Inhibition of neddylation causes meiotic arrest in mouse oocyte.
Cell Cycle
; 18(11): 1254-1267, 2019 06.
Article
em En
| MEDLINE
| ID: mdl-31111756
ABSTRACT
Mammalian oocyte meiosis is a special form of cell division that provides haploid gametes for fertilization. Unlike in mitosis, post-translational modifications (PTMs) are more crucial during meiosis because of the absence of de novo mRNA transcription. As a classic PTM, protein neddylation is a biological process that mediates protein degradation by modifying cullin proteins and activating the Cullin-Ring E3 ligases. This process plays important roles in various biological processes such as autophagy and tumorigenesis. However, the function of neddylation in germ cells is unknown. In this study, we observed that the inhibition of neddylation by its specific inhibitor MLN4924 significantly arrests mouse oocyte at the stage of metaphase during meiosis. The arrested oocytes display impaired spindles with over-activation of spindle assembly checkpoint (SAC). Accordingly, we identified early mitosis inhibitor 1 (Emi1), a key inhibitor of anaphase-promoting complex/cyclosome (APC/CFzr1), as a substrate of neddylation-mediated protein degradation. Thus, our study uncovered an unknown role of neddylation in female germ cells and suggests that proper neddylation is essential for oocyte maturation.
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Base de dados:
MEDLINE
Assunto principal:
Oócitos
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Pirimidinas
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Processamento de Proteína Pós-Traducional
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Ciclopentanos
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Pontos de Checagem do Ciclo Celular
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Proteína NEDD8
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Meiose
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article