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Hippo Signaling in Mitosis: An Updated View in Light of the MEN Pathway

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The Mitotic Exit Network

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1505))

Abstract

The Hippo pathway is an essential tumor suppressor signaling network that coordinates cell proliferation, death, and differentiation in higher eukaryotes. Intriguingly, the core components of the Hippo pathway are conserved from yeast to man, with the yeast analogs of mammalian MST1/2 (fly Hippo), MOB1 (fly Mats), LATS1/2 (fly Warts), and NDR1/2 (fly Tricornered) functioning as essential components of the mitotic exit network (MEN). Here, we update our previous summary of mitotic functions of Hippo core components in Drosophila melanogaster and mammals, with particular emphasis on similarities between the yeast MEN pathway and mitotic Hippo signaling. Mitotic functions of YAP and TAZ, the two main effectors of Hippo signaling, are also discussed.

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References

  1. Bardin AJ, Amon A (2001) Men and sin: what’s the difference? Nat Rev Mol Cell Biol 2(11):815–826. doi:10.1038/35099020

    Article  CAS  PubMed  Google Scholar 

  2. Hotz M, Barral Y (2014) The mitotic exit network: new turns on old pathways. Trends Cell Biol 24(3):145–152. doi:10.1016/j.tcb.2013.09.010

    Article  CAS  PubMed  Google Scholar 

  3. McCollum D, Gould KL (2001) Timing is everything: regulation of mitotic exit and cytokinesis by the MEN and SIN. Trends Cell Biol 11(2):89–95

    Article  CAS  PubMed  Google Scholar 

  4. Meitinger F, Palani S, Pereira G (2012) The power of MEN in cytokinesis. Cell Cycle 11(2):219–228. doi:10.4161/cc.11.2.18857

    Article  CAS  PubMed  Google Scholar 

  5. Queralt E, Uhlmann F (2008) Cdk-counteracting phosphatases unlock mitotic exit. Curr Opin Cell Biol 20(6):661–668. doi:10.1016/j.ceb.2008.09.003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Weiss EL (2012) Mitotic exit and separation of mother and daughter cells. Genetics 192(4):1165–1202. doi:10.1534/genetics.112.145516

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Thompson BJ, Sahai E (2015) MST kinases in development and disease. J Cell Biol 210(6):871–882. doi:10.1083/jcb.201507005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Hergovich A, Stegert MR, Schmitz D, Hemmings BA (2006) NDR kinases regulate essential cell processes from yeast to humans. Nat Rev Mol Cell Biol 7(4):253–264. doi:10.1038/nrm1891

    Article  CAS  PubMed  Google Scholar 

  9. Hergovich A (2011) MOB control: reviewing a conserved family of kinase regulators. Cell Signal 23(9):1433–1440. doi:10.1016/j.cellsig.2011.04.007

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Mocciaro A, Schiebel E (2010) Cdc14: a highly conserved family of phosphatases with non-conserved functions? J Cell Sci 123(Pt 17):2867–2876. doi:10.1242/jcs.074815

    Article  CAS  PubMed  Google Scholar 

  11. Hergovich A, Hemmings BA (2012) Hippo signalling in the G2/M cell cycle phase: lessons learned from the yeast MEN and SIN pathways. Semin Cell Dev Biol 23(7):794–802. doi:10.1016/j.semcdb.2012.04.001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Harvey KF, Zhang X, Thomas DM (2013) The Hippo pathway and human cancer. Nat Rev Cancer 13(4):246–257. doi:10.1038/nrc3458

    Article  CAS  PubMed  Google Scholar 

  13. Hong W, Guan KL (2012) The YAP and TAZ transcription co-activators: key downstream effectors of the mammalian Hippo pathway. Semin Cell Dev Biol 23(7):785–793. doi:10.1016/j.semcdb.2012.05.004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Johnson R, Halder G (2014) The two faces of Hippo: targeting the Hippo pathway for regenerative medicine and cancer treatment. Nat Rev Drug Discov 13(1):63–79. doi:10.1038/nrd4161

    Article  CAS  PubMed  Google Scholar 

  15. Moroishi T, Hansen CG, Guan KL (2015) The emerging roles of YAP and TAZ in cancer. Nat Rev Cancer 15(2):73–79. doi:10.1038/nrc3876

