Caspase Activation Is Required for Terminal Erythroid Differentiation

Author:

Zermati Yael1,Garrido Carmen2,Amsellem Sophie3,Fishelson Serge3,Bouscary Didier4,Valensi Françoise5,Varet Bruno16,Solary Eric2,Hermine Olivier16

Affiliation:

1. Centre National de la Recherche Scientifique Unité Mixte de Recherche 8603, Université René Descartes (Paris V), Institut Fédérative de Recherche Necker, 75743 Paris cedex 15, France

2. Institut National de la Santé et de la Recherche Médicale (INSERM) U517, Unité Fédérative de Recherche Medecine et Pharmacie, Dijon 21033, France

3. Laboratoire de Recherche d'Hémobiologie, Hôpital Cochin, 75014 Paris, France

4. INSERM U363, Hôpital Cochin, 75014 Paris, France

5. Laboratoire d'Hématologie, Université René Descartes (Paris V), Institut Fédérative de Recherche Necker, 75743 Paris cedex 15, France

6. Service d'Hématologie Clinique, Université René Descartes (Paris V), Institut Fédérative de Recherche Necker, 75743 Paris cedex 15, France

Abstract

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.

Publisher

Rockefeller University Press

Subject

Immunology,Immunology and Allergy

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