[Erythropoiesis: a paradigm for the role of caspases in cell death and differentiation].
Erythroid differentiation involves the transcription factor GATA-1 that positively regulates promoters of erythroid genes (including haemoglobin, glycophorin, erythropoietin receptor) and of erythropoietin. Terminal erythroid differentiation is characterized by major morphological changes that include chromatin condensation and cell size reduction. The morphological changes are partially similar at least to those observed during apoptosis. The production of red cells depends on the apoptosis rate of erythroid progenitors and precursors. Upon erythropoietin starvation or engagement of the death receptor Fas, caspases are activated in erythroid precursors and cleave GATA-1, thus inducing maturation arrest and apoptosis of immature erythroblasts. We have recently demonstrated that, upon erythropoietin stimulation, caspase-3 was also activated, an event required for human terminal erythroblast maturation. Proteins cleaved by caspases in erythroid cells undergoing terminal differentiation include Lamin B and Acinus, which are involved in chromatin condensation. In contrast, despite caspase-3 activation neither GATA-1 degradation nor apoptosis was observed. Thus, the fate of erythroid precursors is determined downstream of caspase activation by the pattern of cleaved targets. Therefore, there are some mechanisms underlying the selective protection of caspase-3 targets during erythropoiesis. This model in which caspases activation is required for differentiation may apply to other haematopoietic or non haematopoietic cellular systems which are described in this review.
CNRS UMR 8147 et Département d'Hématologie, Faculté de Médecine et Université René Descartes Paris V, Hôpital Necker, France, 75743 Cedex 15.
J A
JA
Ribeil
Y
Y
Zermati
J
J
Vandekerckhove
M
M
Dussiot
J
J
Kersual
O
O
Hermine
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001798:Blood Proteins / Q000378:metabolism; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology*; D004789:Enzyme Activation; D004900:Erythroblasts / Q000166:cytology / Q000201:enzymology; D004912:Erythrocytes / Q000166:cytology / Q000201:enzymology; D015672:Erythroid Precursor Cells / Q000166:cytology / Q000201:enzymology; D004920:Erythropoiesis / Q000502:physiology*; D050982:GATA1 Transcription Factor / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D007668:Kidney / Q000502:physiology; D008533:Megakaryocytes / Q000166:cytology / Q000201:enzymology; D008954:Models, Biological; D009687:Nuclear Proteins / Q000502:physiology; D019089:Stem Cell Factor / Q000502:physiology; D019014:fas Receptor / Q000502:physiology
D001798:Blood Proteins; D050982:GATA1 Transcription Factor; D009687:Nuclear Proteins; D019089:Stem Cell Factor; D019014:fas Receptor; C505407:CASP3 protein, human; C505530:CASP8 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases