PMID- 15674338 OWN - NLM STAT- MEDLINE DCOM- 20050324 LR - 20081121 IS - 0950-9232 (Print) IS - 0950-9232 (Linking) VI - 24 IP - 10 DP - 2005 Mar 3 TI - Retinoblastoma susceptibility gene product pRB activates hypoxia-inducible factor-1 (HIF-1). PG - 1802-8 AB - Hypoxia-inducible factor-1 alpha (HIF-1alpha) 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-1alpha we have applied T7 phage display system and identified a domain inherent in the retinoblastoma protein (pRB). The interaction between pRB and HIF-1alpha was confirmed by in vitro experiments and in transfected cells. Thereby, an HIF-1alpha domain spanning amino acids 530-694 was mapped to be required for pRB binding. Overexpression of pRB provoked transcriptional activation of HIF-1alpha under normoxia. Furthermore, the domain of pRB identified to bind HIF-1alpha in vitro is sufficient to cause HIF-1alpha transcriptional activation with the further notion that phosphorylation deficient pRB shows stronger HIF-1alpha transactivation. Using ChIP analysis, we show that HIF-1alpha responsive elements (HREs) are precipitated using alpha-pRB antibodies. Additionally, a functional interaction between pRB and HIF-1alpha is confirmed by showing that HIF-1alpha reverses the transcription repressor function of pRB. FAU - Budde, Andreja AU - Budde A AD - Department of Medicine IV-Experimental Division, Faculty of Medicine, University of Erlangen-Nurnberg, 91054 Erlangen, Germany. FAU - Schneiderhan-Marra, Nicole AU - Schneiderhan-Marra N FAU - Petersen, Gabriele AU - Petersen G FAU - Brune, Bernhard AU - Brune B LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Oncogene JT - Oncogene JID - 8711562 RN - 0 (Cell Cycle Proteins) RN - 0 (DNA-Binding Proteins) RN - 0 (E2F Transcription Factors) RN - 0 (HIF1A protein, human) RN - 0 (Hypoxia-Inducible Factor 1, alpha Subunit) RN - 0 (Retinoblastoma Protein) RN - 0 (Transcription Factors) SB - IM MH - Amino Acid Sequence MH - Cell Cycle Proteins/physiology MH - DNA-Binding Proteins/physiology MH - E2F Transcription Factors MH - Humans MH - Hypoxia-Inducible Factor 1, alpha Subunit MH - Molecular Sequence Data MH - Response Elements/physiology MH - Retinoblastoma Protein/chemistry/*physiology MH - Transcription Factors/chemistry/*physiology MH - Transcriptional Activation EDAT- 2005/01/28 09:00 MHDA- 2005/03/25 09:00 CRDT- 2005/01/28 09:00 PHST- 2005/01/28 09:00 [pubmed] PHST- 2005/03/25 09:00 [medline] PHST- 2005/01/28 09:00 [entrez] AID - 1208369 [pii] AID - 10.1038/sj.onc.1208369 [doi] PST - ppublish SO - Oncogene. 2005 Mar 3;24(10):1802-8. doi: 10.1038/sj.onc.1208369.