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Sci. STKE, 9 January 2007
Vol. 2007, Issue 368, p. tw11
[DOI: 10.1126/stke.3682007tw11]

EDITORS' CHOICE

Apoptosis Saved from Proteolysis

Elizabeth M. Adler

Science's STKE, AAAS, Washington, DC 20005, USA

Terminal erythroid differentiation in response to erythropoietin depends on caspase-3 activation, whereas erythropoietin withdrawal leads to caspase-mediated proteolysis of the transcription factor GATA-1 and apoptosis. Ribeil et al. observed that activated caspase-3 colocalized in the nucleus with GATA-1 during erythroid differentiation and wondered how GATA-1 escaped proteolysis. They found that during differentiation, the molecular chaperone Hsp3 (which was expressed constitutively by differentiating human erythroblasts) colocalized in the nucleus with GATA-1, whereas Hsp70 disappeared from the nucleus during erythropoietin starvation. Hsp70 coimmunoprecipitated with GATA-1 from differentiated erythroblasts and protected GATA-1 from caspase-3-mediated cleavage in an in vitro proteolysis assay. Hsp70 knockdown with siRNA led to GATA-1 degradation in differentiating cells as well as to a decrease in the proportion of differentiating cells and an increase in the rate of cell death. Moreover, a caspase-resistant GATA-1 mutant protected hematopoietic cells from the effects on cell maturation and death of siRNA directed against Hsp70. Thus, the authors propose that erythropoietin protects differentiating erythroid cells from apoptosis by promoting nuclear localization of Hsp70, thereby preventing GATA-1 proteolysis.

J.-A. Ribeil, Y. Zermati, J. Vandekerckhove, S. Cathelin, J. Kersual, M. Dussiot, S. Coulon, I. C. Moura, A. Zeuner, T. Kirkegaard-Sørensen, B. Varet, E. Solary, C. Garrido, O. Hermine, Hsp70 regulates erythropoiesis by preventing caspase-3-mediated cleavage of GATA-1. Nature 445, 102-105 (2007). [PubMed]

Citation: E. M. Adler, Saved from Proteolysis. Sci. STKE 2007, tw11 (2007).


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