PKU-β/TLK1 regulates myosin II activities, and is required for accurate equaled chromosome segregation

被引:12
作者
Hashimoto, Mitsumasa [1 ]
Matsui, Tadashi [1 ]
Iwabuchi, Kuniyoshi [1 ]
Date, Takayasu [1 ]
机构
[1] Kanazawa Med Univ, Dept Biochem, Uchinada, Ishikawa 9200293, Japan
关键词
PKU-beta/TLK1; Myosin II; Chromosome segregation;
D O I
10.1016/j.mrgentox.2008.09.001
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
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.
引用
收藏
页码:63 / 67
页数:5
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