Non-canonical roles for the hippo pathway

The Hippo Signaling Pathway and Cancer

Volumn , Issue , 2013, Pages 327-346

  Varelas, Xaralabos ^a  

^a BOSTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Apoptosis; Cell cycle; Cilia; Hippo; Notch; PCP; Polarity; TAZ; TGF ; Ubiquitin; Wnt; YAP

Indexed keywords

EID: 84949176334     PISSN: None     EISSN: None     Source Type: Book    
DOI: 10.1007/978-1-4614-6220-0_17     Document Type: Chapter

References (108)

1. Alarcon C, Zaromytidou AI, Xi Q, Gao S, Yu J, Fujisawa S, et al. Nuclear CDKs drive Smad transcriptional activation and turnover in BMP and TGF-beta pathways. Cell. 2009;139(4):757-69. doi: 10.1016/j.cell.2009.09.035.
2. Aragon E, Goerner N, Zaromytidou AI, Xi Q, Escobedo A, Massague J, et al. A Smad action turnover switch operated by WW domain readers of a phosphoserine code. Genes Dev. 2011;25(12):1275-88. doi: 10.1101/gad.2060811.
3. Assemat E, Bazellieres E, Pallesi-Pocachard E, Le Bivic A, Massey-Harroche D. Polarity complex proteins. Biochim Biophys Acta. 2008;1778(3):614-30. doi: 10.1016/j.bbamem.2007.08.029.
4. Attisano L, Wrana JL. Signal transduction by the TGF-beta superfamily. Science. 2002;296(5573):1646-7. doi: 10.1126/science.1071809.
5. Aylon Y, Michael D, Shmueli A, Yabuta N, Nojima H, Oren M. A positive feedback loop between the p53 and Lats2 tumor suppressors prevents tetraploidization. Genes Dev. 2006;20(19): 2687-700. doi: 10.1101/gad.1447006.
6. Aylon Y, Ofir-Rosenfeld Y, Yabuta N, Lapi E, Nojima H, Lu X, et al. The Lats2 tumor suppressor augments p53-mediated apoptosis by promoting the nuclear proapoptotic function of ASPP1. Genes Dev. 2010;24(21):2420-9. doi: 10.1101/gad.1954410.
7. Baumgartner R, Poernbacher I, Buser N, Hafen E, Stocker H. The WW domain protein Kibra acts upstream of Hippo in Drosophila. Dev Cell. 2010;18(2):309-16. doi: 10.1016/j.devcel.2009.12.013.
8. Benhamouche S, Curto M, Saotome I, Gladden AB, Liu CH, Giovannini M, et al. Nf2/Merlin controls progenitor homeostasis and tumorigenesis in the liver. Genes Dev. 2010;24(16): 1718-30. doi: 10.1101/gad.1938710.
9. Brown KA, Aakre ME, Gorska AE, Price JO, Eltom SE, Pietenpol JA, et al. Induction by transforming growth factor-beta1 of epithelial to mesenchymal transition is a rare event in vitro. Breast Cancer Res. 2004;6(3):R215-31. doi: 10.1186/bcr778.
10. Buther K, Plaas C, Barnekow A, Kremerskothen J. KIBRA is a novel substrate for protein kinase Czeta. Biochem Biophys Res Commun. 2004;317(3):703-7. doi: 10.1016/j.bbrc.2004.03.107.
11. Camargo FD, Gokhale S, Johnnidis JB, Fu D, Bell GW, Jaenisch R, et al. YAP1 increases organ size and expands undifferentiated progenitor cells. Curr Biol. 2007;17(23):2054-60. doi: 10.1016/j.cub.2007.10.039.
12. Chan SW, Lim CJ, Chong YF, Pobbati AV, Huang C, Hong W. Hippo pathway-independent restriction of TAZ and YAP by angiomotin. J Biol Chem. 2011;286(9):7018-26. doi: 10.1074/jbc.C110.212621.
13. Cheung WL, Ajiro K, Samejima K, Kloc M, Cheung P, Mizzen CA, et al. Apoptotic phosphorylation of histone H2B is mediated by mammalian sterile twenty kinase. Cell. 2003;113(4): 507-17.
14. Chiyoda T, Sugiyama N, Shimizu T, Naoe H, Kobayashi Y, Ishizawa J, et al. LATS1/WARTS phosphorylates MYPT1 to counteract PLK1 and regulate mammalian mitotic progression. J Cell Biol. 2012;197(5):625-41. doi: 10.1083/jcb.201110110.
