Yale University School of Medicine, New Haven, CT 06520, USA.
Dev Biol. 2010 Aug 15;344(2):1011-25. doi: 10.1016/j.ydbio.2010.06.022. Epub 2010 Jun 23.
Proliferating germ cells in Caenorhabditiselegans provide a useful model system for deciphering fundamental mechanisms underlying the balance between proliferation and differentiation. Using gene expression profiling, we identified approximately 200 genes upregulated in the proliferating germ cells of C. elegans. Functional characterization using RNA-mediated interference demonstrated that over forty of these factors are required for normal germline proliferation and development. Detailed analysis of two of these factors defined an important regulatory relationship controlling germ cell proliferation. We established that the kinase VRK-1 is required for normal germ cell proliferation, and that it acts in part to regulate CEP-1(p53) activity. Loss of cep-1 significantly rescued the proliferation defects of vrk-1 mutants. We suggest that VRK-1 prevents CEP-1 from triggering an inappropriate cell cycle arrest, thereby promoting germ cell proliferation. This finding reveals a previously unsuspected mechanism for negative regulation of p53 activity in germ cells to control proliferation.
秀丽隐杆线虫中增殖的生殖细胞为解析增殖和分化之间平衡的基本机制提供了一个有用的模型系统。我们通过基因表达谱分析，鉴定出大约 200 个在 C. elegans 增殖的生殖细胞中上调的基因。使用 RNA 介导的干扰进行功能表征表明，其中四十多个因素对于正常的生殖系增殖和发育是必需的。对其中两个因素的详细分析定义了控制生殖细胞增殖的一个重要调节关系。我们确定激酶 VRK-1 是正常生殖细胞增殖所必需的，并且它部分起作用来调节 CEP-1(p53)活性。cep-1 的缺失显著挽救了 vrk-1 突变体的增殖缺陷。我们认为 VRK-1 防止 CEP-1 引发不适当的细胞周期停滞，从而促进生殖细胞增殖。这一发现揭示了一种以前未被察觉的机制，用于负调控生殖细胞中 p53 活性以控制增殖。
