Verdugo-Sivianes Eva M, Carnero Amancio
Instituto de Biomedicina de Sevilla, IBIS, Hospital Universitario Virgen del Rocio, Consejo Superior de Investigaciones Científicas, Universidad de Sevilla, Avda. Manuel Siurot s/n, 41013 Seville, Spain.
CIBERONC, Instituto de Salud Carlos III, 28029 Madrid, Spain.
Cancers (Basel). 2021 May 6;13(9):2226. doi: 10.3390/cancers13092226.
Cell cycle progression is highly regulated by modulating the phosphorylation status of the retinoblastoma protein (pRB) and the other two members of the RB family, p107 and p130. This process is controlled by a balance in the action of kinases, such as the complexes formed by cyclin-dependent kinases (CDKs) and cyclins, and phosphatases, mainly the protein phosphatase 1 (PP1). However, while the phosphorylation of the RB family has been largely studied, its dephosphorylation is less known. Phosphatases are holoenzymes formed by a catalytic subunit and a regulatory protein with substrate specificity. Recently, the PP1-Spinophilin (SPN) holoenzyme has been described as the main phosphatase responsible for the dephosphorylation of RB proteins during the G0/G1 transition and at the end of G1. Moreover, SPN has been described as a tumor suppressor dependent on PP1 in lung and breast tumors, where it promotes tumorigenesis by increasing the cancer stem cell pool. Therefore, a connection between the cell cycle and stem cell biology has also been proposed via SPN/PP1/RB proteins.
细胞周期进程通过调节视网膜母细胞瘤蛋白（pRB）以及RB家族的其他两个成员p107和p130的磷酸化状态而受到高度调控。这一过程由激酶（如细胞周期蛋白依赖性激酶（CDK）和细胞周期蛋白形成的复合物）和磷酸酶（主要是蛋白磷酸酶1（PP1））作用的平衡所控制。然而，虽然对RB家族的磷酸化已有大量研究，但其去磷酸化情况却鲜为人知。磷酸酶是由催化亚基和具有底物特异性的调节蛋白形成的全酶。最近，PP1-亲嗜素（SPN）全酶被描述为在G0/G1转换期间及G1期末负责RB蛋白去磷酸化的主要磷酸酶。此外，SPN在肺癌和乳腺癌中被描述为一种依赖PP1的肿瘤抑制因子，它通过增加癌症干细胞池来促进肿瘤发生。因此，也有人提出通过SPN/PP1/RB蛋白在细胞周期与干细胞生物学之间建立联系。
