A domain responsible for HIF-1α degradation by YC-1, a novel anticancer agent

Kim,Hye-Lim; Yeo,Eun-Jin; Chun,Yang-Sook; Park,Jong-Wan

doi:10.3892/ijo.29.1.255

July 2006 Volume 29 Issue 1

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July 2006 Volume 29 Issue 1

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Article

A domain responsible for HIF-1α degradation by YC-1, a novel anticancer agent

Authors:
- Hye-Lim Kim
- Eun-Jin Yeo
- Yang-Sook Chun
- Jong-Wan Park
View Affiliations / Copyright

Affiliations: Department of Pharmacology, Seoul National University College of Medicine, Chongno-gu, Seoul 110-799, Korea
Pages: 255-260
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Published online on: July 1, 2006

https://doi.org/10.3892/ijo.29.1.255
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Abstract

HIF-1α is believed to promote tumor growth and metastasis, and many efforts have been made to develop new anticancer agents based on HIF-1α inhibition. YC-1 is a widely used HIF-1α inhibitor both in vitro and in vivo, and is being developed as a novel class of anticancer drug. However, little is known about the mechanism by which YC-1 degrades HIF-1α. As the first step for understanding the mechanism of action of YC-1, we here identified the HIF-1α domain responsible for YC-1-induced protein degradation. YC-1 blocked the HIF-1α induction by hypoxia, iron chelation, and proteasomal inhibition and also degraded ectopically expressed HIF-1α. In deletion analyses, C-terminal HIF-1α was found to be sensitively degraded by YC-1. Using a GFP-fusion method, the YC-1-induced degradation domain was identified as the aa. 720-780 region of HIF-1α. We next tested the possible involvement of HDAC7 or OS-9 in YC-1-induced HIF-1α degradation. However, their binding to HIF-1α was not affected by YC-1, suggesting that they are not involved in the YC-1 action. It is also suggested that YC-1 targets a novel pathway regulating HIF-1α stability.

Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

A domain responsible for HIF-1α degradation by YC-1, a novel anticancer agent

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Abstract

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