Regulatory role of CK2 during the progression of cell cycle
Regulatory role of CK2 during the progression of cell cycle
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DOI：
10.1007/s11010-005-3111-3
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发表时间：
2005-06-01
影响因子：
4.3
通讯作者：
Homma, Y
中科院分区：
文献类型：
--
作者：
Homma, MK;Homma, Y
蛋白激酶酪蛋白激酶2 （CK2）是一种普遍存在的真核丝氨酸/苏氨酸蛋白激酶，在细胞周期进程中起重要作用。我们发现(1)CK2与肿瘤抑制蛋白——大肠腺瘤性息肉病（APC）相互作用，在G(2)/M中发生率最高；(2)APC的c端区域，在氨基酸残基2086-2394之间，具有最强的抑制CK2的活性。该片段在HEK293细胞或APC蛋白突变体截断的结直肠癌细胞中过表达，可下调细胞增殖率和软琼脂上的集落形成。这些结果表明，CK2和全长APC之间的复合物形成调节CK2活性，进而调节细胞周期进程，而结肠直肠癌中截断的APC无法调节细胞周期。在寻找CK2下游靶点的过程中，我们发现真核翻译起始因子5 （eIF5）在体内和体外都被CK2磷酸化，这表明CK2通过eIF5促进细胞生长的重要作用。
The protein kinase casein kinase 2 (CK2) is a ubiquitous eukaryotic serine/threonine protein kinase that plays an important role in cell cycle progression. We find that (1) CK2 interacts with a tumor suppressor protein, adenomatous polyposis coli (APC) that occurs at the highest level in G(2)/M, and (2) the C-terminal region of APC, between amino acid residues 2086-2394, has the strongest activity to suppress CK2. Over-expression of this fragment in HEK293 cells or colorectal carcinoma cells that have truncated mutant APC proteins down-regulates cell proliferation rates as well as colony formation on soft agar. These results indicate that the complex formation between CK2 and full-length APC regulates CK2 activity that, in turn, regulates cell cycle progression, whereas truncated APC in colorectal carcinomas are unable to regulate the cell cycle. In the process to look for the downstream target for CK2, we found that eukaryotic translation initiation factor 5 (eIF5) is phosphorylated by CK2 in vivo as well as in vitro These results suggest an important role of CK2 on promotion of cell growth through eIF5.