Analysis of the cellular uptake and nuclear delivery of insulin-like growth factor binding protein-3 in human osteosarcoma cells

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2012
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Micutkova, Lucia
Hermann, Martin
Offterdinger, Martin
Hess, Michael W.
Matscheski, Andrea
Pircher, Haymo
Mück, Christoph
Ebner, Hannes-Leonhard
Laich, Andreas
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International Journal of Cancer. 2012, 130(7), pp. 1544-1557. ISSN 0020-7136. eISSN 1097-0215. Available under: doi: 10.1002/ijc.26149
Zusammenfassung

Insulin-like growth factor (IGF) binding protein-3 (IGFBP-3) regulates cell proliferation and survival by extracellular interaction and inactivation of the growth factor IGF-I. Beyond that, IGF-independent actions mediated by intracellular IGFBP-3 including nuclear-IGFBP-3, have also been described. We here show, using both confocal and electron microscopy and cell fractionation, that the extracellular addition of IGFBP-3 to living cells results in rapid uptake and nuclear delivery of IGFBP-3, by yet partly unknown mechanisms. IGFBP-3 is internalized through a dynamin-dependent pathway, traffics through endocytic compartments and is finally delivered into the nucleus. We observed docking of IGFBP-3 containing structures to the nuclear envelope and found IGFBP-3 containing dot-like structures to permeate the nuclear envelope. In summary, our findings establish the pathway by which this tumor suppressor protein is delivered from extracellular space to the nucleus.

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ISO 690MICUTKOVA, Lucia, Martin HERMANN, Martin OFFTERDINGER, Michael W. HESS, Andrea MATSCHESKI, Haymo PIRCHER, Christoph MÜCK, Hannes-Leonhard EBNER, Andreas LAICH, Elisa FERRANDO-MAY, Werner ZWERSCHKE, Lukas A. HUBER, Pidder JANSEN-DÜRR, 2012. Analysis of the cellular uptake and nuclear delivery of insulin-like growth factor binding protein-3 in human osteosarcoma cells. In: International Journal of Cancer. 2012, 130(7), pp. 1544-1557. ISSN 0020-7136. eISSN 1097-0215. Available under: doi: 10.1002/ijc.26149
BibTex
@article{Micutkova2012-04-01Analy-18223,
  year={2012},
  doi={10.1002/ijc.26149},
  title={Analysis of the cellular uptake and nuclear delivery of insulin-like growth factor binding protein-3 in human osteosarcoma cells},
  number={7},
  volume={130},
  issn={0020-7136},
  journal={International Journal of Cancer},
  pages={1544--1557},
  author={Micutkova, Lucia and Hermann, Martin and Offterdinger, Martin and Hess, Michael W. and Matscheski, Andrea and Pircher, Haymo and Mück, Christoph and Ebner, Hannes-Leonhard and Laich, Andreas and Ferrando-May, Elisa and Zwerschke, Werner and Huber, Lukas A. and Jansen-Dürr, Pidder}
}
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