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LATS1 tumour suppressor affects cytokinesis by inhibiting LIMK1

Nature Cell Biology volume 6, pages 609–617 (2004)Cite this article

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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Figure 1: Interaction between LATS1 and LIMK1 in vivo.
Figure 2: Interaction between LATS1 and LIMK1 in vitro.
Figure 3: Localization of LATS1 and LIMK1 during the cell cycle.
Figure 4: Colocalization of LATS1 and F-actin during mitosis and cytokinesis in HeLa cells.
Figure 5: LATS1 inhibits LIMK1 kinase activity in vitro and in vivo.
Figure 6: Effects of LATS1 and LIMK1 on cytokinesis.
Figure 7: Time-lapse video microscopy analysis of the effect of LATS1, LIMK1 and cofilin on cytokinesis.

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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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Authors and Affiliations

  1. Howard Hughes Medical Institute, Yale University School of Medicine, Boyer Center for Molecular Medicine, 295 Congress Avenue, New Haven, 06536-0812, CT, USA

    Xiaolong Yang, Yawei Hao, Da-ming Li & Tian Xu

  2. Department of Genetics, Yale University School of Medicine, Boyer Center for Molecular Medicine, 295 Congress Avenue, New Haven, 06536-0812, CT, USA

    Xiaolong Yang, Da-ming Li, Rodney Stewart & Tian Xu

  3. Department of Medicine, Yale University School of Medicine, Boyer Center for Molecular Medicine, 295 Congress Avenue, New Haven, 06536-0812, CT, USA

    Kuanping Yu & Karl L. Insogna

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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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