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Chan EH, Nousiainen M, Chalamalasetty RB, Schafer A, Nigg EA, Sillje HH (2005) The Ste20-like kinase Mst2 activates the human large tumor suppressor kinase Lats1. Oncogene 24(12):2076–2086. doi:10.1038/sj.onc.1208445

    Article  CAS  PubMed  Google Scholar 

  17. Hergovich A (2013) Regulation and functions of mammalian LATS/NDR kinases: looking beyond canonical Hippo signalling. Cell Biosci 3(1):32. doi:10.1186/2045-3701-3-32

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Hergovich A, Kohler RS, Schmitz D, Vichalkovski A, Cornils H, Hemmings BA (2009) The MST1 and hMOB1 tumor suppressors control human centrosome duplication by regulating NDR kinase phosphorylation. Curr Biol 19(20):1692–1702. doi:10.1016/j.cub.2009.09.020

    Article  CAS  PubMed  Google Scholar 

  19. Ni L, Zheng Y, Hara M, Pan D, Luo X (2015) Structural basis for Mob1-dependent activation of the core Mst-Lats kinase cascade in Hippo signaling. Genes Dev 29(13):1416–1431. doi:10.1101/gad.264929.115

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Tang F, Gill J, Ficht X, Barthlott T, Cornils H, Schmitz-Rohmer D, Hynx D, Zhou D, Zhang L, Xue G, Grzmil M, Yang Z, Hergovich A, Hollaender GA, Stein JV, Hemmings BA, Matthias P (2015) The kinases NDR1/2 act downstream of the Hippo homolog MST1 to mediate both egress of thymocytes from the thymus and lymphocyte motility. Sci Signal 8(397):ra100. doi:10.1126/scisignal.aab2425

    Article  CAS  PubMed  Google Scholar 

  21. Vichalkovski A, Gresko E, Cornils H, Hergovich A, Schmitz D, Hemmings BA (2008) NDR kinase is activated by RASSF1A/MST1 in response to Fas receptor stimulation and promotes apoptosis. Curr Biol 18(23):1889–1895. doi:10.1016/j.cub.2008.10.060

    Article  CAS  PubMed  Google Scholar 

  22. Zhou Y, Adolfs Y, Pijnappel WW, Fuller SJ, Van der Schors RC, Li KW, Sugden PH, Smit AB, Hergovich A, Pasterkamp RJ (2011) MICAL-1 is a negative regulator of MST-NDR kinase signaling and apoptosis. Mol Cell Biol 31(17):3603–3615. doi:10.1128/MCB.01389-10

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Lei QY, Zhang H, Zhao B, Zha ZY, Bai F, Pei XH, Zhao S, Xiong Y, Guan KL (2008) TAZ promotes cell proliferation and epithelial-mesenchymal transition and is inhibited by the hippo pathway. Mol Cell Biol 28(7):2426–2436. doi:10.1128/MCB.01874-07

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Liu CY, Zha ZY, Zhou X, Zhang H, Huang W, Zhao D, Li T, Chan SW, Lim CJ, Hong W, Zhao S, Xiong Y, Lei QY, Guan KL (2010) The hippo tumor pathway promotes TAZ degradation by phosphorylating a phosphodegron and recruiting the SCF{beta}-TrCP E3 ligase. J Biol Chem 285(48):37159–37169. doi:10.1074/jbc.M110.152942

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Zhao B, Li L, Tumaneng K, Wang CY, Guan KL (2010) A coordinated phosphorylation by Lats and CK1 regulates YAP stability through SCF(beta-TRCP). Genes Dev 24(1):72–85. doi:10.1101/gad.1843810

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Zhao B, Wei X, Li W, Udan RS, Yang Q, Kim J, Xie J, Ikenoue T, Yu J, Li L, Zheng P, Ye K, Chinnaiyan A, Halder G, Lai ZC, Guan KL (2007) Inactivation of YAP oncoprotein by the Hippo pathway is involved in cell contact inhibition and tissue growth control. Genes Dev 21(21):2747–2761. doi:10.1101/gad.1602907

