LATS1/WARTS phosphorylates MYPT1 to counteract PLK1 and regulate mammalian mitotic progression

Tatsuyuki Chiyoda, Naoyuki Sugiyama, Takatsune Shimizu, Hideaki Naoe, Yusuke Kobayashi, Jo Ishizawa, Yoshimi Arima, Hiroshi Tsuda, Masaaki Ito, Kozo Kaibuchi, Daisuke Aoki, Yasushi Ishihama, Hideyuki Saya, Shinji Kuninaka

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Abstract

In the mitotic exit network of budding yeast, Dbf2 kinase phosphorylates and regulates Cdc14 phosphatase. In contrast, no phosphatase substrates of LATS1/WARTS kinase, the mammalian equivalent of Dbf2, has been reported. To address this discrepancy, we performed phosphoproteomic screening using LATS1 kinase. Screening identified MYPT1 (myosin phosphatase- targeting subunit 1) as a new substrate for LATS1. LATS1 directly and preferentially phosphorylated serine 445 (S445) of MYPT1. An MYPT1 mutant (S445A) failed to dephosphorylate Thr 210 of PLK1 (pololike kinase 1), thereby activating PLK1. This suggests that LATS1 promotes MYPT1 to antagonize PLK1 activity. Consistent with this, LATS1-depleted HeLa cells or fibroblasts from LATS1 knockout mice showed increased PLK1 activity. We also found deoxyribonucleic acid (DNA) damage-induced LATS1 activation caused PLK1 suppression via the phosphorylation of MYPT1 S445. Furthermore, LATS1 knockdown cells showed reduced G2 checkpoint arrest after DNA damage. These results indicate that LATS1 phosphorylates a phosphatase as does the yeast Dbf2 and demonstrate a novel role of LATS1 in controlling PLK1 at the G2 DNA damage checkpoint.

Original languageEnglish
Pages (from-to)625-641
Number of pages17
JournalJournal of Cell Biology
Volume197
Issue number5
DOIs
Publication statusPublished - 2012 May

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Myosin-Light-Chain Phosphatase
Phosphotransferases
Phosphoric Monoester Hydrolases
Serine
DNA
Saccharomycetales
HeLa Cells
Knockout Mice
Fibroblasts
Yeasts
Phosphorylation

ASJC Scopus subject areas

  • Cell Biology

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LATS1/WARTS phosphorylates MYPT1 to counteract PLK1 and regulate mammalian mitotic progression. / Chiyoda, Tatsuyuki; Sugiyama, Naoyuki; Shimizu, Takatsune; Naoe, Hideaki; Kobayashi, Yusuke; Ishizawa, Jo; Arima, Yoshimi; Tsuda, Hiroshi; Ito, Masaaki; Kaibuchi, Kozo; Aoki, Daisuke; Ishihama, Yasushi; Saya, Hideyuki; Kuninaka, Shinji.

In: Journal of Cell Biology, Vol. 197, No. 5, 05.2012, p. 625-641.

Research output: Contribution to journalArticle

Chiyoda, T, Sugiyama, N, Shimizu, T, Naoe, H, Kobayashi, Y, Ishizawa, J, Arima, Y, Tsuda, H, Ito, M, Kaibuchi, K, Aoki, D, Ishihama, Y, Saya, H & Kuninaka, S 2012, 'LATS1/WARTS phosphorylates MYPT1 to counteract PLK1 and regulate mammalian mitotic progression', Journal of Cell Biology, vol. 197, no. 5, pp. 625-641. https://doi.org/10.1083/jcb.201110110
Chiyoda, Tatsuyuki ; Sugiyama, Naoyuki ; Shimizu, Takatsune ; Naoe, Hideaki ; Kobayashi, Yusuke ; Ishizawa, Jo ; Arima, Yoshimi ; Tsuda, Hiroshi ; Ito, Masaaki ; Kaibuchi, Kozo ; Aoki, Daisuke ; Ishihama, Yasushi ; Saya, Hideyuki ; Kuninaka, Shinji. / LATS1/WARTS phosphorylates MYPT1 to counteract PLK1 and regulate mammalian mitotic progression. In: Journal of Cell Biology. 2012 ; Vol. 197, No. 5. pp. 625-641.
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