Document Detail

Analysis of the cellular uptake and nuclear delivery of insulin-like growth factor binding protein-3 in human osteosarcoma cells.
MedLine Citation:
PMID:  21520041     Owner:  NLM     Status:  Publisher    
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.
Lucia Micutkova; 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
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-4-25
Journal Detail:
Title:  International journal of cancer. Journal international du cancer     Volume:  -     ISSN:  1097-0215     ISO Abbreviation:  -     Publication Date:  2011 Apr 
Date Detail:
Created Date:  2011-4-26     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0042124     Medline TA:  Int J Cancer     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2011 UICC.
Institute for Biomedical Aging Research, Austrian Academy of Sciences, Rennweg 10, A-6020 Innsbruck, Austria.
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