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Dong J, Feldmann G, Huang J, Wu S, Zhang N, Comerford SA, Gayyed MF, Anders RA, Maitra A, Pan D (2007) Elucidation of a universal size-control mechanism in Drosophila and mammals. Cell 130(6):1120–1133. doi:10.1016/j.cell.2007.07.019

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Hao Y, Chun A, Cheung K, Rashidi B, Yang X (2008) Tumor suppressor LATS1 is a negative regulator of oncogene YAP. J Biol Chem 283(9):5496–5509. doi:10.1074/jbc.M709037200

    Article  CAS  PubMed  Google Scholar 

  29. Zhang L, Tang F, Terracciano L, Hynx D, Kohler R, Bichet S, Hess D, Cron P, Hemmings BA, Hergovich A, Schmitz-Rohmer D (2015) NDR functions as a physiological YAP1 kinase in the intestinal epithelium. Curr Biol 25(3):296–305. doi:10.1016/j.cub.2014.11.054

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Kim TS, Lee DH, Kim SK, Shin SY, Seo EJ, Lim DS (2012) Mammalian sterile 20-like kinase 1 suppresses lymphoma development by promoting faithful chromosome segregation. Cancer Res 72(20):5386–5395. doi:10.1158/0008-5472.CAN-11-3956

    Article  CAS  PubMed  Google Scholar 

  31. Kim M, Lee MS, Kim CH, Lim DS (2014) The MST1/2-SAV1 complex of the Hippo pathway promotes ciliogenesis. Nat Commun 5:5370. doi:10.1038/ncomms6370

    Article  CAS  PubMed  Google Scholar 

  32. Kim S, Tsiokas L (2011) Cilia and cell cycle re-entry: more than a coincidence. Cell Cycle 10(16):2683–2690

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Kobayashi T, Dynlacht BD (2011) Regulating the transition from centriole to basal body. J Cell Biol 193(3):435–444. doi:10.1083/jcb.201101005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Wilkinson DS, Jariwala JS, Anderson E, Mitra K, Meisenhelder J, Chang JT, Ideker T, Hunter T, Nizet V, Dillin A, Hansen M (2015) Phosphorylation of LC3 by the Hippo kinases STK3/STK4 is essential for autophagy. Mol Cell 57(1):55–68. doi:10.1016/j.molcel.2014.11.019

    Article  CAS  PubMed  Google Scholar 

  35. Maejima Y, Kyoi S, Zhai P, Liu T, Li H, Ivessa A, Sciarretta S, Del Re DP, Zablocki DK, Hsu CP, Lim DS, Isobe M, Sadoshima J (2013) Mst1 inhibits autophagy by promoting the interaction between Beclin1 and Bcl-2. Nat Med 19(11):1478–1488. doi:10.1038/nm.3322

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Domenech E, Maestre C, Esteban-Martinez L, Partida D, Pascual R, Fernandez-Miranda G, Seco E, Campos-Olivas R, Perez M, Megias D, Allen K, Lopez M, Saha AK, Velasco G, Rial E, Mendez R, Boya P, Salazar-Roa M, Malumbres M (2015) AMPK and PFKFB3 mediate glycolysis and survival in response to mitophagy during mitotic arrest. Nat Cell Biol 17(10):1304–1316. doi:10.1038/ncb3231

    Article  CAS  PubMed  Google Scholar 

  37. Hergovich A (2012) Mammalian Hippo signalling: a kinase network regulated by protein-protein interactions. Biochem Soc Trans 40(1):124–128. doi:10.1042/BST20110619

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Guo C, Tommasi S, Liu L, Yee JK, Dammann R, Pfeifer GP (2007) RASSF1A is part of a complex similar to the Drosophila Hippo/Salvador/Lats tumor-suppressor network. Curr Biol 17(8):700–705. doi:10.1016/j.cub.2007.02.055

    Article  CAS  PubMed  Google Scholar 

  39. Matallanas D, Romano D, Yee K, Meissl K, Kucerova L, Piazzolla D, Baccarini M, Vass JK, Kolch W, O'Neill E (2007) RASSF1A elicits apoptosis through an MST2 pathway directing proapoptotic transcription by the p73 tumor suppressor protein. Mol Cell 27(6):962–975. doi:10.1016/j.molcel.2007.08.008

