Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago, Chicago, IL, USA.
Cell Cycle. 2010 Mar 1;9(5):1016-20. doi: 10.4161/cc.9.5.10953. Epub 2010 Mar 15.
The retinoblastoma protein (pRB) negatively regulates cell proliferation by limiting the activity of the family of E2F transcription factors. In Drosophila, mutation of the DEAD-box helicase belle (bel) relieves an E2F/pRB induced G(1) cell cycle arrest; however, the mechanism of this rescue is unknown. Here, we show that the level of the cyclin-dependent kinase inhibitor Dacapo (Dap), homolog of mammalian p21/p27, is strongly reduced both in bel mutant cells in vivo and in tissue culture cells depleted of Bel by RNA interference. Interestingly, the loss of bel also partially alleviates an ectopically induced G(1) cell cycle arrest. Additionally, we show that Bel undergoes nucleocytoplasmic shuttling. Thus, inactivation of bel renders cells less sensitive to several anti-proliferative signals inducing G(1) arrest.
视网膜母细胞瘤蛋白（pRB）通过限制 E2F 转录因子家族的活性来负调控细胞增殖。在果蝇中，DEAD 盒解旋酶 belle（bel）的突变缓解了 E2F/pRB 诱导的 G1 细胞周期阻滞；然而，这种拯救的机制尚不清楚。在这里，我们表明，细胞周期蛋白依赖性激酶抑制剂 Dacapo（Dap）的水平在体内 bel 突变细胞和通过 RNA 干扰耗尽 Bel 的组织培养细胞中均强烈降低，Dap 是哺乳动物 p21/p27 的同源物。有趣的是，bel 的缺失也部分缓解了异位诱导的 G1 细胞周期阻滞。此外，我们还表明 Bel 经历核质穿梭。因此，bel 的失活使细胞对诱导 G1 阻滞的几种抗增殖信号的敏感性降低。
