Zyxin, a regulator of actin filament assembly, targets the mitotic apparatus by interacting with h-warts/LATS1 tumor suppressor.
The mitotic apparatus plays a pivotal role in dividing cells to ensure each daughter cell receives a full set of chromosomes and complement of cytoplasm during mitosis. A human homologue of the Drosophila warts tumor suppressor, h-warts/LATS1, is an evolutionarily conserved serine/threonine kinase and a dynamic component of the mitotic apparatus. We have identified an interaction of h-warts/LATS1 with zyxin, a regulator of actin filament assembly. Zyxin is a component of focal adhesion, however, during mitosis a fraction of cytoplasmic-dispersed zyxin becomes associated with h-warts/LATS1 on the mitotic apparatus. We found that zyxin is phosphorylated specifically during mitosis, most likely by Cdc2 kinase, and that the phosphorylation regulates association with h-warts/LATS1. Furthermore, microinjection of truncated h-warts/LATS1 protein, including the zyxin-binding portion, interfered with localization of zyxin to mitotic apparatus, and the duration of mitosis of these injected cells was significantly longer than that of control cells. These findings suggest that h-warts/LATS1 and zyxin play a crucial role in controlling mitosis progression by forming a regulatory complex on mitotic apparatus.
Hirota
T
T
Department of Tumor Genetics and Biology, Kumamoto University School of Medicine, 2-2-1 Honjo, Kumamoto 860-0811, Japan.
Morisaki
T
T
Nishiyama
Y
Y
Marumoto
T
T
Tada
K
K
Hara
T
T
Masuko
N
N
Inagaki
M
M
Hatakeyama
K
K
Saya
H
H
D000199:Actins / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D000918:Antibody Specificity; D016203:CDC2 Protein Kinase / Q000378:metabolism; D019556:COS Cells / Q000166:cytology / Q000378:metabolism; D003598:Cytoskeletal Proteins; D029721:Drosophila Proteins; D015870:Gene Expression / Q000502:physiology; D016147:Genes, Tumor Suppressor / Q000502:physiology; D006023:Glycoproteins; D006367:HeLa Cells; D006801:Humans; D008667:Metalloproteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008938:Mitosis / Q000502:physiology; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology; D010766:Phosphorylation; D010957:Plasmids; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008941:Spindle Apparatus / Q000378:metabolism*; D016335:Zinc Fingers / Q000235:genetics; D060589:Zyxin
D000199:Actins; D003598:Cytoskeletal Proteins; D029721:Drosophila Proteins; D006023:Glycoproteins; D008667:Metalloproteins; D010446:Peptide Fragments; C092842:ZYX protein, human; D060589:Zyxin; D011494:Protein Kinases; C092745:LATS1 protein, human; C093503:wts protein, Drosophila; D017346:Protein Serine-Threonine Kinases; D016203:CDC2 Protein Kinase