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Jiang L, Rong R, Sheikh MS, Huang Y (2014) Mitotic arrest by tumor suppressor RASSF1A is regulated via CHK1 phosphorylation. Mol Cancer Res 12(1):119–129. doi:10.1158/1541-7786.MCR-13-0482

    Article  CAS  PubMed  Google Scholar 

  41. Donninger H, Clark JA, Monaghan MK, Schmidt ML, Vos M, Clark GJ (2014) Cell cycle restriction is more important than apoptosis induction for RASSF1A protein tumor suppression. J Biol Chem 289(45):31287–31295. doi:10.1074/jbc.M114.609537

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Pefani DE, Latusek R, Pires I, Grawenda AM, Yee KS, Hamilton G, van der Weyden L, Esashi F, Hammond EM, O'Neill E (2015) RASSF1A-LATS1 signalling stabilizes replication forks by restricting CDK2-mediated phosphorylation of BRCA2. Nat Cell Biol 17(4):531. doi:10.1038/ncb3152

    Article  CAS  PubMed  Google Scholar 

  43. 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. J Cell Biol 197(5):625–641. doi:10.1083/jcb.201110110

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Okamoto A, Yabuta N, Mukai S, Torigata K, Nojima H (2015) Phosphorylation of CHO1 by Lats1/2 regulates the centrosomal activation of LIMK1 during cytokinesis. Cell Cycle 14(10):1568–1582. doi:10.1080/15384101.2015.1026489

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Masuda K, Chiyoda T, Sugiyama N, Segura-Cabrera A, Kabe Y, Ueki A, Banno K, Suematsu M, Aoki D, Ishihama Y, Saya H, Kuninaka S (2015) LATS1 and LATS2 phosphorylate CDC26 to modulate assembly of the tetratricopeptide repeat subcomplex of APC/C. PLoS One 10(2), e0118662. doi:10.1371/journal.pone.0118662

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. McPherson JP, Tamblyn L, Elia A, Migon E, Shehabeldin A, Matysiak-Zablocki E, Lemmers B, Salmena L, Hakem A, Fish J, Kassam F, Squire J, Bruneau BG, Hande MP, Hakem R (2004) Lats2/Kpm is required for embryonic development, proliferation control and genomic integrity. EMBO J 23(18):3677–3688. doi:10.1038/sj.emboj.7600371

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Yabuta N, Mukai S, Okamoto A, Okuzaki D, Suzuki H, Torigata K, Yoshida K, Okada N, Miura D, Ito A, Ikawa M, Okabe M, Nojima H (2013) N-terminal truncation of Lats1 causes abnormal cell growth control and chromosomal instability. J Cell Sci 126(Pt 2):508–520. doi:10.1242/jcs.113431

    Article  CAS  PubMed  Google Scholar 

  48. Yabuta N, Okada N, Ito A, Hosomi T, Nishihara S, Sasayama Y, Fujimori A, Okuzaki D, Zhao H, Ikawa M, Okabe M, Nojima H (2007) Lats2 is an essential mitotic regulator required for the coordination of cell division. J Biol Chem 282(26):19259–19271. doi:10.1074/jbc.M608562200

    Article  CAS  PubMed  Google Scholar 

  49. Ganem NJ, Godinho SA, Pellman D (2009) A mechanism linking extra centrosomes to chromosomal instability. Nature 460(7252):278–282. doi:10.1038/nature08136

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Ganem NJ, Pellman D (2012) Linking abnormal mitosis to the acquisition of DNA damage. J Cell Biol 199(6):871–881. doi:10.1083/jcb.201210040

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Kwon M, Godinho SA, Chandhok NS, Ganem NJ, Azioune A, Thery M, Pellman D (2008) Mechanisms to suppress multipolar divisions in cancer cells with extra centrosomes. Genes Dev 22(16):2189–2203. doi:10.1101/gad.1700908

