HIF1A and neoplasm: Under normoxic conditions, the intracellular concentration of HIF-1α protein is low, not due to lower protein expression but because it is negatively regulated by proteolysis by the ubiquitin-proteasome system via the von Hippel–Lindau tumor suppressor; under hypoxic conditions, HIF-1α levels are stable and it translocates to the cell nucleus and associates with HIF-1β, and the HIF-1α/1β complex binds to the HRE of the DNA resulting in the transcription of various genes [46–48].