Abstract
LATS (large tumour suppressor) is a family of conserved tumour suppressors identified in Drosophila and mammals. Here we show that human LATS1 binds to LIMK1 in vitro and in vivo and colocalizes with LIMK1 at the actomyosin contractile ring during cytokinesis. LATS1 inhibits both the phosphorylation of cofilin by LIMK1 and LIMK1-induced cytokinesis defects. Inactivation of LATS1 by antibody microinjection or RNA-mediated interference in cells, or gene knockout in mice, abrogates cytokinesis and increases the percentage of multinucleate cells. Our findings indicate that LATS1 is a novel cytoskeleton regulator that affects cytokinesis by regulating actin polymerization through negative modulation of LIMK1.
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Acknowledgements
We thank T. Pollard, L. Cooley, A. Pater, R. Pagliarini, L. Pedraza and members of the Xu laboratory for critical reading of the manuscript, suggestions and discussion; X. Fei and K. Sepanek for assistance; and O. Bernard, A. Minden and C. Dan for LIMK1 plasmids. This work was supported by a grant from the National Institutes of Health (CA69408) to T.X., who is a Howard Hughes Medical Institute Associate Investigator. Y.X. is a recipient of a postdoctoral fellowship from the Canadian Institute of Health Research (CIHR) and is an Anne Fuller Fellow.
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Yang, X., Yu, K., Hao, Y. et al. LATS1 tumour suppressor affects cytokinesis by inhibiting LIMK1. Nat Cell Biol 6, 609–617 (2004). https://doi.org/10.1038/ncb1140
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DOI: https://doi.org/10.1038/ncb1140
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