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Ganem NJ, Cornils H, Chiu SY, O'Rourke KP, Arnaud J, Yimlamai D, Thery M, Camargo FD, Pellman D (2014) Cytokinesis failure triggers hippo tumor suppressor pathway activation. Cell 158(4):833–848. doi:10.1016/j.cell.2014.06.029

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Du Z, Tong X, Ye X (2013) Cyclin D1 promotes cell cycle progression through enhancing NDR1/2 kinase activity independent of cyclin-dependent kinase 4. J Biol Chem 288(37):26678–26687. doi:10.1074/jbc.M113.466433

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Chiba S, Amagai Y, Homma Y, Fukuda M, Mizuno K (2013) NDR2-mediated Rabin8 phosphorylation is crucial for ciliogenesis by switching binding specificity from phosphatidylserine to Sec15. EMBO J 32(6):874–885. doi:10.1038/emboj.2013.32

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Hergovich A, Lamla S, Nigg EA, Hemmings BA (2007) Centrosome-associated NDR kinase regulates centrosome duplication. Mol Cell 25(4):625–634. doi:10.1016/j.molcel.2007.01.020

    Article  CAS  PubMed  Google Scholar 

  56. Goldstein O, Kukekova AV, Aguirre GD, Acland GM (2010) Exonic SINE insertion in STK38L causes canine early retinal degeneration (erd). Genomics 96(6):362–368. doi:10.1016/j.ygeno.2010.09.003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Chakraborty A, Prasanth KV, Prasanth SG (2014) Dynamic phosphorylation of HP1alpha regulates mitotic progression in human cells. Nat Commun 5:3445. doi:10.1038/ncomms4445

    PubMed  PubMed Central  Google Scholar 

  58. Chakraborty A, Prasanth SG (2014) Phosphorylation-dephosphorylation cycle of HP1alpha governs accurate mitotic progression. Cell Cycle 13(11):1663–1670. doi:10.4161/cc.29065

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Yan M, Chu L, Qin B, Wang Z, Liu X, Jin C, Zhang G, Gomez M, Hergovich A, Chen Z, He P, Gao X, Yao X (2015) Regulation of NDR1 activity by PLK1 ensures proper spindle orientation in mitosis. Sci Rep 5:10449. doi:10.1038/srep10449

    Article  PubMed  PubMed Central  Google Scholar 

  60. Fukasawa T, Enomoto A, Miyagawa K (2015) Serine-threonine kinase 38 regulates CDC25A stability and the DNA damage-induced G2/M checkpoint. Cell Signal 27(8):1569–1575. doi:10.1016/j.cellsig.2015.04.013

    Article  CAS  PubMed  Google Scholar 

  61. Schmitz-Rohmer D, Probst S, Yang ZZ, Laurent F, Stadler MB, Zuniga A, Zeller R, Hynx D, Hemmings BA, Hergovich A (2015) NDR kinases are essential for somitogenesis and cardiac looping during mouse embryonic development. PLoS One 10(8), e0136566. doi:10.1371/journal.pone.0136566

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Joffre C, Dupont N, Hoa L, Gomez V, Pardo R, Goncalves-Pimentel C, Achard P, Bettoun A, Meunier B, Bauvy C, Cascone I, Codogno P, Fanto M, Hergovich A, Camonis J (2015) The pro-apoptotic STK38 kinase is a new beclin1 partner positively regulating autophagy. Curr Biol 25(19):2479–2492. doi:10.1016/j.cub.2015.08.031

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Wu Z, Sawada T, Shiba K, Liu S, Kanao T, Takahashi R, Hattori N, Imai Y, Lu B (2013) Tricornered/NDR kinase signaling mediates PINK1-directed mitochondrial quality control and tissue maintenance. Genes Dev 27(2):157–162. doi:10.1101/gad.203406.112

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Cook D, Hoa LY, Gomez V, Gomez M, Hergovich A (2014) Constitutively active NDR1-PIF kinase functions independent of MST1 and hMOB1 signalling. Cell Signal 26(8):1657–1667. doi:10.1016/j.cellsig.2014.04.011

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Stegert MR, Tamaskovic R, Bichsel SJ, Hergovich A, Hemmings BA (2004) Regulation of NDR2 protein kinase by multi-site phosphorylation and the S100B calcium-binding protein. J Biol Chem 279(22):23806–23812. doi:10.1074/jbc.M402472200

