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p14ARF induces the relocation of HDM2 and p53 to extranucleolar sites that are targeted by PML bodies and proteasomes.

Kashuba E, Mattsson K, Klein G, Szekely L - Mol. Cancer (2003)

Bottom Line: 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.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Microbiology and Tumor Biology Center (MTC), Karolinska Institute, S 171 77, Stockholm, Sweden. Elena.Kashuba@mtc.ki.se

ABSTRACT

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.

Conclusion: 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.

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PML bodies are randomly scattered in nuclei where pBabe-p14ARF exclusively localized to nucleoli (top row) but gradually associate with the p14ARF positive extranucleolar inclusions in parallel with their expansion (2nd–5th raw) in MCF7 cells. p14ARF positive nuclear inclusions are denoted by hollow arrowheads and nucleoli by full arrowheads. Green – p14ARF, red – PML protein, blue – DNA-staining.
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Figure 3: PML bodies are randomly scattered in nuclei where pBabe-p14ARF exclusively localized to nucleoli (top row) but gradually associate with the p14ARF positive extranucleolar inclusions in parallel with their expansion (2nd–5th raw) in MCF7 cells. p14ARF positive nuclear inclusions are denoted by hollow arrowheads and nucleoli by full arrowheads. Green – p14ARF, red – PML protein, blue – DNA-staining.

Mentions: After p14ARF transfection, we observed that PML bodies were re-distributed to the p14ARF nuclear inclusions (Figure 3). PML and p14ARF proteins showed a high level of co-localization. However, PML protein was not detected in the nucleoli that contained p14ARF protein. Here we demonstrated a striking difference in the properties of the nucleolar p14ARF and p14ARF that formed extranucleolar inclusions.


p14ARF induces the relocation of HDM2 and p53 to extranucleolar sites that are targeted by PML bodies and proteasomes.

Kashuba E, Mattsson K, Klein G, Szekely L - Mol. Cancer (2003)

PML bodies are randomly scattered in nuclei where pBabe-p14ARF exclusively localized to nucleoli (top row) but gradually associate with the p14ARF positive extranucleolar inclusions in parallel with their expansion (2nd–5th raw) in MCF7 cells. p14ARF positive nuclear inclusions are denoted by hollow arrowheads and nucleoli by full arrowheads. Green – p14ARF, red – PML protein, blue – DNA-staining.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC153488&req=5

Figure 3: PML bodies are randomly scattered in nuclei where pBabe-p14ARF exclusively localized to nucleoli (top row) but gradually associate with the p14ARF positive extranucleolar inclusions in parallel with their expansion (2nd–5th raw) in MCF7 cells. p14ARF positive nuclear inclusions are denoted by hollow arrowheads and nucleoli by full arrowheads. Green – p14ARF, red – PML protein, blue – DNA-staining.
Mentions: After p14ARF transfection, we observed that PML bodies were re-distributed to the p14ARF nuclear inclusions (Figure 3). PML and p14ARF proteins showed a high level of co-localization. However, PML protein was not detected in the nucleoli that contained p14ARF protein. Here we demonstrated a striking difference in the properties of the nucleolar p14ARF and p14ARF that formed extranucleolar inclusions.

Bottom Line: 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.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Microbiology and Tumor Biology Center (MTC), Karolinska Institute, S 171 77, Stockholm, Sweden. Elena.Kashuba@mtc.ki.se

ABSTRACT

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.

Conclusion: 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.

Show MeSH
Related in: MedlinePlus