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Cited by 235

The DOI matches its Crossref record; 11 of the 11 references it cites were found in a registry or an index.

AMP-activated Protein Kinase Activity Is Critical for Hypoxia-inducible Factor-1 Transcriptional Activity and Its Target Gene Expression under Hypoxic Conditions in DU145 Cells

Open access
Lee, Minyoung, Hwang, Jin-Taek, Lee, Hye-Jeong, Jung, Seung-Nam, Kang, Insug, Chi, Sung-Gil, Kim, Sung-Soo, Ha, Joohun·2003·Journal of Biological Chemistry

Abstract

AMP-activated protein kinase (AMPK) functions as an energy sensor to provide metabolic adaptations under the ATP-deprived conditions such as hypoxia. In the present study, we considered a role of AMPK in the adaptive response to hypoxia by examining whether AMPK is involved in the regulation of hypoxia-inducible factor-1 (HIF-1), a heterodimeric transcription factor that is critical for hypoxic induction of physiologically important genes. We demonstrate that hypoxia or CoCl2 rapidly activated AMPK in DU145 human prostate cancer cells, and its activation preceded the induction of HIF-1 alpha expression. Under these conditions, blockade of AMPK activity by a pharmacological or molecular approach significantly attenuated hypoxia-induced responses such as HIF-1 target gene expression, secretion of vascular endothelial growth factor, glucose uptake, and HIF-1-dependent reporter gene expression, indicating that AMPK is critical for the HIF-1 transcriptional activity and its target gene expression. Its functional requirement for HIF-1 activity was also demonstrated in several different cancer cell lines, but AMPK activation alone was not sufficient to stimulate the HIF-1 transcriptional activity. We further present data showing that AMPK transmits a positive signal for HIF-1 activity via a signaling pathway that is independent of phosphatidylinositol 3-kinase/AKT and several mitogen-activated protein kinases. Taken together, our results suggest that AMPK is a novel and critical component of HIF-1 regulation, implying its new roles in oxygen-regulated cellular phenomena.

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Metadata

Authors
Lee, M., Hwang, J.-T., Lee, H.-J., Jung, S.-N., Kang, I., Chi, S.-G., Kim, S.-S., & Ha, J.
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
2003-10
Volume
278
Issue
41
Pages
39653-39661
ISSN
0021-9258 (ISSN-L)
OpenAlex
W1980356545
Cited by
235
References
11
FWCI
4.05
Type
journal article
Language
en
Status
Retracted
Open access
hybrid

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CoChat. (2026). Citation check: AMP-activated Protein Kinase Activity Is Critical for Hypoxia-inducible Factor-1 Transcriptional Activity and Its Target Gene Expression under Hypoxic Conditions in DU145 Cells. https://app.cochat.ai/papers/10.1074/jbc.m306104200
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Lee, M., Hwang, J.-T., Lee, H.-J., Jung, S.-N., Kang, I., Chi, S.-G., Kim, S.-S., & Ha, J. (2003). AMP-activated Protein Kinase Activity Is Critical for Hypoxia-inducible Factor-1 Transcriptional Activity and Its Target Gene Expression under Hypoxic Conditions in DU145 Cells. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.m306104200

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