Kim T Y, Kaelin W G
Brigham and Womens Hospital and Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
Mol Biol Cell. 2001 Jul;12(7):2207-17. doi: 10.1091/mbc.12.7.2207.
Different cyclins mediate different cell-cycle transitions. Some cyclins, such as cyclin A and cyclin E, form stable complexes with proteins that bind directly or indirectly to DNA and thus might be recruited to certain regions of the genome at specific times in the cell cycle. Furthermore, cyclins contain structural motifs that are also present in known transcriptional modulators. We found that cyclin A is a potent transcriptional repressor and cyclin E is a potent transcriptional activator when bound to DNA via a heterologous DNA binding domain. The former activity was linked to the integrity of the cyclin A cyclin fold, whereas the latter activity related to the ability of cyclin E to activate cdk2 and recognize substrates. Furthermore, we found that cyclin E, but not cyclin A, activated transcription in a cell-cycle-dependent manner when present in physiological concentrations as an unfused protein. These results suggest that cyclin A and cyclin E intrinsically differ with respect to their ability to modulate transcription when tethered to DNA.
不同的细胞周期蛋白介导不同的细胞周期转换。一些细胞周期蛋白，如细胞周期蛋白A和细胞周期蛋白E，与直接或间接结合DNA的蛋白质形成稳定复合物，因此可能在细胞周期的特定时间被招募到基因组的某些区域。此外，细胞周期蛋白含有已知转录调节因子中也存在的结构基序。我们发现，当通过异源DNA结合域与DNA结合时，细胞周期蛋白A是一种有效的转录抑制因子，而细胞周期蛋白E是一种有效的转录激活因子。前者的活性与细胞周期蛋白A的细胞周期蛋白折叠的完整性有关，而后者的活性与细胞周期蛋白E激活cdk2和识别底物的能力有关。此外，我们发现，当以未融合蛋白的形式存在于生理浓度时，细胞周期蛋白E而非细胞周期蛋白A以细胞周期依赖性方式激活转录。这些结果表明，当与DNA相连时，细胞周期蛋白A和细胞周期蛋白E在调节转录的能力上本质上是不同的。
