PMID- 16882692
OWN - NLM
STAT- MEDLINE
DCOM- 20061026
LR  - 20091119
IS  - 0021-9533 (Print)
IS  - 0021-9533 (Linking)
VI  - 119
IP  - Pt 16
DP  - 2006 Aug 15
TI  - Casein kinase 2 inhibition decreases hypoxia-inducible factor-1 activity under 
      hypoxia through elevated p53 protein level.
PG  - 3351-62
AB  - HIF-1 (hypoxia-inducible factor-1) is the main transcription factor involved in 
      the adaptation of cells to hypoxia. In addition to regulation of HIF-1alpha 
      protein level, HIF-1 activity is also enhanced by several pathways involving 
      asparagine hydroxylation and phosphorylation. Here, we investigated the 
      relationship between casein kinase 2 (CK2), p53 and HIF-1. An increase in p53 
      protein level and transcriptional activity was observed when CK2 was inhibited by 
      different inhibitors under normoxia and hypoxia. This increase was in parallel 
      with a decrease in HIF-1 activity without changes in HIF-1alpha protein level, 
      indicating a regulation of its transcriptional activity. Similar results were 
      obtained using CK2alpha siRNA. Ectopic overexpression of p53 also led to an 
      inhibition of HIF-1 activity. Conversely, CK2 inhibition had no effect in 
      p53-null cells indicating that the inhibitory effect of CK2 inhibitors requires 
      the presence of p53. p53 activity was not required because overexpression of a 
      p53 mutated in its DNA-binding domain exerted the same effect as wild-type p53 
      and because the effect of CK2 inhibitors was still observed when p53 activity was 
      inhibited by pifithrin-alpha. Since CK2 activity is increased in hypoxic 
      conditions, this process provides one more mechanism to ensure enhanced HIF-1 
      activity under such conditions.
FAU - Hubert, Antoine
AU  - Hubert A
AD  - Laboratory of Biochemistry and Cellular Biology, University of Namur, 61 Rue de 
      Bruxelles, 5000 Namur, Belgium.
FAU - Paris, Sebastien
AU  - Paris S
FAU - Piret, Jean-Pascal
AU  - Piret JP
FAU - Ninane, Noelle
AU  - Ninane N
FAU - Raes, Martine
AU  - Raes M
FAU - Michiels, Carine
AU  - Michiels C
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20060801
PL  - England
TA  - J Cell Sci
JT  - Journal of cell science
JID - 0052457
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - EC 2.7.11.1 (Casein Kinase II)
SB  - IM
MH  - Carcinoma, Hepatocellular/metabolism/pathology
MH  - Casein Kinase II/*antagonists & inhibitors
MH  - Cell Hypoxia
MH  - Cells, Cultured
MH  - Enzyme Inhibitors/pharmacology
MH  - HeLa Cells/metabolism
MH  - Humans
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/genetics/*metabolism
MH  - Liver Neoplasms/metabolism/pathology
MH  - Transcription, Genetic
MH  - Tumor Suppressor Protein p53/genetics/*metabolism
EDAT- 2006/08/03 09:00
MHDA- 2006/10/27 09:00
CRDT- 2006/08/03 09:00
PHST- 2006/08/03 09:00 [pubmed]
PHST- 2006/10/27 09:00 [medline]
PHST- 2006/08/03 09:00 [entrez]
AID - jcs.03069 [pii]
AID - 10.1242/jcs.03069 [doi]
PST - ppublish
SO  - J Cell Sci. 2006 Aug 15;119(Pt 16):3351-62. doi: 10.1242/jcs.03069. Epub 2006 Aug 
      1.