Zyxin, a Regulator of Actin Filament Assembly, Targets the Mitotic Apparatus by Interacting with H-warts/LATS1 Tumor Suppressor

Overview

Journal J Cell Biol

Specialty Cell Biology

Date 2000 Jun 1

PMID 10831611

Citations 94

Authors

T Hirota

T Morisaki

Y Nishiyama

T Marumoto

K Tada

T Hara

N MASUKO

M Inagaki

K Hatakeyama

H Saya

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

Deciphering the Role of BCAR3 in Cancer Progression: Gene Regulation, Signal Transduction, and Therapeutic Implications.

Moon D Cancers (Basel). 2024; 16(9).

PMID: 38730626 PMC: 11083344. DOI: 10.3390/cancers16091674.

The ability of the LIMD1 and TRIP6 LIM domains to bind strained f-actin is critical for their tension dependent localization to adherens junctions and association with the Hippo pathway kinase LATS1.

Ray S, DeSilva C, Dasgupta I, Mana-Capelli S, Cruz-Calderon N, McCollum D Cytoskeleton (Hoboken). 2024; 81(9-10):436-447.

PMID: 38426816 PMC: 11366040. DOI: 10.1002/cm.21847.

Zyxin Inhibits the Proliferation, Migration, and Invasion of Osteosarcoma via Rap1-Mediated Inhibition of the MEK/ERK Signaling Pathway.

Wei Z, Xia K, Zhou B, Zheng D, Guo W Biomedicines. 2023; 11(8).

PMID: 37626810 PMC: 10452081. DOI: 10.3390/biomedicines11082314.

Cell Cycle Regulation by Integrin-Mediated Adhesion.

Kamranvar S, Rani B, Johansson S Cells. 2022; 11(16).

PMID: 36010598 PMC: 9406542. DOI: 10.3390/cells11162521.

Molecular Alterations in Malignant Pleural Mesothelioma: A Hope for Effective Treatment by Targeting YAP.

Dubois F, Bazille C, Levallet J, Maille E, Brosseau S, Madelaine J Target Oncol. 2022; 17(4):407-431.

PMID: 35906513 PMC: 9345804. DOI: 10.1007/s11523-022-00900-2.

References

Justice R, Zilian O, Woods D, Noll M, Bryant P . The Drosophila tumor suppressor gene warts encodes a homolog of human myotonic dystrophy kinase and is required for the control of cell shape and proliferation. Genes Dev. 1995; 9(5):534-46. DOI: 10.1101/gad.9.5.534. View

Nishiyama Y, Hirota T, Morisaki T, Hara T, Marumoto T, Iida S . A human homolog of Drosophila warts tumor suppressor, h-warts, localized to mitotic apparatus and specifically phosphorylated during mitosis. FEBS Lett. 1999; 459(2):159-65. DOI: 10.1016/s0014-5793(99)01224-7. View

Williams B, Riedy M, Williams E, Gatti M, Goldberg M . The Drosophila kinesin-like protein KLP3A is a midbody component required for central spindle assembly and initiation of cytokinesis. J Cell Biol. 1995; 129(3):709-23. PMC: 2120429. DOI: 10.1083/jcb.129.3.709. View

Xu T, Wang W, Zhang S, Stewart R, Yu W . Identifying tumor suppressors in genetic mosaics: the Drosophila lats gene encodes a putative protein kinase. Development. 1995; 121(4):1053-63. DOI: 10.1242/dev.121.4.1053. View

Golsteyn R, Mundt K, Fry A, Nigg E . Cell cycle regulation of the activity and subcellular localization of Plk1, a human protein kinase implicated in mitotic spindle function. J Cell Biol. 1995; 129(6):1617-28. PMC: 2291169. DOI: 10.1083/jcb.129.6.1617. View

Reinhard M, Jouvenal K, Tripier D, Walter U . Identification, purification, and characterization of a zyxin-related protein that binds the focal adhesion and microfilament protein VASP (vasodilator-stimulated phosphoprotein). Proc Natl Acad Sci U S A. 1995; 92(17):7956-60. PMC: 41265. DOI: 10.1073/pnas.92.17.7956. View

