Caspase-3 Regulates YAP-Dependent Cell Proliferation and Organ Size.
Mol Cell
; 70(4): 573-587.e4, 2018 05 17.
Article
em En
| MEDLINE
| ID: mdl-29775577
ABSTRACT
Apoptosis culminates in the activation of caspase-3, which plays an important role in implementing the cell death program. Here, we reveal a non-apoptotic role of caspase-3 as a key regulator of cell proliferation and organ size. Caspase-3 is specifically activated in the proliferating cells of the sebaceous gland, but does not instruct cell elimination. Deletion or chemical inhibition of caspase-3 diminishes cell proliferation, decreases cell number and reduces sebaceous gland size in vivo. Exploring the underlying mechanism, we demonstrate that α-catenin is cleaved by caspase-3, thus facilitating the activation and nuclear translocation of yes-associated protein (YAP), a vital regulator of organ size. Accordingly, activation of caspase-3 leads to YAP-dependent organ size augmentation. Finally, we show that X-linked inhibitor of apoptosis protein (XIAP) serves as an endogenous feedback antagonist for the caspase-3/YAP signaling module. Taken together, we report here a molecular mechanism wherein the apoptotic machinery is refocused to regulate cell proliferation and orchestrate organ size.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fosfoproteínas
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Retroalimentação Fisiológica
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Proteínas Adaptadoras de Transdução de Sinal
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Proliferação de Células
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Proteínas Inibidoras de Apoptose
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Alfa Catenina
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Caspase 3
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Fatores de Processamento de RNA
Limite:
Animals
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article