HIF-1 α (556-574) – Cancer Peptides

HIF-1 alpha (556-574) is derived from hypoxia-inducible factor 1-alpha (HIF-1 alpha), a subunit of the heterodimeric transcription factor HIF-1 and is responsible for maintaining oxygen homeostasis. HIF-1 alpha is expressed under hypoxic conditions and is oxygen sensitive. Hypoxia can occur in cancer, heart disease and pulmonary disorders. Structurally HIF-1 alpha contains a N-terminal transactivation domain (N-TAD) which stabilises HIF-1 alpha and a C-terminal transactivation domain (C-TAD) which under hypoxic conditions regulates the transcription of HIF-1 alpha. Moreover HIF-1 alpha features an oxygen dependent degradation domain containing two proline residues and a lysine532. The two proline residues are substrates of prolyl-4-hydroxylases (PHDs) which in the presence of sufficient oxygen, are hydroxylated. Similarly the lysine residue is acetylated by arrest-defective-1 and this is reduced in hypoxic conditions. These hydroxylated prolines and acetylated lysine target HIF-1 alpha for ubiquitination and degradation.