Caspase activation is required for terminal erythroid differentiation.
The cysteine proteases known as caspases play a central role in most apoptotic pathways. Here, we show that caspase inhibitors arrest the maturation of human erythroid progenitors at early stages of differentiation, before nucleus and chromatin condensation. Effector caspases such as caspase-3 are transiently activated through the mitochondrial pathway during erythroblast differentiation and cleave proteins involved in nucleus integrity (lamin B) and chromatin condensation (acinus)without inducing cell death and cleavage of GATA-1. These observations indicate a new function for caspases as key proteases in the process of erythroid differentiation.
Zermati
Y
Y
Centre National de la Recherche Scientifique Unité Mixte de Recherche 8603, Université René Descartes, Paris V, France.
Garrido
C
C
Amsellem
S
S
Fishelson
S
S
Bouscary
D
D
Valensi
F
F
Varet
B
B
Solary
E
E
Hermine
O
O
D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D004789:Enzyme Activation; D004900:Erythroblasts / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D004912:Erythrocytes / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D004920:Erythropoiesis / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects
D000590:Amino Acid Chloromethyl Ketones; D061945:Caspase Inhibitors; D015853:Cysteine Proteinase Inhibitors; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; D020169:Caspases