    Article  CAS  PubMed  Google Scholar 

  66. Ultanir SK, Hertz NT, Li G, Ge WP, Burlingame AL, Pleasure SJ, Shokat KM, Jan LY, Jan YN (2012) Chemical genetic identification of NDR1/2 kinase substrates AAK1 and Rabin8 Uncovers their roles in dendrite arborization and spine development. Neuron 73(6):1127–1142. doi:10.1016/j.neuron.2012.01.019

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Wilmeth LJ, Shrestha S, Montano G, Rashe J, Shuster CB (2010) Mutual dependence of Mob1 and the chromosomal passenger complex for localization during mitosis. Mol Biol Cell 21(3):380–392. doi:10.1091/mbc.E09-06-0471

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Florindo C, Perdigao J, Fesquet D, Schiebel E, Pines J, Tavares AA (2012) Human Mob1 proteins are required for cytokinesis by controlling microtubule stability. J Cell Sci 125(Pt 13):3085–3090. doi:10.1242/jcs.097147

    Article  CAS  PubMed  Google Scholar 

  69. Nishio M, Hamada K, Kawahara K, Sasaki M, Noguchi F, Chiba S, Mizuno K, Suzuki SO, Dong Y, Tokuda M, Morikawa T, Hikasa H, Eggenschwiler J, Yabuta N, Nojima H, Nakagawa K, Hata Y, Nishina H, Mimori K, Mori M, Sasaki T, Mak TW, Nakano T, Itami S, Suzuki A (2012) Cancer susceptibility and embryonic lethality in Mob1a/1b double-mutant mice. J Clin Invest 122(12):4505–4518. doi:10.1172/JCI63735

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Rock JM, Lim D, Stach L, Ogrodowicz RW, Keck JM, Jones MH, Wong CC, Yates JR 3rd, Winey M, Smerdon SJ, Yaffe MB, Amon A (2013) Activation of the yeast Hippo pathway by phosphorylation-dependent assembly of signaling complexes. Science 340(6134):871–875. doi:10.1126/science.1235822

    Article  CAS  PubMed  Google Scholar 

  71. Gogl G, Schneider KD, Yeh BJ, Alam N, Nguyen Ba AN, Moses AM, Hetenyi C, Remenyi A, Weiss EL (2015) The structure of an NDR/LATS kinase-Mob complex reveals a novel kinase-coactivator system and substrate docking mechanism. PLoS Biol 13(5), e1002146. doi:10.1371/journal.pbio.1002146

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Ji M, Yang S, Chen Y, Xiao L, Zhang L, Dong J (2012) Phospho-regulation of KIBRA by CDK1 and CDC14 phosphatase controls cell-cycle progression. Biochem J 447(1):93–102. doi:10.1042/BJ20120751

    Article  CAS  PubMed  Google Scholar 

  73. Zhang L, Yang S, Wennmann DO, Chen Y, Kremerskothen J, Dong J (2014) KIBRA: in the brain and beyond. Cell Signal 26(7):1392–1399. doi:10.1016/j.cellsig.2014.02.023

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Kao L, Wang YT, Chen YC, Tseng SF, Jhang JC, Chen YJ, Teng SC (2014) Global analysis of cdc14 dephosphorylation sites reveals essential regulatory role in mitosis and cytokinesis. Mol Cell Proteomics 13(2):594–605. doi:10.1074/mcp.M113.032680

    Article  CAS  PubMed  Google Scholar 

  75. Chen JS, Broadus MR, McLean JR, Feoktistova A, Ren L, Gould KL (2013) Comprehensive proteomics analysis reveals new substrates and regulators of the fission yeast clp1/cdc14 phosphatase. Mol Cell Proteomics 12(5):1074–1086. doi:10.1074/mcp.M112.025924

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Baro B, Rodriguez-Rodriguez JA, Calabria I, Hernaez ML, Gil C, Queralt E (2013) Dual regulation of the mitotic exit network (MEN) by PP2A-Cdc55 phosphatase. PLoS Genet 9(12), e1003966. doi:10.1371/journal.pgen.1003966

