Regulation of the Drosophila bHLH-PAS protein Sima by hypoxia: functional evidence for homology with mammalian HIF-1 alpha.
Hypoxia inducible factor-1 (HIF-1) is a heterodimeric complex of two basic-helix-loop-helix proteins of the PAS family which is critical for oxygen-dependent expression of many mammalian genes. Regulation is mediated by the alpha subunit (HIF-1 alpha) and sequences from HIF-1 alpha can confer hypoxi...
| Autori principali: | , , , , , , |
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| Natura: | Journal article |
| Lingua: | English |
| Pubblicazione: |
1998
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| _version_ | 1826277458801852416 |
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| author | Bacon, N Wappner, P O'Rourke, J Bartlett, S Shilo, B Pugh, C Ratcliffe, P |
| author_facet | Bacon, N Wappner, P O'Rourke, J Bartlett, S Shilo, B Pugh, C Ratcliffe, P |
| author_sort | Bacon, N |
| collection | OXFORD |
| description | Hypoxia inducible factor-1 (HIF-1) is a heterodimeric complex of two basic-helix-loop-helix proteins of the PAS family which is critical for oxygen-dependent expression of many mammalian genes. Regulation is mediated by the alpha subunit (HIF-1 alpha) and sequences from HIF-1 alpha can confer hypoxia-inducible activity on a Ga14 fusion protein. To analyse conservation of this system of gene regulation between Drosophila and mammalian cells we constructed Ga14 fusions with a series of Drosophila basic-helix-loop-helix PAS (bHLH-PAS) proteins and tested for hypoxia inducibility in transfected Hep3B cells. We found that Ga14 functions with Similar (Sima) but not other Drosophila bHLH-PAS proteins showed inducible activity following exposure to stimuli which classically activate mammalian HIF-1:hypoxia, cobaltous ions, and desferrioxamine. We also found that Sima protein accumulated in Drosophila SL2 cells following hypoxia. Together these findings indicate the existence of functional homologies between Sima and HIF-1 alpha, and that conservation is such as to enable Sima to interact with the hypoxia signal transduction system in mammalian cells. |
| first_indexed | 2024-03-06T23:29:12Z |
| format | Journal article |
| id | oxford-uuid:6b6e4adb-142b-40e1-92f5-65bb8c6eb6f3 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T23:29:12Z |
| publishDate | 1998 |
| record_format | dspace |
| spelling | oxford-uuid:6b6e4adb-142b-40e1-92f5-65bb8c6eb6f32022-03-26T19:04:03ZRegulation of the Drosophila bHLH-PAS protein Sima by hypoxia: functional evidence for homology with mammalian HIF-1 alpha.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:6b6e4adb-142b-40e1-92f5-65bb8c6eb6f3EnglishSymplectic Elements at Oxford1998Bacon, NWappner, PO'Rourke, JBartlett, SShilo, BPugh, CRatcliffe, PHypoxia inducible factor-1 (HIF-1) is a heterodimeric complex of two basic-helix-loop-helix proteins of the PAS family which is critical for oxygen-dependent expression of many mammalian genes. Regulation is mediated by the alpha subunit (HIF-1 alpha) and sequences from HIF-1 alpha can confer hypoxia-inducible activity on a Ga14 fusion protein. To analyse conservation of this system of gene regulation between Drosophila and mammalian cells we constructed Ga14 fusions with a series of Drosophila basic-helix-loop-helix PAS (bHLH-PAS) proteins and tested for hypoxia inducibility in transfected Hep3B cells. We found that Ga14 functions with Similar (Sima) but not other Drosophila bHLH-PAS proteins showed inducible activity following exposure to stimuli which classically activate mammalian HIF-1:hypoxia, cobaltous ions, and desferrioxamine. We also found that Sima protein accumulated in Drosophila SL2 cells following hypoxia. Together these findings indicate the existence of functional homologies between Sima and HIF-1 alpha, and that conservation is such as to enable Sima to interact with the hypoxia signal transduction system in mammalian cells. |
| spellingShingle | Bacon, N Wappner, P O'Rourke, J Bartlett, S Shilo, B Pugh, C Ratcliffe, P Regulation of the Drosophila bHLH-PAS protein Sima by hypoxia: functional evidence for homology with mammalian HIF-1 alpha. |
| title | Regulation of the Drosophila bHLH-PAS protein Sima by hypoxia: functional evidence for homology with mammalian HIF-1 alpha. |
| title_full | Regulation of the Drosophila bHLH-PAS protein Sima by hypoxia: functional evidence for homology with mammalian HIF-1 alpha. |
| title_fullStr | Regulation of the Drosophila bHLH-PAS protein Sima by hypoxia: functional evidence for homology with mammalian HIF-1 alpha. |
| title_full_unstemmed | Regulation of the Drosophila bHLH-PAS protein Sima by hypoxia: functional evidence for homology with mammalian HIF-1 alpha. |
| title_short | Regulation of the Drosophila bHLH-PAS protein Sima by hypoxia: functional evidence for homology with mammalian HIF-1 alpha. |
| title_sort | regulation of the drosophila bhlh pas protein sima by hypoxia functional evidence for homology with mammalian hif 1 alpha |
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