Departamento de Inmunología y Oncología, Centro Nacional de Biotecnología-CSIC, Campus de Cantoblanco-UAM, Madrid, Spain.
Biochem Biophys Res Commun. 2010 Aug 13;399(1):84-90. doi: 10.1016/j.bbrc.2010.07.046. Epub 2010 Jul 17.
Human disc-large (hDlg) is a scaffold protein critical for the maintenance of cell polarity and adhesion. hDlg is thought to be a tumour suppressor that regulates the cell cycle and proliferation. However, the mechanism and pathways involved in hDlg regulation during these processes is still unclear. Here we report that hDlg is phosphorylated during mitosis, and we establish the identity of at least three residues phosphorylated in hDlg; some are previously unreported. Phosphorylation affects hDlg localisation excluding it from the contact point between the two daughter cells. Our results reveal a previously unreported pathway for hDlg phosphorylation in mitosis and show that ERK5 pathway mediates hDlg cell cycle dependent phosphorylation. This is likely to have important implications in the correct timely mitotic entry and mitosis progression.
人盘状结构域（hDlg）是一种对维持细胞极性和黏附至关重要的支架蛋白。hDlg 被认为是一种肿瘤抑制因子，可调节细胞周期和增殖。然而，在这些过程中 hDlg 调节的机制和途径尚不清楚。在这里，我们报告 hDlg 在有丝分裂期间发生磷酸化，并且我们确定了 hDlg 中至少三个被磷酸化的残基；其中一些以前未被报道。磷酸化会影响 hDlg 的定位，使其无法出现在两个子细胞之间的接触点上。我们的结果揭示了有丝分裂中 hDlg 磷酸化的一条以前未被报道的途径，并表明 ERK5 途径介导 hDlg 细胞周期依赖性磷酸化。这可能对正确的有丝分裂进入和有丝分裂进程具有重要意义。
