Disruption of the regulatory β subunit of protein kinase CK2 in mice leads to a cell-autonomous defect and early embryonic lethality
Disruption of the regulatory β subunit of protein kinase CK2 in mice leads to a cell-autonomous defect and early embryonic lethality
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DOI：
10.1128/mcb.23.3.908-915.2003
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发表时间：
2003-02-01
影响因子：
5.3
通讯作者：
Boldyreff, B
中科院分区：
文献类型：
--
作者：
Buchou, T;Vernet, M;Boldyreff, B
蛋白激酶CK2是一种普遍存在的蛋白激酶，与细胞的增殖和存活有关。它的调节亚基CK2beta在哺乳动物中由单一基因编码，被怀疑调节其他蛋白激酶。在这项工作中，我们证明了CK2β基因在小鼠体内的敲除会导致移植后的死亡。在胚胎6.5天(E6.5)，突变胚胎的大小减小。它们没有表现出凋亡的迹象，但确实显示出细胞增殖减少。突变胚胎在e7.5时被吸收。在体外，CK2β(-/-)桑椹胚的发育在囊胚期后停止。培育纯合子胚胎干细胞的尝试失败了。通过使用条件性基因敲除方法，我们发现缺乏CK2β对小鼠ES细胞和原代胚胎成纤维细胞是有害的。这与酵母细胞的情况形成了鲜明对比，酵母细胞可以在没有CK2β功能的情况下存活。因此，我们的研究表明，在哺乳动物中，CK2β对于细胞水平的生存是必不可少的，可能是因为它在进化过程中获得了新的功能。
Protein kinase CK2 is a ubiquitous protein kinase implicated in proliferation and cell survival. Its regulatory 0 subunit, CK2beta, which is encoded by a single gene in mammals, has been suspected of regulating other protein kinases. In this work, we show that knockout of the CK2beta gene in mice leads to postimplantation lethality. Mutant embryos were reduced in size at embryonic day 6.5 (E6.5). They did not exhibit signs of apoptosis but did show reduced cell proliferation. Mutant embryos were resorbed at E7.5. In vitro, CK2beta(-/-) morula development stopped after the blastocyst stage. Attempts to generate homozygous embryonic stem (ES) cells failed. By using a conditional knockout approach, we show that lack of CK2beta is deleterious for mouse ES cells and primary embryonic fibroblasts. This is in contrast to what occurs with yeast cells, which can survive without functional CK2beta. Thus, our study demonstrates that in mammals, CK2beta is essential for viability at the cellular level, possibly because it acquired new functions during evolution.