The tumor suppressor Lats2 is pivotal in Aurora A and Aurora B signaling during mitosis

Norikazu Yabuta; Satomi Mukai; Nobuhiro Okada; Yael Aylon; Hiroshi Nojima

doi:10.4161/cc.10.16.16873

The tumor suppressor Lats2 is pivotal in Aurora A and Aurora B signaling during mitosis

Norikazu Yabuta, Satomi Mukai, Nobuhiro Okada, Yael Aylon, Hiroshi Nojima

Research output: Contribution to journal › Article › peer-review

49 Citations (Scopus)

Abstract

Accurate coordination between chromosome segregation and cytokinesis by various mitotic kinases, such as Aurora, prevent tetraploidization and subsequent tumorigensis. The tumor suppressors Lats1 and Lats2 are serine/threonine kinases that localize to the centrosome and regulate cell cycle progression and apoptosis. In the present study, Aurora A was demonstrated to phosphorylate Lats2 on serine 380 (S380) during mitosis. Immunocytochemical observations revealed that the subcellular localization of Lats2 was distinct during the cell cycle and depended on which site was phosphorylated. Interestingly, the S380-phosphorylated Lats2 protein (pS380) colocalized at the central spindle with Aurora B. Physical interactions were observed between Aurora A, Lats2, Lats1 and Aurora B. The Lats1 kinase was shown to phosphorylate Aurora B. Cells expressing a nonphosphorylated mutant (S380A) of Lats2 caused chromosome missegregation and cytokinesis failure, similar to the cells with aberrantly expressed Aurora B. Together, the results suggest that the Aurora A-Lats1/2-Aurora B axis might be a novel pathway that regulates accurate mitotic progression by ensuring the proper mitotic localization of Lats2.

Original language	English
Pages (from-to)	2724-2736
Number of pages	13
Journal	Cell Cycle
Volume	10
Issue number	16
DOIs	https://doi.org/10.4161/cc.10.16.16873
Publication status	Published - Aug 15 2011
Externally published	Yes

Keywords

Aurora-A
Aurora-B
Lats1
Lats2
Phosphorylation

ASJC Scopus subject areas

Molecular Biology
Developmental Biology
Cell Biology

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@article{74ac2bc4411647b7974373970e98153d,

title = "The tumor suppressor Lats2 is pivotal in Aurora A and Aurora B signaling during mitosis",

abstract = "Accurate coordination between chromosome segregation and cytokinesis by various mitotic kinases, such as Aurora, prevent tetraploidization and subsequent tumorigensis. The tumor suppressors Lats1 and Lats2 are serine/threonine kinases that localize to the centrosome and regulate cell cycle progression and apoptosis. In the present study, Aurora A was demonstrated to phosphorylate Lats2 on serine 380 (S380) during mitosis. Immunocytochemical observations revealed that the subcellular localization of Lats2 was distinct during the cell cycle and depended on which site was phosphorylated. Interestingly, the S380-phosphorylated Lats2 protein (pS380) colocalized at the central spindle with Aurora B. Physical interactions were observed between Aurora A, Lats2, Lats1 and Aurora B. The Lats1 kinase was shown to phosphorylate Aurora B. Cells expressing a nonphosphorylated mutant (S380A) of Lats2 caused chromosome missegregation and cytokinesis failure, similar to the cells with aberrantly expressed Aurora B. Together, the results suggest that the Aurora A-Lats1/2-Aurora B axis might be a novel pathway that regulates accurate mitotic progression by ensuring the proper mitotic localization of Lats2.",

keywords = "Aurora-A, Aurora-B, Lats1, Lats2, Phosphorylation",

author = "Norikazu Yabuta and Satomi Mukai and Nobuhiro Okada and Yael Aylon and Hiroshi Nojima",

note = "Funding Information: We thank Dr. Moshe Oren (Weizmann Institute of Science, Israel) for providing materials and Drs. Patrick Hughes and Kathryn Kadash-Edmondson (Bioedit, LTD.,) for critically reading the manuscript. We also thank Dr. Shingo Toji, Dr. Katsuyuki Tamai (MBL Co., LTD., Nagano, Japan), Mr. Souichi Nishihara, Dr. Jun Sato, Ms. Kana Ao, Ms. Mayumi Sugimoto, Ms. Atsuko Kuroki, Ms. Azumi Fujimori and Mr. Toshiya Hosomi (Osaka University) for technical assistance. This work was supported in part by Innovation Plaza Osaka of the Japan Science and Technology Agency (JST), as well as by Grants-in-aid for Scientific Research (B to H.N.; C to N.Y.) from the Ministry of Education, Culture, Sports, Science and Technology of Japan.",

