Retinoblastoma susceptibility gene product pRB activates hypoxia-inducible factor-1 (HIF-1)
Hypoxia-inducible factor-1 alpha (HIF-1) constitutes a regulatory subunit of HIF-1, a major transcriptional activator of genes that coordinate physiological and pathological responses towards hypoxia. In order to identify novel interaction partners of HIF-1 we have applied T7 phage display system an...
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| Hauptverfasser: | , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
10 January 2005
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| In: |
Oncogene
Year: 2005, Jahrgang: 24, Heft: 10, Pages: 1802-1808 |
| ISSN: | 1476-5594 |
| DOI: | 10.1038/sj.onc.1208369 |
| Online-Zugang: | Verlag, Volltext: http://dx.doi.org/10.1038/sj.onc.1208369 Verlag, Volltext: https://www.nature.com/onc/journal/v24/n10/full/1208369a.html 
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| Verfasserangaben: | Andreja Budde, Nicole Schneiderhan-Marra, Gabriele Petersen, Bernhard Brüne |
| Zusammenfassung: | Hypoxia-inducible factor-1 alpha (HIF-1) constitutes a regulatory subunit of HIF-1, a major transcriptional activator of genes that coordinate physiological and pathological responses towards hypoxia. In order to identify novel interaction partners of HIF-1 we have applied T7 phage display system and identified a domain inherent in the retinoblastoma protein (pRB). The interaction between pRB and HIF-1 was confirmed by in vitro experiments and in transfected cells. Thereby, an HIF-1 domain spanning amino acids 530-694 was mapped to be required for pRB binding. Overexpression of pRB provoked transcriptional activation of HIF-1 under normoxia. Furthermore, the domain of pRB identified to bind HIF-1 in vitro is sufficient to cause HIF-1 transcriptional activation with the further notion that phosphorylation deficient pRB shows stronger HIF-1 transactivation. Using ChIP analysis, we show that HIF-1 responsive elements (HREs) are precipitated using -pRB antibodies. Additionally, a functional interaction between pRB and HIF-1 is confirmed by showing that HIF-1 reverses the transcription repressor function of pRB. |
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| Beschreibung: | Gesehen am 24.05.2017 |
| Beschreibung: | Online Resource |
| ISSN: | 1476-5594 |
| DOI: | 10.1038/sj.onc.1208369 |