Retinoblastoma susceptibility gene product pRB activates hypoxia-inducible factor-1 (HIF-1)

• Verfasst von: Budde, Andreja [VerfasserIn]
• Verfasst von: Petersen, Gabriele [VerfasserIn]
• Titel: Retinoblastoma susceptibility gene product pRB activates hypoxia-inducible factor-1 (HIF-1)
• Verf.angabe: Andreja Budde, Nicole Schneiderhan-Marra, Gabriele Petersen, Bernhard Brüne
• Umfang: 7 S.
• Fussnoten: Gesehen am 24.05.2017
• Titel Quelle: Enthalten in: Oncogene
• Jahr Quelle: 2005
• Band/Heft Quelle: 24(2005), 10, S. 1802-1808
• ISSN Quelle: 1476-5594
• DOI: doi:10.1038/sj.onc.1208369
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1558994629

Abstract

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, afunctional interaction between pRB and HIF-1 is confirmed by showing that HIF-1 reverses the transcription repressor function of pRB.