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SDF-1 chemokine signalling modulates the apoptotic responses to iron deprivation of clathrin-depleted DT40 cells.



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Pance, Alena 
Morrissey-Wettey, Frank R 
Craig, Helen 
Downing, Alison 
Talbot, Richard 


We have previously deleted both endogenous copies of the clathrin heavy-chain gene in the chicken pre B-cell-line DT40 and replaced them with clathrin under the control of a tetracycline-regulatable promoter (Tet-Off). The originally derived cell-line DKO-S underwent apoptosis when clathrin expression was repressed. We have also described a cell-line DKO-R derived from DKO-S cells that was less sensitive to clathrin-depletion. Here we show that the restriction of transferrin uptake, resulting in iron deprivation, is responsible for the lethal consequence of clathrin-depletion. We further show that the DKO-R cells have up-regulated an anti-apoptotic survival pathway based on the chemokine SDF-1 and its receptor CXCR4. Our work clarifies several puzzling features of clathrin-depleted DT40 cells and reveals an example of how SDF-1/CXCR4 signalling can abrogate pro-apoptotic pathways and increase cell survival. We propose that the phenomenon described here has implications for the therapeutic approach to a variety of cancers.



Animals, Apoptosis, Cell Line, Cell Survival, Chemokine CXCL12, Chickens, Clathrin Heavy Chains, Culture Media, Gene Expression Profiling, Gene Expression Regulation, Iron Deficiencies, Oligonucleotide Array Sequence Analysis, Precursor Cells, B-Lymphoid, Promoter Regions, Genetic, Receptors, CXCR4, Signal Transduction, Tetracycline, Transferrin

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PLoS One

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Public Library of Science (PLoS)
BBSRC (BB/D001242/1)
The work was supported by the following: Department of Biochemistry, University of Cambridge, BBSRC, and Marie Curie Fellowship (FRMW). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.