year = "2011",

month = aug,

day = "15",

doi = "10.4161/cc.10.16.16873",

language = "English",

volume = "10",

pages = "2724--2736",

journal = "Cell Cycle",

issn = "1538-4101",

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TY - JOUR

T1 - The tumor suppressor Lats2 is pivotal in Aurora A and Aurora B signaling during mitosis

AU - Yabuta, Norikazu

AU - Mukai, Satomi

AU - Okada, Nobuhiro

AU - Aylon, Yael

AU - Nojima, Hiroshi

N1 - Funding Information: We thank Dr. Moshe Oren (Weizmann Institute of Science, Israel) for providing materials and Drs. Patrick Hughes and Kathryn Kadash-Edmondson (Bioedit, LTD.,) for critically reading the manuscript. We also thank Dr. Shingo Toji, Dr. Katsuyuki Tamai (MBL Co., LTD., Nagano, Japan), Mr. Souichi Nishihara, Dr. Jun Sato, Ms. Kana Ao, Ms. Mayumi Sugimoto, Ms. Atsuko Kuroki, Ms. Azumi Fujimori and Mr. Toshiya Hosomi (Osaka University) for technical assistance. This work was supported in part by Innovation Plaza Osaka of the Japan Science and Technology Agency (JST), as well as by Grants-in-aid for Scientific Research (B to H.N.; C to N.Y.) from the Ministry of Education, Culture, Sports, Science and Technology of Japan.

PY - 2011/8/15

Y1 - 2011/8/15

N2 - Accurate coordination between chromosome segregation and cytokinesis by various mitotic kinases, such as Aurora, prevent tetraploidization and subsequent tumorigensis. The tumor suppressors Lats1 and Lats2 are serine/threonine kinases that localize to the centrosome and regulate cell cycle progression and apoptosis. In the present study, Aurora A was demonstrated to phosphorylate Lats2 on serine 380 (S380) during mitosis. Immunocytochemical observations revealed that the subcellular localization of Lats2 was distinct during the cell cycle and depended on which site was phosphorylated. Interestingly, the S380-phosphorylated Lats2 protein (pS380) colocalized at the central spindle with Aurora B. Physical interactions were observed between Aurora A, Lats2, Lats1 and Aurora B. The Lats1 kinase was shown to phosphorylate Aurora B. Cells expressing a nonphosphorylated mutant (S380A) of Lats2 caused chromosome missegregation and cytokinesis failure, similar to the cells with aberrantly expressed Aurora B. Together, the results suggest that the Aurora A-Lats1/2-Aurora B axis might be a novel pathway that regulates accurate mitotic progression by ensuring the proper mitotic localization of Lats2.

AB - Accurate coordination between chromosome segregation and cytokinesis by various mitotic kinases, such as Aurora, prevent tetraploidization and subsequent tumorigensis. The tumor suppressors Lats1 and Lats2 are serine/threonine kinases that localize to the centrosome and regulate cell cycle progression and apoptosis. In the present study, Aurora A was demonstrated to phosphorylate Lats2 on serine 380 (S380) during mitosis. Immunocytochemical observations revealed that the subcellular localization of Lats2 was distinct during the cell cycle and depended on which site was phosphorylated. Interestingly, the S380-phosphorylated Lats2 protein (pS380) colocalized at the central spindle with Aurora B. Physical interactions were observed between Aurora A, Lats2, Lats1 and Aurora B. The Lats1 kinase was shown to phosphorylate Aurora B. Cells expressing a nonphosphorylated mutant (S380A) of Lats2 caused chromosome missegregation and cytokinesis failure, similar to the cells with aberrantly expressed Aurora B. Together, the results suggest that the Aurora A-Lats1/2-Aurora B axis might be a novel pathway that regulates accurate mitotic progression by ensuring the proper mitotic localization of Lats2.

KW - Aurora-A

KW - Aurora-B

KW - Lats1

KW - Lats2

KW - Phosphorylation

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JO - Cell Cycle

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SN - 1538-4101

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