CA9 in cancer cells. Here we find that CREB is a key negative regulator of CA9 in gastric cancer. Over-expression of CREB can significantly repress the expression of CA9. Treating with anisomycin (ANS), an activator of p38, the phosphorylation and nuclear translocation of CREB are both promoted, while the transcription of CA9 is repressed. Besides, our results firstly identify that CREB can recruit SIRT1 (class III HDACS) by adaptor protein p300, then repress the expression of CA9. These findings may contribute to understand the negative regulation mechanisms of CA9 in gastric cancer.