HIF1A and neoplasm: Indeed, another E3 ubiquitin ligase F-box/WD repeat-containing protein 7 (FBW7), one of the most frequently mutated genes in human cancer and well known tumor suppressor [41], has been shown to target HIF-1α for proteasomal degradation in hypoxic conditions [42] and is also downregulated in glioblastoma patients compared with normal brain.