Reactome: A Curated Pathway Database
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Regulation of gene expression by Hypoxia-inducible Factor

Stable Identifier
R-HSA-1234158
Type
Pathway
Species
Homo sapiens
Compartment
Locations in the PathwayBrowser
Summation

HIF-alpha (HIF1A, HIF2A (EPAS1), HIF3A) is translocated to the nucleus, possibly by two pathways: importin 4/7 (Chachami et al. 2009) and importin alpha/beta (Depping et al. 2008). Once in the nucleus HIF-alpha heterodimerizes with HIF-beta (ARNT) (Wang et al. 1995, Jiang et al. 1996, Tian et al. 1997, Gu et al. 1998, Erbel et al. 2003) and recruits CBP and p300 to promoters of target genes (Ebert and Bunn 1998, Kallio et al. 1998, Ema et al. 1999, Gu et al. 2001, Dames et al. 2002, Freedman et al. 2002).

Literature References
PubMed ID Title Journal Year
8663540 Dimerization, DNA binding, and transactivation properties of hypoxia-inducible factor 1 J Biol Chem 1996
9000051 Endothelial PAS domain protein 1 (EPAS1), a transcription factor selectively expressed in endothelial cells Genes Dev 1997
7539918 Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension Proc Natl Acad Sci U S A 1995
9840812 Molecular characterization and chromosomal localization of a third alpha-class hypoxia inducible factor subunit, HIF3alpha Gene Expr 1998
11063749 Molecular mechanism of hypoxia-inducible factor 1alpha -p300 interaction. A leucine-rich interface regulated by a single cysteine J Biol Chem 2001
10202154 Molecular mechanisms of transcription activation by HLF and HIF1alpha in response to hypoxia: their stabilization and redox signal-induced interaction with CBP/p300 EMBO J 1999
18187047 Nuclear translocation of hypoxia-inducible factors (HIFs): involvement of the classical importin alpha/beta pathway Biochim Biophys Acta 2008
9632793 Regulation of transcription by hypoxia requires a multiprotein complex that includes hypoxia-inducible factor 1, an adjacent transcription factor, and p300/CREB binding protein Mol Cell Biol 1998
9822602 Signal transduction in hypoxic cells: inducible nuclear translocation and recruitment of the CBP/p300 coactivator by the hypoxia-inducible factor-1alpha EMBO J 1998
11959977 Structural basis for Hif-1 alpha /CBP recognition in the cellular hypoxic response Proc Natl Acad Sci U S A 2002
14668441 Structural basis for PAS domain heterodimerization in the basic helix--loop--helix-PAS transcription factor hypoxia-inducible factor Proc Natl Acad Sci U S A 2003
11959990 Structural basis for recruitment of CBP/p300 by hypoxia-inducible factor-1 alpha Proc Natl Acad Sci U S A 2002
19788888 Transport of hypoxia-inducible factor HIF-1alpha into the nucleus involves importins 4 and 7 Biochem Biophys Res Commun 2009
Participants
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Cross References
BioModels Database