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Hypoxia-Inducible Factor-1 Alpha (HIF-1α) is a crucial transcription factor that plays a significant role in cellular response to low oxygen levels (hypoxia). The human recombinant form of HIF-1α, specifically the 85 amino acid (a.a.) variant, is a truncated version of the full-length protein, designed for research and therapeutic purposes.
HIF-1α is a subunit of the heterodimeric transcription factor Hypoxia-Inducible Factor-1 (HIF-1), which also includes the beta subunit, known as the Aryl Hydrocarbon Receptor Nuclear Translocator (ARNT). The HIF-1 complex is essential for the regulation of genes involved in various physiological processes, including angiogenesis, metabolism, and cell survival under hypoxic conditions .
The 85 a.a. variant of HIF-1α retains the critical domains necessary for its function, including the basic helix-loop-helix (bHLH) domain and the Per-ARNT-Sim (PAS) domain. These domains are responsible for DNA binding and dimerization with ARNT, respectively .
HIF-1α is considered the master regulator of the cellular response to hypoxia. Under normal oxygen levels, HIF-1α is rapidly degraded by the proteasome. However, under hypoxic conditions, HIF-1α is stabilized and translocates to the nucleus, where it dimerizes with ARNT and binds to hypoxia-responsive elements (HREs) in the promoter regions of target genes .
The activation of HIF-1α leads to the transcription of various genes involved in:
The dysregulation of HIF-1α has been implicated in several pathophysiological conditions, including cancer, cardiovascular diseases, and chronic kidney disease. Overexpression of HIF-1α is commonly observed in tumors, where it promotes angiogenesis and metabolic adaptation, contributing to tumor growth and survival .
In addition to its role in cancer, HIF-1α is also involved in the response to ischemic conditions, such as myocardial infarction and stroke. Therapeutic strategies targeting HIF-1α are being explored to enhance tissue repair and regeneration in these conditions .
The human recombinant HIF-1α (85 a.a.) is widely used in research to study the molecular mechanisms of hypoxia response and to develop potential therapeutic interventions. It serves as a valuable tool for investigating the regulation of HIF-1α and its downstream targets, as well as for screening potential HIF-1α inhibitors .