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

  • Published online on: July 1, 2006     https://doi.org/10.3892/ijo.29.1.255
  • Pages: 255-260
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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.

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July 2006
Volume 29 Issue 1

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Kim H, Yeo E, Chun Y and Park J: A domain responsible for HIF-1α degradation by YC-1, a novel anticancer agent. Int J Oncol 29: 255-260, 2006
APA
Kim, H., Yeo, E., Chun, Y., & Park, J. (2006). A domain responsible for HIF-1α degradation by YC-1, a novel anticancer agent. International Journal of Oncology, 29, 255-260. https://doi.org/10.3892/ijo.29.1.255
MLA
Kim, H., Yeo, E., Chun, Y., Park, J."A domain responsible for HIF-1α degradation by YC-1, a novel anticancer agent". International Journal of Oncology 29.1 (2006): 255-260.
Chicago
Kim, H., Yeo, E., Chun, Y., Park, J."A domain responsible for HIF-1α degradation by YC-1, a novel anticancer agent". International Journal of Oncology 29, no. 1 (2006): 255-260. https://doi.org/10.3892/ijo.29.1.255