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Grallert A, Boke E, Hagting A, Hodgson B, Connolly Y, Griffiths JR, Smith DL, Pines J, Hagan IM (2015) A PP1-PP2A phosphatase relay controls mitotic progression. Nature 517(7532):94–98. doi:10.1038/nature14019

    Article  CAS  PubMed  Google Scholar 

  78. Cundell MJ, Bastos RN, Zhang T, Holder J, Gruneberg U, Novak B, Barr FA (2013) The BEG (PP2A-B55/ENSA/Greatwall) pathway ensures cytokinesis follows chromosome separation. Mol Cell 52(3):393–405. doi:10.1016/j.molcel.2013.09.005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Yang S, Zhang L, Liu M, Chong R, Ding SJ, Chen Y, Dong J (2013) CDK1 phosphorylation of YAP promotes mitotic defects and cell motility and is essential for neoplastic transformation. Cancer Res 73(22):6722–6733. doi:10.1158/0008-5472.CAN-13-2049

    Article  CAS  PubMed  Google Scholar 

  80. Zhang L, Chen X, Stauffer S, Yang S, Chen Y, Dong J (2015) CDK1 phosphorylation of TAZ in mitosis inhibits its oncogenic activity. Oncotarget 6(31):31399–31412. doi:10.18632/oncotarget.5189

    PubMed  PubMed Central  Google Scholar 

  81. Yang S, Zhang L, Chen X, Chen Y, Dong J (2015) Oncoprotein YAP regulates the spindle checkpoint activation in a mitotic phosphorylation-dependent manner through up-regulation of BubR1. J Biol Chem 290(10):6191–6202. doi:10.1074/jbc.M114.624411

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Zanconato F, Forcato M, Battilana G, Azzolin L, Quaranta E, Bodega B, Rosato A, Bicciato S, Cordenonsi M, Piccolo S (2015) Genome-wide association between YAP/TAZ/TEAD and AP-1 at enhancers drives oncogenic growth. Nat Cell Biol 17(9):1218–1227. doi:10.1038/ncb3216

    Article  CAS  PubMed  Google Scholar 

  83. Wehr MC, Holder MV, Gailite I, Saunders RE, Maile TM, Ciirdaeva E, Instrell R, Jiang M, Howell M, Rossner MJ, Tapon N (2013) Salt-inducible kinases regulate growth through the Hippo signalling pathway in Drosophila. Nat Cell Biol 15(1):61–71. doi:10.1038/ncb2658

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Ahmed AA, Lu Z, Jennings NB, Etemadmoghadam D, Capalbo L, Jacamo RO, Barbosa-Morais N, Le XF, Vivas-Mejia P, Lopez-Berestein G, Grandjean G, Bartholomeusz G, Liao W, Andreeff M, Bowtell D, Glover DM, Sood AK, Bast RC Jr (2010) SIK2 is a centrosome kinase required for bipolar mitotic spindle formation that provides a potential target for therapy in ovarian cancer. Cancer Cell 18(2):109–121. doi:10.1016/j.ccr.2010.06.018

    Article  CAS  PubMed  Google Scholar 

  85. Chen H, Huang S, Han X, Zhang J, Shan C, Tsang YH, Ma HT, Poon RY (2014) Salt-inducible kinase 3 is a novel mitotic regulator and a target for enhancing antimitotic therapeutic-mediated cell death. Cell Death Dis 5, e1177. doi:10.1038/cddis.2014.154

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Couzens AL, Knight JD, Kean MJ, Teo G, Weiss A, Dunham WH, Lin ZY, Bagshaw RD, Sicheri F, Pawson T, Wrana JL, Choi H, Gingras AC (2013) Protein interaction network of the mammalian Hippo pathway reveals mechanisms of kinase-phosphatase interactions. Sci Signal 6(302):rs15. doi:10.1126/scisignal.2004712

    Article  CAS  PubMed  Google Scholar 

  87. Hauri S, Wepf A, van Drogen A, Varjosalo M, Tapon N, Aebersold R, Gstaiger M (2013) Interaction proteome of human Hippo signaling: modular control of the co-activator YAP1. Mol Syst Biol 9:713. doi:10.1002/msb.201304750

