PKU-beta/TLK1 regulates myosin II activities, and is required for accurate equaled chromosome segregation.
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.
Department of Biochemistry, Kanazawa Medical University, Uchinada 920-0293, Japan. mithashi@kanazawa-med.ac.jp
Mitsumasa
M
Hashimoto
Tadashi
T
Matsui
Kuniyoshi
K
Iwabuchi
Takayasu
T
Date
D000782:Aneuploidy; D002453:Cell Cycle; D020090:Chromosome Segregation; D005786:Gene Expression Regulation; D006801:Humans; D018994:Myosin Light Chains / Q000378:metabolism; D024462:Myosin Type II / Q000378:metabolism*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*
D018994:Myosin Light Chains; D017346:Protein Serine-Threonine Kinases; C425323:TLK1 protein, human; D024462:Myosin Type II