Swanhart Lisa M, Sanders Akeisha N, Duronio Robert J
Department of Biology, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
Dev Dyn. 2007 Sep;236(9):2567-77. doi: 10.1002/dvdy.21265.
G1 Cyclin/Cdk complexes phosphorylate and inactivate the pRb tumor suppressor by preventing its ability to bind and repress E2F transcription factors. Current molecular and biochemical evidence suggests that type 1 protein phosphatases (PP1) dephosphorylate and thereby activate pRb, but the functional significance of this has not been addressed in the context of animal development. Here, we use genetic analyses to determine the role of PP1 in the regulation of Rbf1 activity during Drosophila development. While Rbf1 is required for E2f1 inhibition and G1 arrest in the embryonic epidermis and for the periodic expression of E2f1 target genes during endocycle S phase in the embryonic midgut and larval salivary gland, PP1 is not. PP1 regulates periodic cyclin E protein accumulation in ovarian nurse cells independently of Rbf1, which is dispensable for endocycle regulation in this tissue. We conclude that PP1 is not a major regulator of the Rbf1/E2F1 pathway in Drosophila.
G1 细胞周期蛋白/细胞周期蛋白依赖性激酶复合物通过阻止 pRb 肿瘤抑制因子结合并抑制 E2F 转录因子的能力，使其磷酸化并失活。目前的分子和生化证据表明，1 型蛋白磷酸酶（PP1）使 pRb 去磷酸化从而激活 pRb，但在动物发育背景下，其功能意义尚未得到探讨。在这里，我们利用遗传学分析来确定 PP1 在果蝇发育过程中对 Rbf1 活性调控的作用。虽然 Rbf1 对于胚胎表皮中 E2f1 的抑制和 G1 期阻滞以及胚胎中肠和幼虫唾液腺内复制周期 S 期 E2f1 靶基因的周期性表达是必需的，但 PP1 并非如此。PP1 独立于 Rbf1 调节卵巢滋养细胞中周期性细胞周期蛋白 E 的积累，而 Rbf1 对于该组织内复制周期的调节是可有可无的。我们得出结论，PP1 不是果蝇中 Rbf1/E2F1 通路的主要调节因子。
