| Autor: |
Laich, A., Matscheski, A., Mück, C., Ferrando-May, E., Pircher, H., Ebner, H.L., Micutkova, L., Huber, L.A., Hermann, M., Offerdinger, M., Hess, M.W., Jansen-Dürr, P., Zwerschke, W.. |
| Jazyk: |
angličtina |
| Rok vydání: |
2010 |
| Předmět: |
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| Popis: |
Insulin-like growth factor (IGF) binding protein-3 (IGFBP-3) is an important regulator of cell proliferation and survival, which plays an important role in a variety of epithelial cancers, including prostate cancer, cervical cancer and breast cancer. IGFBP-3 was described as a tumor suppressor in the prostate and identified as a functional cellular target for the E7 oncoprotein of human papillomaviruses. IGFBP-3 interacts with IGF-I outside the cell; however, IGF-independent actions of IGFBP-3 were also described which are mediated by intracellular IGFBP-3, including nuclear IGFBP-3. The mechanisms by which extracellular proteins can reach the nucleus are still largely unknown. We show here that the addition of IGFBP-3 to living cells results in the rapid appearance of nuclear IGFBP-3 by confocal microscopy of IGFBP-3 uptake in live cells, supported by electron microscopy and cell fractionation studies. 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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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