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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.

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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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Related in: MedlinePlus

HDM2 protein (red) is re-distributed to pBabe-p14ARF (green) nuclear inclusions, but not to nucleoli that contain p14ARF in MCF7 cells. DNA staining is shown in blue.
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Figure 5: HDM2 protein (red) is re-distributed to pBabe-p14ARF (green) nuclear inclusions, but not to nucleoli that contain p14ARF in MCF7 cells. DNA staining is shown in blue.

Mentions: One of the stress response proteins, Hsp70, is often redistributed both to the nucleus and to the nucleolus during periods of cell stress. Here we show that in those p14ARF transfected cells where p14ARF accumulated in the extranucleolar inclusions Hsp70 was targeted to the nucleus and showed a high grade of co-localization with p14ARF extranuclear inclusions (Figure 5). No Hsp70 accumulation was observed when the transfected p14ARF gathered in the nucleolus.


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)

HDM2 protein (red) is re-distributed to pBabe-p14ARF (green) nuclear inclusions, but not to nucleoli that contain p14ARF in MCF7 cells. DNA staining is shown in blue.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 5: HDM2 protein (red) is re-distributed to pBabe-p14ARF (green) nuclear inclusions, but not to nucleoli that contain p14ARF in MCF7 cells. DNA staining is shown in blue.
Mentions: One of the stress response proteins, Hsp70, is often redistributed both to the nucleus and to the nucleolus during periods of cell stress. Here we show that in those p14ARF transfected cells where p14ARF accumulated in the extranucleolar inclusions Hsp70 was targeted to the nucleus and showed a high grade of co-localization with p14ARF extranuclear inclusions (Figure 5). No Hsp70 accumulation was observed when the transfected p14ARF gathered in the nucleolus.

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