Hypoxia-inducible factor 1 alpha (HIF1α) is an essential part of the HIF-1 transcriptional complex that regulates angiogenesis, cellular metabolism and cancer development. In VHL-null kidney cancer cell lines, we previously reported that HIF1α proteins can be acetylated and inhibited by histone deacetylase inhibitors (HDACi) or specific siRNA against HDAC4. To investigate the mechanism and biological consequence of the inhibition, Studies have generated stable HDAC4 knockdown via shRNA in VHL-positive normal and cancer cell lines. It reported that HDAC4 regulates HIF1α protein acetylation and stability. Specifically, the HIF1α protein acetylation can be increased by HDAC4 shRNA and decreased by HDAC4 overexpression. Taken together, the novel biological relationship between HDAC4 and HIF1α presented here suggests a potential role for the deacetylase enzyme in regulating HIF-1, cancer cell response to hypoxia, and presents a more specific molecular target of inhibition.
Geng H, et al. HDAC4 protein regulates HIF1α protein lysine acetylation and cancer cell response to hypoxia[J]. Journal of Biological Chemistry, 2011, 286(44): 38095-38102.