Pex19p dampens the p19ARF-p53-p21WAF1 tumor suppressor pathway.
We isolated a 33-kDa protein, Pex19p/HK33/HsPXF, as a p19ARF-binding protein in a yeast two-hybrid screen. We demonstrate here that Pex19p interacts with p19ARF in the cell cytoplasm and excludes p19ARF from the nucleus, leading to a concurrent inactivation of p53 function. Down-regulation of Pex19p by its antisense expression resulted in increased levels of p19ARF, increased p53 function, and a p53/p21WAF1-mediated senescence-like cell cycle arrest. The data demonstrated a novel mechanism of down-regulation of the p19ARF-p53 pathway.
Chugai Research Institute for Molecular Medicine, 153-2 Nagai, Niihari-Mura, Ibaraki 300-41, Japan.
T
T
Sugihara
S C
SC
Kaul
J
J
Kato
R R
RR
Reddel
H
H
Nomura
R
R
Wadhwa
D016475:3T3 Cells; D000818:Animals; D019556:COS Cells; D002453:Cell Cycle; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D017930:Genes, Reporter; D016147:Genes, Tumor Suppressor; D000882:Haplorhini; D008565:Membrane Proteins / Q000378:metabolism* / Q000502:physiology*; D051379:Mice; D016376:Oligonucleotides, Antisense / Q000378:metabolism; D010641:Phenotype; D010957:Plasmids / Q000378:metabolism; D011233:Precipitin Tests; D011485:Protein Binding; D011506:Proteins / Q000378:metabolism*; D025803:Tumor Suppressor Protein p14ARF; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D020798:Two-Hybrid System Techniques
C493957:Cdkn1a protein, mouse; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D018076:DNA, Complementary; D008565:Membrane Proteins; D016376:Oligonucleotides, Antisense; D011506:Proteins; D025803:Tumor Suppressor Protein p14ARF; D016159:Tumor Suppressor Protein p53