Human CLK2 links cell cycle progression, apoptosis, and telomere length regulation
Human CLK2 links cell cycle progression, apoptosis, and telomere length regulation
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DOI：
10.1074/jbc.m300286200
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发表时间：
2003-06-13
影响因子：
4.8
通讯作者：
Hekimi, S
中科院分区：
文献类型：
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作者：
Jiang, N;Bénard, CY;Hekimi, S
秀丽隐杆线虫（Caelophabditis elegans）的E12 - 2基因的突变影响生物体特征，如发育、行为、生殖和衰老，以及细胞特征，如细胞周期、凋亡、DNA复制检查点和端粒长度。CLK- 2编码一种新的蛋白质（CLK- 2），在每个已测序的真核生物基因组中具有独特的同源物。我们已经研究了人类同源的CLK- 2（hCLK 2），以确定它是否影响相同的细胞功能的CLK- 2。我们发现，过表达的hCLK 2减少细胞周期的长度和hCLK 2表达的抑制可逆地阻止细胞周期。然而，hCLK 2的过表达使细胞对氧化应激或DNA复制阻断引发的凋亡高度敏感，并逐渐增加端粒长度。受CLK- 2影响的细胞功能模式的进化保守性表明，hCLK 2在人类中的功能也可能影响与蠕虫相同的生物体特征，包括寿命。令人惊讶的是，我们发现hCLK 2存在于所有细胞区室中，并且作为膜结合以及可溶形式存在。
Mutations in the clk- 2 gene of the nematode Caenorhabditis elegans affect organismal features such as development, behavior, reproduction, and aging as well as cellular features such as the cell cycle, apoptosis, the DNA replication checkpoint, and telomere length. clk- 2 encodes a novel protein ( CLK- 2) with a unique homologue in each of the sequenced eukaryotic genomes. We have studied the human homologue of CLK- 2 ( hCLK2) to determine whether it affects the same set of cellular features as CLK- 2. We find that overexpression of hCLK2 decreases cell cycle length and that inhibition of hCLK2 expression arrests the cell cycle reversibly. Overexpression of hCLK2, however, renders the cell hypersensitive to apoptosis triggered by oxidative stress or DNA replication block and gradually increases telomere length. The evolutionary conservation of the pattern of cellular functions affected by CLK- 2 suggests that the function of hCLK2 in humans might also affect the same organismal features as in worms, including life span. Surprisingly, we find that hCLK2 is present in all cellular compartments and exists as a membrane- associated as well as a soluble form.