15. Cho E, Feng Y, Rauskolb C, Maitra S, Fehon R, Irvine KD. Delineation of a Fat tumor suppressor pathway. Nat Genet. 2006;38(10):1142-50. doi: 10.1038/ng1887.
16. Ciani L, Patel A, Allen ND, Ffrench-Constant C. Mice lacking the giant protocadherin mFAT1 exhibit renal slit junction abnormalities and a partially penetrant cyclopia and anophthalmia phenotype. Mol Cell Biol. 2003;23(10):3575-82.
17. Clark HF, Brentrup D, Schneitz K, Bieber A, Goodman C, Noll M. Dachsous encodes a member of the cadherin superfamily that controls imaginal disc morphogenesis in Drosophila. Genes Dev. 1995;9(12):1530-42.
18. Clevers H, Nusse R. Wnt/beta-catenin signaling and disease. Cell. 2012;149(6):1192-205. doi: 10.1016/j.cell.2012.05.012.
19. Corbit KC, Shyer AE, Dowdle WE, Gaulden J, Singla V, Chen MH, et al. Kif3a constrains betacatenin-dependent Wnt signalling through dual ciliary and non-ciliary mechanisms. Nat Cell Biol. 2008;10(1):70-6. doi: 10.1038/ncb1670.
20. Cordenonsi M, Zanconato F, Azzolin L, Forcato M, Rosato A, Frasson C, et al. The Hippo transducer TAZ confers cancer stem cell-related traits on breast cancer cells. Cell. 2011;147(4): 759-72. doi: 10.1016/j.cell.2011.09.048.
21. Duning K, Schurek EM, Schluter M, Bayer M, Reinhardt HC, Schwab A, et al. KIBRA modulates directional migration of podocytes. J Am Soc Nephrol. 2008;19(10):1891-903. doi: 10.1681/ASN.2007080916.
22. Dunn NR, Vincent SD, Oxburgh L, Robertson EJ, Bikoff EK. Combinatorial activities of Smad2 and Smad3 regulate mesoderm formation and patterning in the mouse embryo. Development. 2004;131(8):1717-28. doi: 10.1242/dev.01072.
23. Ernkvist M, Luna Persson N, Audebert S, Lecine P, Sinha I, Liu M, et al. The Amot/Patj/Syx signaling complex spatially controls RhoA GTPase activity in migrating endothelial cells. Blood. 2009;113(1):244-53. doi: 10.1182/blood-2008-04-153874.
24. Feng Y, Irvine KD. Processing and phosphorylation of the Fat receptor. Proc Natl Acad Sci U S A. 2009;106(29):11989-94. doi: 10.1073/pnas.0811540106.
25. Ferrigno O, Lallemand F, Verrecchia F, L'Hoste S, Camonis J, AtfiA, et al. Yes-associated protein (YAP65) interacts with Smad7 and potentiates its inhibitory activity against TGF-beta/Smad signaling. Oncogene. 2002;21(32):4879-84. doi: 10.1038/sj.onc.1205623.
26. Fujii M, Toyoda T, Nakanishi H, Yatabe Y, Sato A, Matsudaira Y, et al. TGF-beta synergizes with defects in the Hippo pathway to stimulate human malignant mesothelioma growth. J Exp Med. 2012;209(3):479-94. doi: 10.1084/jem.20111653.
27. Genevet A, Polesello C, Blight K, Robertson F, Collinson LM, Pichaud F, et al. The Hippo pathway regulates apical-domain size independently of its growth-control function. J Cell Sci. 2009;122(Pt 14):2360-70. doi: 10.1242/jcs.041806.
28. Genevet A, Wehr MC, Brain R, Thompson BJ, Tapon N. Kibra is a regulator of the Salvador/Warts/Hippo signaling network. Dev Cell. 2010;18(2):300-8. doi: 10.1016/j.devcel.2009.12.011.
29. Gladden AB, Hebert AM, Schneeberger EE, McClatchey AI. The NF2 tumor suppressor, Merlin, regulates epidermal development through the establishment of a junctional polarity complex. Dev Cell. 2010;19(5):727-39. doi: 10.1016/j.devcel.2010.10.008.
