Erythropoietin activates caspase-3 and downregulates CAD during erythroid differentiation in TF-1 cells - a protection mechanism against DNA fragmentation.
The involvement of caspase-3 and its failure in the induction of DNA fragmentation during erythropoiesis were investigated with TF-1 cells. During erythroid differentiation, caspase-3 activation and cleavage of caspase-3 substrates such as ICAD (inhibitor of caspase-activated DNase) were detected without concomitant phosphatidyl-serine (PS) externalization and DNA fragmentation. These observations are in contrast to our understanding that DNA is degraded by CAD (caspase-activated DNase) when ICAD is cleaved by caspase-3. Our study demonstrates that CAD is downregulated at the mRNA and protein level during the erythroid differentiation in TF-1 cells. This provides a mechanism for the first time how cells avoid DNA fragmentation with activated caspase-3.
Lui
Julian Chun-Kin
JC
Department of Biochemistry, The Chinese University of Hong Kong, Shatin, NT, Hong Kong, China.
Kong
Siu-Kai
SK
D051017:Apoptosis Regulatory Proteins; D053148:Caspase 3; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism*; D002454:Cell Differentiation; D002478:Cells, Cultured; D053938:DNA Fragmentation / Q000187:drug effects*; D003851:Deoxyribonucleases / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation / Q000235:genetics*; D004789:Enzyme Activation; D041905:Erythroid Cells / Q000166:cytology* / Q000201:enzymology; D004920:Erythropoiesis / Q000502:physiology; D004921:Erythropoietin / Q000494:pharmacology*; D015870:Gene Expression; D006801:Humans; D011065:Poly(ADP-ribose) Polymerases; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins
D051017:Apoptosis Regulatory Proteins; D061945:Caspase Inhibitors; D011506:Proteins; D012333:RNA, Messenger; D011994:Recombinant Proteins; C109664:caspase-activated DNase inhibitor; D004921:Erythropoietin; D011065:Poly(ADP-ribose) Polymerases; D003851:Deoxyribonucleases; C109663:caspase-activated deoxyribonuclease; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases