FIG. 8.

Schematic representation of the mechanisms involved in HIF-1α degradation following HDACI treatment. A. In the absence of HDACIs, newly synthesized HIF-1α molecules interact with its chaperones HSP70 and HSP90 to complete its maturation. Under normoxic conditions (+O₂), the mature protein is hydroxylated, ubiquitinated, and degraded by the 26S proteasome, while under hypoxia conditions (−O₂), the protein survives, interacts with ARNT, and binds hypoxia response element (HRE) sequences to initiate transcription. B. During HDACI treatment, HDAC-6 inhibition results in hyperacetylation of HSP90, accumulation of immature HIF-1α protein/HSP70 complex, and degradation of HIF-1α by the 20S proteasome.