HIF-1 (hypoxia inducible factor 1) performs a crucial role in mediating the response to hypoxia. However, other transcription factors are also capable of regulating hypoxia-induced target-gene transcription. In a previous report, we demonstrated that the transcription factor ATF-2 (activating transcription factor 2) regulates hypoxia-induced gene transcription, along with HIF-1α. In the present study, we show that the protein stability of ATF-2 is induced by hypoxia and the hypoxia-mimic CoCl2 (cobalt chloride), and that ATF-2 induction enhances HIF-1α protein stability via direct protein interaction. The knockdown of ATF-2 using small interfering RNA and translation-inhibition experiments demonstrated that ATF-2 plays a key role in the maintenance of the expression level and transcriptional activity of HIF-1α. Furthermore, we determined that ATF-2 interacts directly with HIF-1α both in vivo and in vitro and competes with the tumour suppressor protein p53 for HIF-1α binding. Collectively, these results show that protein stabilization of ATF-2 under hypoxic conditions is required for the induction of the protein stability and transactivation activity of HIF-1α for efficient hypoxia-associated gene expression.
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Research Article|
November 11 2009
Activating transcription factor 2 increases transactivation and protein stability of hypoxia-inducible factor 1α in hepatocytes
Jeong Hae Choi;
Jeong Hae Choi
*Department of Molecular Biology, College of Natural Sciences, Pusan National University, Busan 609-735, Republic of Korea
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Hyun Kook Cho;
Hyun Kook Cho
*Department of Molecular Biology, College of Natural Sciences, Pusan National University, Busan 609-735, Republic of Korea
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Yung Hyun Choi;
Yung Hyun Choi
†Department of Oriental Medicine, Dong-Eui University, Busan, 602-243, Republic of Korea
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JaeHun Cheong
JaeHun Cheong
1
*Department of Molecular Biology, College of Natural Sciences, Pusan National University, Busan 609-735, Republic of Korea
1To whom correspondence should be addressed (e-mail molecule85@pusan.ac.kr).
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Publisher: Portland Press Ltd
Received:
March 03 2009
Revision Received:
August 14 2009
Accepted:
August 27 2009
Accepted Manuscript online:
August 27 2009
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2009 Biochemical Society
2009
Biochem J (2009) 424 (2): 285–296.
Article history
Received:
March 03 2009
Revision Received:
August 14 2009
Accepted:
August 27 2009
Accepted Manuscript online:
August 27 2009
Citation
Jeong Hae Choi, Hyun Kook Cho, Yung Hyun Choi, JaeHun Cheong; Activating transcription factor 2 increases transactivation and protein stability of hypoxia-inducible factor 1α in hepatocytes. Biochem J 1 December 2009; 424 (2): 285–296. doi: https://doi.org/10.1042/BJ20090371
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