PKU-β/TLK1 regulates myosin II activities, and is required for accurate equaled chromosome segregation
PKU-β/TLK1 regulates myosin II activities, and is required for accurate equaled chromosome segregation
复制标题
DOI：
10.1016/j.mrgentox.2008.09.001
复制
发表时间：
2008-11-17
影响因子：
1.9
通讯作者：
Date, Takayasu
中科院分区：
文献类型：
--
作者：
Hashimoto, Mitsumasa;Matsui, Tadashi;Date, Takayasu
Tousled-like kinase 1（或蛋白激酶普遍存在，PKU-beta/TLK 1）是一种丝氨酸/苏氨酸蛋白激酶，参与染色质重塑，DNA复制和有丝分裂。RNAi介导的PKU-β/TLK 1缺失的人类细胞显示非整倍性，这些细胞的免疫荧光分析显示子染色体的不均等分离。免疫印迹显示PKU-β/TLK 1缺失细胞中肌球蛋白II调节轻链（MRLC）上Ser 19/Thr 18的磷酸化水平显著降低，而总MRLC蛋白没有变化。为了证实有丝分裂畸变和MRLC功能障碍之间的关系，我们在PKU-β/TLK 1耗尽的细胞中表达野生型MRLC或DD-MRLC（模拟二磷酸化;用天冬氨酸取代Thr 18和Ser 19）。DD-MRLC的表达显着减少了染色体的不平等分离。我们的数据表明，人类PKU-β/TLK 1通过在有丝分裂期间磷酸化MRLC来调节肌球蛋白II动力学，在染色体完整性中起重要作用。(C)2008 Elsevier B. V.保留所有权利。
Tousled-like kinase 1 (or protein kinase ubiquitous, PKU-beta/TLK1) is a serine/threonine protein kinase that is implicated in chromatin remodeling, DNA replication and mitosis. RNAi-mediated PKU-beta/TLK1-depleted human cells showed aneuploidy, and immunofluorescence analysis of these cells revealed the unequal segregation of daughter chromosomes. Immunoblots indicated a substantial reduction in the phosphorylation level of Ser19/Thr18 on the myosin II regulatory light chain (MRLC) in PKU-beta/TLK1-depleted cells, with no change in total MRLC protein. To confirm the relationship between mitotic aberration and MRLC dysfunction, we expressed wild type MRLC or DD-MRLC (mimics diphosphorylation; substitution of both Thr18 and Ser19 with aspartate) in PKU-beta/TLK1-depleted cells. DD-MRLC expression dramatically reduced the unequal segregation of chromosomes. Our data suggest that human PKU-beta/TLK1 plays an important role in chromosome integrity via the regulation of myosin II dynamics by phosphorylating MRLC during mitosis. (C) 2008 Elsevier B.V. All rights reserved.