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14-3-3 epsilon prevents G2/M transition of fertilized mouse eggs by binding with CDC25B

BACKGROUND: The 14-3-3 (YWHA) proteins are highly conserved in higher eukaryotes, participate in various cellular signaling pathways including cell cycle regulation, development and growth. Our previous studies demonstrated that 14-3-3ε (YWHAE) is responsible for maintaining prophase | arrest in mou...

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Detalles Bibliográficos
Autores principales: Cui, Cheng, Ren, Xiuli, Liu, Dajun, Deng, Xin, Qin, Xin, Zhao, Xiangyu, Wang, Enhua, Yu, Bingzhi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222595/
https://www.ncbi.nlm.nih.gov/pubmed/25059436
http://dx.doi.org/10.1186/s12861-014-0033-x
Descripción
Sumario:BACKGROUND: The 14-3-3 (YWHA) proteins are highly conserved in higher eukaryotes, participate in various cellular signaling pathways including cell cycle regulation, development and growth. Our previous studies demonstrated that 14-3-3ε (YWHAE) is responsible for maintaining prophase | arrest in mouse oocyte. However, roles of 14-3-3ε in the mitosis of fertilized mouse eggs have remained unclear. Here, we showed that 14-3-3ε interacts and cooperates with CDC25B phosphorylated at Ser321 regulating G2/M transition of mitotic progress of fertilized mouse eggs. RESULTS: Disruption of 14-3-3ε expression by RNAi prevented normal G2/M transition by inhibition of MPF activity and leaded to the translocation of CDC25B into the nucleus from the cytoplasm. Overexpression of 14-3-3ε-WT and unphosphorylatable CDC25B mutant (CDC25B-S321A) induced mitotic resumption in dbcAMP-arrested eggs. In addition, we examined endogenous and exogenous distribution of 14-3-3ε and CDC25B. Endogenous 14-3-3ε and CDC25B were co-localized primarily in the cytoplasm at the G1, S, early G2 and M phases whereas CDC25B was found to accumulate in the nucleus at the late G2 phase. Upon coexpression with RFP–14-3-3ε, GFP–CDC25B–WT and GFP–CDC25B–S321A were predominantly cytoplasmic at early G2 phase and then GFP–CDC25B–S321A moved to the nucleus whereas CDC25B-WT signals were observed in the cytoplasm without nucleus accumulation at late G2 phase at presence of dbcAMP. CONCLUSIONS: Our data indicate that 14-3-3ε is required for the mitotic entry in the fertilized mouse eggs. 14-3-3ε is primarily responsible for sequestering the CDC25B in cytoplasm and 14-3-3ε binding to CDC25B-S321 phosphorylated by PKA induces mitotic arrest at one-cell stage by inactivation of MPF in fertilized mouse eggs.