Hyoxia Indcible Facir
Concept of HIF Structure and stability regulation of HIF Biological functions of HIF Expression of HIF in ischemia and ischemic preconditioning
◼ Concept of HIF ◼ Structure and stability regulation of HIF ◼ Biological functions of HIF ◼ Expression of HIF in ischemia and ischemic preconditioning
HIF is a heterodimeric transcription factor composed of two subunits: ■(subunit(HlF-(1,HlF-〈2 and HIF- (3) ■®subunit(aryl hydrocarbon receptor nuclear translocator,ARNT),which is constitutively expressed in nucleus
◼ HIF is a heterodimeric transcription factor composed of two subunits: ◼ subunit (HIF- HIF – and HIF – ) ◼ subunit (aryl hydrocarbon receptor nuclear translocator, ARNT),which is constitutively expressed in nucleus
HIF-(isoforms NAD 826a. HlF-1aWT 6HLH PASa PASb ODD I CAD 82a. HlF-1aFL HIF.1a73 736a.a HlF-1aZ 557a.a HlF-1a516 16a HIF.1a785 826a.2 HIF-2a HIF-3a1 HIF-3a2 HlF-3a3 HIF-3a4 HIF-3a5 HIF-3a6
HIF- isoforms
PHD2 FIH.1 Hydroxylation HIF-1 a p p PAS ODDD TAD TAD 2 S-Nitrosation Phosphorylation ses bHLH and PAS domsins which are involved in N-TADies e ODDD.The DDD
growth factors receptor tyrosine kinase PI3K Ras MAPK Akt(PKB) Nucleus MEK Gene expression HIF-1 a synthesis HRE
Regulation of the stability/degradation and transactivation of HIF-lo Cytoplasm Nuclous o 300 og Bcar-15 B C000000000Xw T
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mn- 一罗歌 HRE cible factore 1E1》pathway unde latio the n RD. tein Gl-I
Normoxia polyubiquitination pVHL Degradation OH OH bHLH PAS P402 K532 P56 TAD TAD N803 P300/CBF ODD Hypoxia Transcriptional activation