PMID- 14992692
OWN - NLM
STAT- MEDLINE
DCOM- 20041026
LR  - 20181113
IS  - 1470-8728 (Electronic)
IS  - 0264-6021 (Print)
IS  - 0264-6021 (Linking)
VI  - 380
IP  - Pt 1
DP  - 2004 May 15
TI  - p300 relieves p53-evoked transcriptional repression of hypoxia-inducible factor-1 
      (HIF-1).
PG  - 289-95
AB  - HIF-1 (hypoxia-inducible factor-1), a heterodimeric transcription factor 
      comprising HIF-1alpha and HIF-1beta subunits, serves as a key regulator of 
      metabolic adaptation to hypoxia. HIF-1 activity largely increases during hypoxia 
      by attenuating pVHL (von Hippel-Lindau protein)-dependent ubiquitination and 
      subsequent 26 S-proteasomal degradation of HIF-1alpha. Besides HIF-1, the 
      transcription factor and tumour suppressor p53 accumulates and is activated under 
      conditions of prolonged/severe hypoxia. Recently, the interaction between p53 and 
      HIF-1alpha was reported to evoke HIF-1alpha degradation. Destruction of 
      HIF-1alpha by p53 was corroborated in the present study by using pVHL-deficient 
      RCC4 (renal carcinoma) cells, supporting the notion of a pVHL-independent 
      degradation process. In addition, low p53 expression repressed HIF-1 
      transactivation without affecting HIF-1alpha protein amount. Establishing that 
      p53-evoked inhibition of HIF-1 reporter activity was relieved upon 
      co-transfection of p300 suggested competition between p53 and HIF-1 for limiting 
      amounts of the shared co-activator p300. This assumption was confirmed by showing 
      competitive binding of in vitro transcription/translation-generated p53 and 
      HIF-1alpha to the CH1 domain of p300 in vitro. We conclude that low p53 
      expression attenuates HIF-1 transactivation by competing for p300, whereas high 
      p53 expression destroys the HIF-1alpha protein and thereby eliminates HIF-1 
      reporter activity. Thus once p53 becomes activated under conditions of severe 
      hypoxia/anoxia, it contributes to terminating HIF-1 responses.
FAU - Schmid, Tobias
AU  - Schmid T
AD  - Department of Cell Biology, Faculty of Biology, University of Kaiserslautern, 
      Erwin Schroedinger Strasse 13/4, 67663 Kaiserslautern, Germany.
FAU - Zhou, Jie
AU  - Zhou J
FAU - Kohl, Roman
AU  - Kohl R
FAU - Brune, Bernhard
AU  - Brune B
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Biochem J
JT  - The Biochemical journal
JID - 2984726R
RN  - 0 (HIF1A protein, human)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Macromolecular Substances)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Trans-Activators)
RN  - 0 (Transcription Factors)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - 0 (Tumor Suppressor Proteins)
RN  - EC 1.13.12.- (Luciferases)
RN  - EC 2.3.2.27 (Ubiquitin-Protein Ligases)
RN  - EC 2.3.2.27 (Von Hippel-Lindau Tumor Suppressor Protein)
RN  - EC 3.4.- (Peptide Hydrolases)
RN  - EC 3.4.25.1 (Proteasome Endopeptidase Complex)
RN  - EC 3.4.99.- (ATP dependent 26S protease)
RN  - EC 6.3.2.- (VHL protein, human)
SB  - IM
MH  - Binding Sites
MH  - Binding, Competitive
MH  - Carcinoma/pathology
MH  - Carcinoma, Renal Cell/pathology
MH  - Cell Hypoxia
MH  - Cell Line, Tumor
MH  - Colonic Neoplasms/pathology
MH  - Genes, Reporter
MH  - Genes, p53
MH  - Humans
MH  - Hypoxia-Inducible Factor 1, alpha Subunit
MH  - Kidney Neoplasms/pathology
MH  - Luciferases/biosynthesis/genetics
MH  - Macromolecular Substances
MH  - Nuclear Proteins/*metabolism
MH  - Peptide Hydrolases/metabolism
MH  - *Proteasome Endopeptidase Complex
MH  - Protein Binding
MH  - Protein Interaction Mapping
MH  - Protein Structure, Tertiary
MH  - Recombinant Fusion Proteins/biosynthesis/genetics
MH  - Trans-Activators/*metabolism
MH  - Transcription Factors/*biosynthesis/genetics
MH  - Transcriptional Activation/*physiology
MH  - Transfection
MH  - Tumor Suppressor Protein p53/*metabolism
MH  - Tumor Suppressor Proteins/deficiency
MH  - Ubiquitin-Protein Ligases/deficiency
MH  - Von Hippel-Lindau Tumor Suppressor Protein
PMC - PMC1224165
EDAT- 2004/03/03 05:00
MHDA- 2004/10/27 09:00
PMCR- 2004/11/15
CRDT- 2004/03/03 05:00
PHST- 2004/03/01 00:00 [accepted]
PHST- 2004/02/19 00:00 [revised]
PHST- 2003/08/26 00:00 [received]
PHST- 2004/03/03 05:00 [pubmed]
PHST- 2004/10/27 09:00 [medline]
PHST- 2004/03/03 05:00 [entrez]
PHST- 2004/11/15 00:00 [pmc-release]
AID - BJ20031299 [pii]
AID - 10.1042/BJ20031299 [doi]
PST - ppublish
SO  - Biochem J. 2004 May 15;380(Pt 1):289-95. doi: 10.1042/BJ20031299.