IZAWA I, Tamaki N, Saya H . Phosphorylation of neurofibromatosis type 1 gene product (neurofibromin) by cAMP-dependent protein kinase. FEBS Lett. 1996; 382(1-2):53-9. DOI: 10.1016/0014-5793(96)00137-8. View

Hobert O, Schilling J, Beckerle M, Ullrich A, Jallal B . SH3 domain-dependent interaction of the proto-oncogene product Vav with the focal contact protein zyxin. Oncogene. 1996; 12(7):1577-81. View

Craig S, Johnson R . Assembly of focal adhesions: progress, paradigms, and portents. Curr Opin Cell Biol. 1996; 8(1):74-85. DOI: 10.1016/s0955-0674(96)80051-2. View

10.

Macalma T, Otte J, Hensler M, Bockholt S, Louis H, Kalff-Suske M . Molecular characterization of human zyxin. J Biol Chem. 1996; 271(49):31470-8. DOI: 10.1074/jbc.271.49.31470. View

11.

Nigg E, Blangy A, Lane H . Dynamic changes in nuclear architecture during mitosis: on the role of protein phosphorylation in spindle assembly and chromosome segregation. Exp Cell Res. 1996; 229(2):174-80. DOI: 10.1006/excr.1996.0356. View

12.

Kimura M, Kotani S, Hattori T, Sumi N, Yoshioka T, Todokoro K . Cell cycle-dependent expression and spindle pole localization of a novel human protein kinase, Aik, related to Aurora of Drosophila and yeast Ipl1. J Biol Chem. 1997; 272(21):13766-71. DOI: 10.1074/jbc.272.21.13766. View

13.

Nix D, Beckerle M . Nuclear-cytoplasmic shuttling of the focal contact protein, zyxin: a potential mechanism for communication between sites of cell adhesion and the nucleus. J Cell Biol. 1997; 138(5):1139-47. PMC: 2136768. DOI: 10.1083/jcb.138.5.1139. View

14.

Yamaguchi R, Mazaki Y, Hirota K, Hashimoto S, Sabe H . Mitosis specific serine phosphorylation and downregulation of one of the focal adhesion protein, paxillin. Oncogene. 1997; 15(15):1753-61. DOI: 10.1038/sj.onc.1201345. View

15.

Beckerle M . Zyxin: zinc fingers at sites of cell adhesion. Bioessays. 1997; 19(11):949-57. DOI: 10.1002/bies.950191104. View

16.

Terada Y, Tatsuka M, Suzuki F, Yasuda Y, Fujita S, Otsu M . AIM-1: a mammalian midbody-associated protein required for cytokinesis. EMBO J. 1998; 17(3):667-76. PMC: 1170416. DOI: 10.1093/emboj/17.3.667. View

17.

Giansanti M, Bonaccorsi S, Williams B, Williams E, Santolamazza C, Goldberg M . Cooperative interactions between the central spindle and the contractile ring during Drosophila cytokinesis. Genes Dev. 1998; 12(3):396-410. PMC: 316479. DOI: 10.1101/gad.12.3.396. View

18.

Nurse P . A long twentieth century of the cell cycle and beyond. Cell. 2000; 100(1):71-8. DOI: 10.1016/s0092-8674(00)81684-0. View

19.

Sunkel C, Glover D . polo, a mitotic mutant of Drosophila displaying abnormal spindle poles. J Cell Sci. 1988; 89 ( Pt 1):25-38. DOI: 10.1242/jcs.89.1.25. View

20.

Bailly E, Doree M, Nurse P, Bornens M . p34cdc2 is located in both nucleus and cytoplasm; part is centrosomally associated at G2/M and enters vesicles at anaphase. EMBO J. 1989; 8(13):3985-95. PMC: 401573. DOI: 10.1002/j.1460-2075.1989.tb08581.x. View