Cancer Stem Cells: From an Insight into the Basics to Recent Advances and Therapeutic Targeting

Figure 3

Structural and functional organization of hypoxic inducible factors (HIFs). HIF is a heterodimeric complex composed of an oxygen-dependent α-subunit (HIF-α) and an oxygen-insensitive β-subunit (HIF-β). The HIF-α has three subunits (HIF-1α, HIF-2α, and HIF-3α). The regulation of HIF-1α and HIF-2α is done by oxygen tension and is ubiquitously expressed in the normal tissue, whereas the HIF-1β is the subunit of HIF-β. The carboxy-terminal domain (CTD) of HIF-1α and HIF-2α based on their regulation is divided (indicated by black arrows) into two domains: ODD (regulates stability) and TAD (regulates transcriptional activity via two transactivation domains (TADs))—(i) N-TAD and (ii) C-TAD. Some nuclear localization signals (NLS) are present in both the C and N-termini of the α-subunits such as N-NLS and C-NLS that give it the direction towards the nucleus.