Requirement for antiapoptotic MCL-1 during early erythropoiesis.
Blood
; 137(14): 1945-1958, 2021 04 08.
Article
em En
| MEDLINE
| ID: mdl-33512417
ABSTRACT
Although BCL-xL is critical to the survival of mature erythrocytes, it is still unclear whether other antiapoptotic molecules mediate survival during earlier stages of erythropoiesis. Here, we demonstrate that erythroid-specific Mcl1 deletion results in embryonic lethality beyond embryonic day 13.5 as a result of severe anemia caused by a lack of mature red blood cells (RBCs). Mcl1-deleted embryos exhibit stunted growth, ischemic necrosis, and decreased RBCs in the blood. Furthermore, we demonstrate that MCL-1 is only required during early definitive erythropoiesis; during later stages, developing erythrocytes become MCL-1 independent and upregulate the expression of BCL-xL. Functionally, MCL-1 relies upon its ability to prevent apoptosis to promote erythroid development because codeletion of the proapoptotic effectors Bax and Bak can overcome the requirement for MCL-1 expression. Furthermore, ectopic expression of human BCL2 in erythroid progenitors can compensate for Mcl1 deletion, indicating redundancy between these 2 antiapoptotic family members. These data clearly demonstrate a requirement for MCL-1 in promoting survival of early erythroid progenitors.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Deleção de Genes
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Regulação da Expressão Gênica no Desenvolvimento
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Eritropoese
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Proteína de Sequência 1 de Leucemia de Células Mieloides
Limite:
Animals
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Humans
Idioma:
En
Revista:
Blood
Ano de publicação:
2021
Tipo de documento:
Article