HIF-1 and HIF-2: Working alone or together in hypoxia?

Journal of Clinical Investigation

Volumn 117, Issue 4, 2007, Pages 862-865

  Ratcliffe, Peter J ^a  

^a UNIVERSITY OF OXFORD   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

ERYTHROPOIETIN; HYPOXIA INDUCIBLE FACTOR 1ALPHA; HYPOXIA INDUCIBLE FACTOR 2ALPHA; OXYGENASE; PROTEIN BNIP3;

ANEMIA; ANGIOGENESIS; CELL DIFFERENTIATION; CELL MOTILITY; CELL TYPE; ERYTHROPOIESIS; GENE INACTIVATION; GENETIC TRANSCRIPTION; HUMAN; HYDROXYLATION; HYPOXIA; NONHUMAN; NOTE; PHENOTYPE; PRIORITY JOURNAL; PROTEIN DEGRADATION; PROTEIN EXPRESSION;

BASIC HELIX-LOOP-HELIX TRANSCRIPTION FACTORS; ERYTHROPOIETIN; GENE EXPRESSION REGULATION; HUMANS; HYPOXIA-INDUCIBLE FACTOR 1, ALPHA SUBUNIT; PROTEIN ISOFORMS; TRANSCRIPTION, GENETIC;

EID: 34147170511     PISSN: 00219738     EISSN: 15588238     Source Type: Journal    
DOI: 10.1172/JCI31750     Document Type: Note

References (21)

1. 2 tension. Proc. Natl. Acad. Sci. U. S. A. 92:5510-5514.
2. Maxwell, P.H., Pugh, C.W., and Ratcliffe, P.J. 1993. Inducible operation of the erythropoietin 3′ enhancer in multiple cell lines: evidence for a widespread oxygen sensing mechanism. Proc. Natl. Acad. Sci. U. S. A. 90:2423-2427.
3. 2-regulated gene expression. FASEB J. 16:1151-1162.
4. Schofield, C.J., and Ratcliffe, P.J. 2004. Oxygen sensing by HIF hydroxylases. Nat. Rev. Mol. Cell Biol. 5:343-354.
5. Rosenberger, C., et al. 2002. Expression of hypoxia-inducible factor-1a and -2a in hypoxic and ischemic rat kidneys. J. Am. Soc. Nephrol. 13:1721-1732.
6. Wiesener, M.S., et al. 2002. Widespread, hypoxia-inducible expression of HIF-2a in distinct cell populations of different organs. FASEB J. 17:271-273.
7. Holmquist-Mengelbier, L., et al. 2006. Recruitment of HIF-1a and HIF-2a to common target genes is differentially regulated in neuroblastoma: HIF-2a promotes an aggressive phenotype. Cancer Cell. 10:413-423.
8. Rankin, E.B., et al. 2007. Hypoxia-inducible factor-2 (HIF-2) regulates hepatic erythropoietin in vivo. J. Clin. Invest. 117:1068-1077. doi:10.1172/JCI30117.
9. Hu, C.-J., Wang, L.-Y., Chodosh, L.A., Keith, B., and Simon, M.C. 2003. Differential roles of hypoxia-inducible factor 1a (HIF-1a) and HIF-2a in hypoxic gene regulation. Mol. Cell. Biol. 23:9361-9374.
10. Kaelin, W.G. 2002. Molecular basis of the vhl hereditary cancer syndrome. Nat. Rev. Cancer. 2:673-682.
11. Covello, K.L., Simon, M.C., and Keith, B. 2005. Targeted replacement of hypoxia-inducible factor-1alpha by a hypoxia-inducible factor-2alpha knock-in allele promotes tumor growth. Cancer Res. 65:2277-2286.
12. Covello, K.L., et al. 2006. HIF-2alpha regulates Oct-4: effects of hypoxia on stem cell function, embryonic development, and tumor growth. Genes Dev. 20:557-570.
13. Kondo, K., Kico, J., Nakamura, E., Lechpammer, M., and Kaelin, W.G.J. 2002. Inhibition of HIF is necessary for tumor suppression by the von Hippel-Lindau protein. Cancer Cell. 1:237-246.
14. Raval, R.R., et al. 2005. Contrasting properties of hypoxia-inducible factor 1 (HIF-1) and HIF-2 in von Hippel-Lindau-associated renal cell carcinoma. Mol. Cell. Biol. 25:5675-5686.
15. Park, S.-K., et al. 2003. Hypoxia-induced gene expression occurs solely through the action of hypoxiainducible factor 1a (HIF-1a): role of cytoplasmic trapping of HIF-2a. Mol. Cell. Biol. 23:4959-4971.
16. Hu, C.J., et al. 2006. Differential regulation of the transcriptional activities of hypoxia-inducible factor 1 alpha (HIF-1α) and HIF-2α in stem cells. Mol. Cell. Biol. 26:3514-3526.
17. Yu, A.Y., et al. 1999. Impaired physiological responses to chronic hypoxia in mice partially deficient for hypoxia-inducible factor 1α. J. Clin. Invest. 103:691-696.
18. Scortegagna, M., et al. 2005. HIF-2alpha regulates murine hematopoietic development in an erythropoietin-dependent manner. Blood. 105:3133-3140.
19. Warnecke, C., et al. 2004. Differentiating the functional role of hypoxia-inducible factor (HIF)-1alpha and HIF-2alpha (EPAS-1) by the use of RNA interference: erythropoietin is a HIF-2alpha target gene in HepB and Kelly cells. FASEB J. 18:1462-1464.
20. Maxwell, P.H., et al. 1993. Identification of the renal erythropoietin-producing cells using transgenic mice. Kidney Int. 44:1149-1162.
21. Da Silva, J.L., et al. 1990. Tumour cells are the site of erythropoietin synthesis in human renal cancers associated with polycythemia. Blood. 75:577-582.