Systematic and comprehensive insights into HIF-1 stabilization under normoxic conditions: implications for cellular adaptation and therapeutic strategies in cancer

Hypoxia-inducible factors (HIFs) are essential transcription factors that orchestrate cellular responses to oxygen deprivation. HIF-1α, as an unstable subunit of HIF-1, is usually hydroxylated by prolyl hydroxylase domain enzymes under normoxic conditions, leading to ubiquitination and proteasomal degradation, thereby keeping low levels. Instead of hypoxia, sometimes even in normoxia, HIF-1α translocates into the nucleus, dimerizes with HIF-1β to generate HIF-1, and then activates genes involved in adaptive responses such as angiogenesis, metabolic reprogramming, and cellular survival, which presents new challenges and insights into its role in cellular processes. Thus, the review delves into the mechanisms by…

• SM
  Southwest Medical University

  Awards: 05/00170050, 2024ZKZ008
• SP
  Sichuan Province Science and Technology Support Program

  Award: 2022YFS0623