PMID- 11382768
OWN - NLM
STAT- MEDLINE
DCOM- 20010823
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 276
IP  - 30
DP  - 2001 Jul 27
TI  - The p14ARF tumor suppressor protein facilitates nucleolar sequestration of 
      hypoxia-inducible factor-1alpha (HIF-1alpha ) and inhibits HIF-1-mediated 
      transcription.
PG  - 28421-9
AB  - Oncogenic alterations can influence tumor cell survival partly by affecting the 
      activity of the hypoxia-inducible factor-1 (HIF-1) transcription factor. The 
      alpha subunit of HIF-1 was found to be frequently overexpressed in advanced 
      tumors, which was proposed to help the adaptation of tumor cells to hypoxia. Here 
      we show that an important tumor suppressor protein, p14ARF (alternative reading 
      frame product of the INK4A locus) can directly inhibit the transcriptional 
      activity of HIF-1 by sequestering its alpha subunit into the nucleolus. The 
      interaction requires neither p53 nor HDM2. This is one of the first reports that 
      describe the interaction of p14ARF with a protein besides HDM2, which may define 
      a p53-independent tumor suppressor activity for p14ARF.
FAU - Fatyol, K
AU  - Fatyol K
AD  - Department of Biochemistry, Loma Linda University, Loma Linda, California 92350, 
      USA. kfatyol@hotmail.com
FAU - Szalay, A A
AU  - Szalay AA
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20010529
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Cyclin-Dependent Kinase Inhibitor p16)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (HIF1A protein, human)
RN  - 0 (Hif1a protein, mouse)
RN  - 0 (Hypoxia-Inducible Factor 1)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Proteins)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Transcription Factors)
RN  - 0 (Tumor Suppressor Protein p14ARF)
RN  - EC 2.3.2.27 (MDM2 protein, human)
RN  - EC 2.3.2.27 (Mdm2 protein, mouse)
RN  - EC 2.3.2.27 (Proto-Oncogene Proteins c-mdm2)
SB  - IM
MH  - Active Transport, Cell Nucleus
MH  - Animals
MH  - Blotting, Western
MH  - Cell Cycle
MH  - Cell Nucleus/*metabolism
MH  - Cyclin-Dependent Kinase Inhibitor p16/genetics
MH  - DNA-Binding Proteins/antagonists & inhibitors/*metabolism
MH  - Flow Cytometry
MH  - Fluorescent Antibody Technique, Indirect
MH  - Genes, p53/genetics
MH  - Humans
MH  - Hypoxia-Inducible Factor 1
MH  - Hypoxia-Inducible Factor 1, alpha Subunit
MH  - Mice
MH  - Microscopy, Fluorescence
MH  - Nuclear Proteins/antagonists & inhibitors/*metabolism
MH  - Plasmids/metabolism
MH  - Precipitin Tests
MH  - Protein Binding
MH  - Protein Structure, Tertiary
MH  - Proteins/metabolism/*physiology
MH  - Proto-Oncogene Proteins/metabolism
MH  - Proto-Oncogene Proteins c-mdm2
MH  - *Transcription Factors
MH  - *Transcription, Genetic
MH  - Transfection
MH  - Tumor Cells, Cultured
MH  - Tumor Suppressor Protein p14ARF
EDAT- 2001/05/31 10:00
MHDA- 2001/08/24 10:01
CRDT- 2001/05/31 10:00
PHST- 2001/05/31 10:00 [pubmed]
PHST- 2001/08/24 10:01 [medline]
PHST- 2001/05/31 10:00 [entrez]
AID - S0021-9258(19)31654-0 [pii]
AID - 10.1074/jbc.M102847200 [doi]
PST - ppublish
SO  - J Biol Chem. 2001 Jul 27;276(30):28421-9. doi: 10.1074/jbc.M102847200. Epub 2001 
      May 29.