    Article  PubMed  PubMed Central  Google Scholar 

  88. Kohli P, Bartram MP, Habbig S, Pahmeyer C, Lamkemeyer T, Benzing T, Schermer B, Rinschen MM (2014) Label-free quantitative proteomic analysis of the YAP/TAZ interactome. Am J Physiol Cell Physiol 306(9):C805–C818. doi:10.1152/ajpcell.00339.2013

    Article  CAS  PubMed  Google Scholar 

  89. Kwon Y, Vinayagam A, Sun X, Dephoure N, Gygi SP, Hong P, Perrimon N (2013) The Hippo signaling pathway interactome. Science 342(6159):737–740. doi:10.1126/science.1243971

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Moya IM, Halder G (2014) Discovering the Hippo pathway protein-protein interactome. Cell Res 24(2):137–138. doi:10.1038/cr.2014.6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Wang W, Li X, Huang J, Feng L, Dolinta KG, Chen J (2014) Defining the protein-protein interaction network of the human hippo pathway. Mol Cell Proteomics 13(1):119–131. doi:10.1074/mcp.M113.030049

    Article  CAS  PubMed  Google Scholar 

  92. Madaule P, Eda M, Watanabe N, Fujisawa K, Matsuoka T, Bito H, Ishizaki T, Narumiya S (1998) Role of citron kinase as a target of the small GTPase Rho in cytokinesis. Nature 394(6692):491–494. doi:10.1038/28873

    Article  CAS  PubMed  Google Scholar 

  93. Golsteyn RM, Lane HA, Mundt KE, Arnaud L, Nigg EA (1996) The family of polo-like kinases. Prog Cell Cycle Res 2:107–114

    CAS  PubMed  Google Scholar 

  94. Lindqvist A, Rodriguez-Bravo V, Medema RH (2009) The decision to enter mitosis: feedback and redundancy in the mitotic entry network. J Cell Biol 185(2):193–202. doi:10.1083/jcb.200812045

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Keder A, Rives-Quinto N, Aerne BL, Franco M, Tapon N, Carmena A (2015) The hippo pathway core cassette regulates asymmetric cell division. Curr Biol 25(21):2739–2750. doi:10.1016/j.cub.2015.08.064

    Article  CAS  PubMed  Google Scholar 

  96. Dewey EB, Sanchez D, Johnston CA (2015) Warts phosphorylates mud to promote pins-mediated mitotic spindle orientation in Drosophila, independent of Yorkie. Curr Biol 25(21):2751–2762. doi:10.1016/j.cub.2015.09.025

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Bui DA, Lee W, White AE, Harper JW, Schackmann RC, Overholtzer M, Selfors LM, Brugge JS (2016) Cytokinesis involves a nontranscriptional function of the Hippo pathway effector YAP. Sci Signal 9(417):ra23. doi:10.1126/scisignal.aaa9227

    Article  PubMed  Google Scholar 

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Acknowledgements

We apologize to all authors whose work we could not cite due to space limitations. We are very grateful to Joanna Lisztwan and all members of the Hergovich laboratory for their critical review of the manuscript. The work of the Hergovich laboratory is supported by Cancer Research UK UCL Centre development funding, and the National Institute for Health Research University College London Hospitals Biomedical Research Centre.

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  1. Tumour Suppressor Signalling Networks Laboratory, UCL Cancer Institute, University College London, 72 Huntley Street, London, WC1E 6BT, UK

    Alexander Hergovich

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  1. Alexander Hergovich
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Correspondence to Alexander Hergovich .

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  1. CABIMER, Sevilla, Spain

    Fernando Monje-Casas

  2. Cancer Epigenetics & Biology Program, IDIBELL Hospitalet de Llobregat, Barcelona, Spain

    Ethel Queralt

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Hergovich, A. (2017). Hippo Signaling in Mitosis: An Updated View in Light of the MEN Pathway. In: Monje-Casas, F., Queralt, E. (eds) The Mitotic Exit Network. Methods in Molecular Biology, vol 1505. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-6502-1_19

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  • DOI: https://doi.org/10.1007/978-1-4939-6502-1_19

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