NATS 4210 Lecture Notes - Lecture 12: Ubiquitin Ligase, Procollagen-Proline Dioxygenase, Ubiquitin
14 Dec 2016
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Animals detect and respond to low oxygen at 2 different scales: whole body or systemic. Monitoring of blood po2 and responding by increasing or decreasing ventilation blood flow etc: intracellular. Elicited when the circulatory and breathing systems fail to meet the needs of the tissues. Hif-1 is a transcription factor that binds hypoxia-response elements of dna to activate gene transcription. Hif-1 translocates into the nucleus and dimerizes with hif1- . The hif-1 and hif1- subunits bind to a hypoxia-response element (hre) in target tissues. Hif-1 is regulated by prolyl hydroxylase domain (phd) enzymes. Hydroxylation is required for von hippel-lindau (vhl) tumour suppressor protein to bind to hif1- . Vhl then recruits e3 ubiquitin ligase which targets hif-1 for ubiquitination and proteasomal degradation. In response to hypoxia, proline hydroxylation is inhibited, vhl cannot bind hif- 1 and recruit e3 ubiquitin ligase and hence, no degradation of hif-1 .
