KHDC1B is a novel CPEB binding partner specifically expressed in mouse oocytes and early embryos.
KHDC1B is a novel CPEB binding partner specifically expressed in mouse oocytes and early embryos.
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DOI：
10.1091/mbc.e10-03-0255
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发表时间：
2010-09-15
影响因子：
3.3
通讯作者：
Molyneaux K
中科院分区：
文献类型：
--
作者：
Cai C;Tamai K;Molyneaux K
检测了一个新的KH结构域蛋白家族的两个成员的表达和活性。KHDC1A和1B在卵母细胞中高度表达。基于异位表达，KHDC1A调节细胞凋亡，而1B与细胞质多聚腺苷酸化机制相互作用。KHDC1B可能是卵母细胞成熟过程中的翻译抑制因子。减数分裂成熟和早期胚胎发育所需的mRNA储存在生长的卵母细胞中。这些转录本被抑制，直到荷尔蒙刺激触发排卵。翻译错误是某些人类不育症的基础，并与卵巢生殖细胞肿瘤有关。然而，目前还不清楚母源转录本是如何在哺乳动物中保持静止的。本研究描述了一种潜在的翻译调节因子KHDC1B。KHDC1B是真兽目哺乳动物特异性KH结构域蛋白小家族的成员。两个家族成员，KHDC1A和1B，在卵母细胞中高度表达。KHDC1A和1B与polyU琼脂糖结合，形成类似于其他KH结构域蛋白的寡聚体。通过在非洲爪蟾胚胎中的表达来测试这些蛋白的功能。KHDC1A引起细胞死亡，而KHDC1B引起裂解停滞。这种停滞表型通过小鼠翻译调节因子胞质多聚腺苷酸化结合蛋白1（mCPEB 1）的共表达而被拯救。免疫共沉淀和免疫共染色实验证实了KHDC1B和mCPEB 1之间的功能相互作用。最后，KHDC1B水平和结合伴侣显示出随细胞周期波动。KHDC1B通过与mCEPB 1的相互作用，可以调节卵母细胞成熟所需的mRNA靶标的翻译。
The expression and activities of two members of a novel KH domain protein family were tested. KHDC1A and 1B are highly expressed in oocytes. Based on ectopic expression, KHDC1A regulates apoptosis whereas 1B interacts with the cytoplasmic polyadenylation machinery. KHDC1B may serve as a translational repressor during oocyte maturation. mRNAs required for meiotic maturation and early embryonic development are stored in growing oocytes. These transcripts are translationally repressed until hormonal cues trigger ovulation. Errors in translation underlie some cases of human infertility and are associated with ovarian germ cell tumors. However, it remains unclear how maternal transcripts are kept quiescent in mammals. This study describes a potential translational regulator, KHDC1B. KHDC1B is a member of a small family of KH-domain containing proteins specific to eutherian mammals. Two family members, KHDC1A and 1B, are highly expressed in oocytes. KHDC1A and 1B bind polyU agarose and form oligomers like other KH-domain proteins. The functions of these proteins were tested by expression in Xenopus embryos. KHDC1A caused cell death, whereas KHDC1B caused cleavage arrest. This arrest phenotype was rescued by coexpression of the mouse translational regulator cytoplasmic polyadenylation binding protein 1 (mCPEB1). Coimmunoprecipitation and coimmunostaining experiments confirmed the functional interaction between KHDC1B and mCPEB1. Finally, KHDC1B levels and binding partners were shown to fluctuate with the cell cycle. KHDC1B, via its interaction with mCEPB1, may regulate translation of mRNA targets required for oocyte maturation.