School of Life Science, Lanzhou University, Lanzhou, Gans, China.
Lanzhou University Second Hospital, Lanzhou, Gansu, China.
Acta Biochim Biophys Sin (Shanghai). 2019 Mar 1;51(3):313-322. doi: 10.1093/abbs/gmy174.
Activation of transcription factor STAT3 is involved in cell proliferation, differentiation, and cell survival. Constitutive activation of STAT3 pathway has been associated with the oncogenesis of various types of cancers. It has been reported that STAT3 plays a key role in the G1 to S phase cell cycle transition induced by the cytokine receptor subunit gp130, through the upregulation of cyclins D1, D2, D3, A, and Cdc25A and the concomitant downregulation of p21 and p27. However, its role in mediating G2-M phase transition has not been studied. The cyclin B1/Cdc2 complex is widely accepted as the trigger of mitosis in all organisms and is believed to be necessary for progression through S phase and keep active during the G2-M transition and progression. In the present study, we found that activation of STAT3 stimulates cyclin B1 and Cdc2 expressions. Deletion and site-directed mutations on cyclin B1 and Cdc2 promoters indicated that E2F element mediates the upregulation of these two promoters in a STAT3-dependent manner. The findings reported here demonstrated that STAT3 participates in modulating G2-M phase checkpoint by regulating gene expressions of cyclin B1 and Cdc2 via E2F.
转录因子 STAT3 的激活涉及细胞增殖、分化和细胞存活。STAT3 通路的组成性激活与各种类型癌症的癌变有关。据报道，STAT3 通过上调细胞周期蛋白 D1、D2、D3、A 和 Cdc25A，同时下调 p21 和 p27，在由细胞因子受体亚基 gp130 诱导的 G1 到 S 期细胞周期转换中发挥关键作用。然而，其在介导 G2-M 期转换中的作用尚未得到研究。细胞周期蛋白 B1/Cdc2 复合物被广泛认为是所有生物体有丝分裂的触发因素，并且被认为是通过 S 期所必需的，并在 G2-M 转换和进展过程中保持活跃。在本研究中，我们发现 STAT3 的激活刺激了细胞周期蛋白 B1 和 Cdc2 的表达。细胞周期蛋白 B1 和 Cdc2 启动子的缺失和定点突变表明，E2F 元件以 STAT3 依赖的方式介导这两个启动子的上调。这里报道的研究结果表明，STAT3 通过 E2F 调节细胞周期蛋白 B1 和 Cdc2 的基因表达，参与调节 G2-M 期检查点。
