Department of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala University, 751 85 Uppsala, Sweden.
BMC Mol Biol. 2011 Jul 7;12:28. doi: 10.1186/1471-2199-12-28.
CGGBP1 is a CGG-triplet repeat binding protein, which affects transcription from CGG-triplet-rich promoters such as the FMR1 gene and the ribosomal RNA gene clusters. Earlier, we reported some previously unknown functions of CGGBP1 in gene expression during heat shock stress response. Recently we had found CGGBP1 to be a cell cycle regulatory midbody protein required for normal cytokinetic abscission in normal human fibroblasts, which have all the cell cycle regulatory mechanisms intact.
In this study we explored the role of CGGBP1 in the cell cycle in various cancer cell lines. CGGBP1 depletion by RNA interference in tumor-derived cells caused an increase in the cell population at G0/G1 phase and reduced the number of cells in the S phase. CGGBP1 depletion also increased the expression of cell cycle regulatory genes CDKN1A and GAS1, associated with reductions in histone H3 lysine 9 trimethylation in their promoters. By combining RNA interference and genetic mutations, we found that the role of CGGBP1 in cell cycle involves multiple mechanisms, as single deficiencies of CDKN1A, GAS1 as well as TP53, INK4A or ARF failed to rescue the G0/G1 arrest caused by CGGBP1 depletion.
Our results show that CGGBP1 expression is important for cell cycle progression through multiple parallel mechanisms including the regulation of CDKN1A and GAS1 levels.
CGGBP1 是一个 CGG-三核苷酸重复结合蛋白，它影响 CGG-三核苷酸丰富启动子的转录，如 FMR1 基因和核糖体 RNA 基因簇。早些时候，我们报道了 CGGBP1 在热休克应激反应过程中基因表达方面的一些先前未知的功能。最近，我们发现 CGGBP1 是一种细胞周期调节的中体蛋白，对于正常人类成纤维细胞的正常胞质分裂分离是必需的，而正常人类成纤维细胞具有完整的细胞周期调节机制。
在这项研究中，我们探讨了 CGGBP1 在各种癌细胞系中的细胞周期中的作用。在肿瘤衍生细胞中通过 RNA 干扰使 CGGBP1 耗竭会导致 G0/G1 期细胞群体增加，而 S 期细胞数量减少。CGGBP1 耗竭还会增加细胞周期调节基因 CDKN1A 和 GAS1 的表达，与它们启动子中组蛋白 H3 赖氨酸 9 三甲基化的减少有关。通过 RNA 干扰和遗传突变的结合，我们发现 CGGBP1 在细胞周期中的作用涉及多种机制，因为 CDKN1A、GAS1 以及 TP53、INK4A 或 ARF 的单一缺陷都不能挽救 CGGBP1 耗竭引起的 G0/G1 期阻滞。
我们的结果表明，CGGBP1 的表达对于通过多个平行机制的细胞周期进展很重要，包括 CDKN1A 和 GAS1 水平的调节。
