p14ARF induces the relocation of HDM2 and p53 to extranucleolar sites that are targeted by PML bodies and proteasomes.
BACKGROUND
p14ARF is a protein product of the alternative reading frame of the human INK4a locus. It functions as a tumor suppressor protein. p14ARF suppresses growth through p53-dependent and p53-independent pathways.


RESULTS
p14ARF protein localizes primarily to the nucleoli. Here we show that in transfected cells p14ARF also appears in Hsp70 positive extranucleolar inclusions. The formation of p14ARF inclusions induces the parallel re-localization p53 and HDM2 to these sites that are also targeted by PML bodies and proteasomes.


CONCLUSIONS
Our data show that co-localization between p53, HDM2 and p14ARF occurs at extranucleolar sites. Accumulation of PML and proteasomes at these sites suggest that the components of the nuclear inclusions are targeted for proteasome-mediated degradation.
Kashuba
Elena
E
Microbiology and Tumor Biology Center (MTC), Karolinska Institute, S 171 77, Stockholm, Sweden. Elena.Kashuba@mtc.ki.se
Mattsson
Karin
K
Klein
George
G
Szekely
Laszlo
L
D000818:Animals; D002460:Cell Line; D002466:Cell Nucleolus / Q000737:chemistry; D022003:Cell Nucleus Structures / Q000737:chemistry* / Q000378:metabolism; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D018840:HSP70 Heat-Shock Proteins / Q000032:analysis / Q000378:metabolism; D006801:Humans; D051379:Mice; D008856:Microscopy, Fluorescence; D009097:Multienzyme Complexes / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000032:analysis; D009687:Nuclear Proteins / Q000032:analysis* / Q000378:metabolism; D000071156:Promyelocytic Leukemia Protein; D046988:Proteasome Endopeptidase Complex; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000378:metabolism; D051736:Proto-Oncogene Proteins c-mdm2; D014157:Transcription Factors / Q000032:analysis; D014162:Transfection; D025803:Tumor Suppressor Protein p14ARF / Q000032:analysis* / Q000235:genetics / Q000502:physiology; D016159:Tumor Suppressor Protein p53 / Q000032:analysis / Q000378:metabolism; D025521:Tumor Suppressor Proteins
D018840:HSP70 Heat-Shock Proteins; D009097:Multienzyme Complexes; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; C513293:Pml protein, mouse; D000071156:Promyelocytic Leukemia Protein; D011518:Proto-Oncogene Proteins; D014157:Transcription Factors; D025803:Tumor Suppressor Protein p14ARF; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; C070576:PML protein, human; C497206:MDM2 protein, human; C497207:Mdm2 protein, mouse; D051736:Proto-Oncogene Proteins c-mdm2; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex