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Blood, 1 June 2004, Vol. 103, No. 11, pp. 4310-4316.
Prepublished online as a Blood First Edition Paper on February 19, 2004; DOI 10.1182/blood-2003-09-3362.

Submitted September 30, 2003
Accepted February 8, 2004
Caspase-3 has a Non-Apoptotic Function in Erythroid Maturation
Graeme W Carlile, Deborah H Smith, and Martin Wiedmann*
Cell Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY, USA; Weill Graduate School of Medical Sciences of Cornell University, New York, NY, USA
Cell Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY, USA
* Corresponding author; email: m-wiedmann{at}ski.mskcc.org.
Caspase-3 plays a central role in apoptosis. It is also activated in normal erythropoiesis, with its activity peaking early during development (CFU-E stage). In the present study, we have reduced the expression and subsequent enzymatic activity of caspase-3 by transfection of small interfering RNA (siRNA) directed to caspase-3 in a differentiating human erythroid culture system. We find that siRNA treatment yields a 50% reduction in cells that undergo enucleation with no change in the fraction of cells that undergo apoptosis, measured throughout the culture. Furthermore, a substantial fraction of treated cells are unable to complete the transition from pronormoblasts to basophilic normoblasts. These results demonstrate that caspase-3 is required for efficient erythropoiesis in this model system.

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