Histone deacetylase inhibitors (HDACIs) are currently in clinical trials partly due to their potent anti-angiogenic effects. However, the detailed mechanism of their action is unclear. Here, we observed that several HDACIs (TSA, SB, Apicidin, and VPA) dramatically decreased HIF-1α protein level and transcriptional activity of HIF-1 in human and mouse tumor cell lines. Furthermore, class I HDACs, HDAC1 and 3 enhanced HIF-1α stability and HIF-1 transactivation function in hypoxic conditions. In addition, immunoprecipitation and in vitro binding assays revealed that HDAC1 and 3 directly bind to the oxygen-dependent degradation domain of HIF-1α. Collectively, these results suggest that HDAC1 and 3 are considered as a positive regulator of HIF-1α stability via direct interaction and may play an important role in HIF-1-induced tumor angiogenesis.
CITATION STYLE
Kim, S. H., Jeong, J. W., Park, J. A., Lee, J. W., Seo, J. H., Jung, B. K., … Kim, K. W. (2007). Regulation of the HIF-1α stability by histone deacetylases. Oncology Reports, 17(3), 647–651. https://doi.org/10.3892/or.17.3.647
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