CREB is a key negative regulator of carbonic anhydrase IX (CA9) in gastric cancer

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 negativ...

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Veröffentlicht in:Cellular signalling 2015-07, Vol.27 (7), p.1369-1379
Hauptverfasser: Wang, Guanqiao, Cheng, Zhenguo, Liu, Funan, Zhang, Hongyan, Li, Jiabin, Li, Feng
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container_end_page 1379
container_issue 7
container_start_page 1369
container_title Cellular signalling
container_volume 27
creator Wang, Guanqiao
Cheng, Zhenguo
Liu, Funan
Zhang, Hongyan
Li, Jiabin
Li, Feng
description 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.
doi_str_mv 10.1016/j.cellsig.2015.03.019
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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. 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subjects Animals
Anisomycin - pharmacology
Antigens, Neoplasm - genetics
Antigens, Neoplasm - metabolism
Carbonic Anhydrase IX
Carbonic Anhydrases - genetics
Carbonic Anhydrases - metabolism
Cell Line, Tumor
CREB-Binding Protein - metabolism
Down-Regulation
Humans
Hypoxia-Inducible Factor 1, alpha Subunit - metabolism
Mice
Mice, Inbred BALB C
Mice, Nude
p300-CBP Transcription Factors - metabolism
p38 Mitogen-Activated Protein Kinases - chemistry
p38 Mitogen-Activated Protein Kinases - metabolism
Phosphorylation - drug effects
Promoter Regions, Genetic
Protein Synthesis Inhibitors - pharmacology
RNA, Messenger - metabolism
Sirtuin 1 - metabolism
Stomach Neoplasms - enzymology
Stomach Neoplasms - metabolism
Stomach Neoplasms - pathology
Transcription, Genetic - drug effects
Transplantation, Heterologous
title CREB is a key negative regulator of carbonic anhydrase IX (CA9) in gastric cancer
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