| First Author | Maltepe E | Year | 2000 |
| Journal | Biochem Biophys Res Commun | Volume | 273 |
| Issue | 1 | Pages | 231-8 |
| PubMed ID | 10873592 | Mgi Jnum | J:354152 |
| Mgi Id | MGI:7731031 | Doi | 10.1006/bbrc.2000.2928 |
| Citation | Maltepe E, et al. (2000) The role of ARNT2 in tumor angiogenesis and the neural response to hypoxia. Biochem Biophys Res Commun 273(1):231-8 |
| abstractText | The Hypoxia-Inducible Factor-1 (HIF-1) activates the transcription of many genes required for cellular and organismal responses to oxygen deprivation. The HIF-1 complex is composed of the ubiquitously expressed basic helix-loop-helix/PAS (bHLH/PAS) proteins HIF-1alpha and Arylhydrocarbon Receptor Nuclear Translocator (ARNT). ARNT2 is a conserved ARNT homolog that is highly expressed in neurons, suggesting that ARNT2/HIF-1alpha heterodimers mediate transcriptional responses to oxygen deprivation in the nervous system. We show here that ARNT2 forms functional HIF complexes in vivo, and that ARNT2 restores hypoxia-induced gene expression to ARNT-deficient ES cells and hepatocytes. Formation of neural ARNT2/HIF-1alpha complexes in Arnt(-/-) ES cell-derived teratocarcinomas may explain why these tumors express VEGF, vascularize and grow efficiently, in contrast to ARNT-deficient hepatomas. Interestingly, all neural cell types studied accumulate both ARNT- and ARNT2-containing HIF complexes. We conclude that ARNT2 forms functional HIF complexes in neurons and plays an integral role in hypoxic responses in the CNS. |