30. Goetz SC, Anderson KV. The primary cilium: a signalling centre during vertebrate development. Nat Rev Genet. 2010;11(5):331-44. doi: 10.1038/nrg2774.
31. Graves JD, Gotoh Y, Draves KE, Ambrose D, Han DK, Wright M, et al. Caspase-mediated activation and induction of apoptosis by the mammalian Ste20-like kinase Mst1. EMBO J. 1998;17(8):2224-34. doi: 10.1093/emboj/17.8.2224.
32. Habbig S, Bartram MP, Muller RU, Schwarz R, Andriopoulos N, Chen S, et al. NPHP4, a ciliaassociated protein, negatively regulates the Hippo pathway. J Cell Biol. 2011;193(4):633-42. doi: 10.1083/jcb.201009069.
33. Hamaratoglu F, Willecke M, Kango-Singh M, Nolo R, Hyun E, Tao C, et al. The tumour-suppressor genes NF2/Merlin and Expanded act through Hippo signalling to regulate cell proliferation and apoptosis. Nat Cell Biol. 2006;8(1):27-36. doi: 10.1038/ncb1339.
34. Hamaratoglu F, Gajewski K, Sansores-Garcia L, Morrison C, Tao C, Halder G. The Hippo tumorsuppressor pathway regulates apical-domain size in parallel to tissue growth. J Cell Sci. 2009;122(Pt 14):2351-9. doi: 10.1242/jcs.046482.
35. Harvey K, Tapon N. The Salvador-Warts-Hippo pathway-an emerging tumour-suppressor network. Nat Rev Cancer. 2007;7(3):182-91. doi: 10.1038/nrc2070.
36. Hashimoto M, Shinohara K, Wang J, Ikeuchi S, Yoshiba S, Meno C, et al. Planar polarization of node cells determines the rotational axis of node cilia. Nat Cell Biol. 2010;12(2):170-6. doi: 10.1038/ncb2020.
37. Heallen T, Zhang M, Wang J, Bonilla-Claudio M, Klysik E, Johnson RL, et al. Hippo pathway inhibits Wnt signaling to restrain cardiomyocyte proliferation and heart size. Science. 2011;332(6028):458-61. doi: 10.1126/science.1199010.
38. Hiemer SE, Varelas X. Stem cell regulation by the Hippo pathway. Biochim Biophys Acta. 2012 Jul 20. [Epub ahead of print]. PMID: 22824335.
39. Hossain Z, Ali SM, Ko HL, Xu J, Ng CP, Guo K, et al. Glomerulocystic kidney disease in mice with a targeted inactivation of Wwtr1. Proc Natl Acad Sci U S A. 2007;104(5):1631-6. doi: 10.1073/pnas.0605266104.
40. Imajo M, Miyatake K, Iimura A, Miyamoto A, Nishida E. A molecular mechanism that links Hippo signalling to the inhibition of Wnt/beta-catenin signalling. EMBO J. 2012;31(5):1109-22. doi: 10.1038/emboj.2011.487.
41. Ingham RJ, Gish G, Pawson T. The Nedd4 family of E3 ubiquitin ligases: functional diversity within a common modular architecture. Oncogene. 2004;23(11):1972-84. doi: 10.1038/sj.onc.1207436.
42. Ishiuchi T, Misaki K, Yonemura S, Takeichi M, Tanoue T. Mammalian Fat and Dachsous cadherins regulate apical membrane organization in the embryonic cerebral cortex. J Cell Biol. 2009;185(6):959-67. doi: 10.1083/jcb.200811030.
43. Kang HS, Beak JY, Kim YS, Herbert R, Jetten AM. Glis3 is associated with primary cilia and Wwtr1/TAZ and implicated in polycystic kidney disease. Mol Cell Biol. 2009;29(10):2556-69. doi: 10.1128/MCB.01620-08.
44. Lallemand D, Curto M, Saotome I, Giovannini M, McClatchey AI. NF2 deficiency promotes tumorigenesis and metastasis by destabilizing adherens junctions. Genes Dev. 2003;17(9): 1090-100. doi: 10.1101/gad.1054603.
45. Lehtinen MK, Yuan Z, Boag PR, Yang Y, Villen J, Becker EB, et al. A conserved MST-FOXO signaling pathway mediates oxidative-stress responses and extends life span. Cell. 2006;125(5):987-1001. doi: 10.1016/j.cell.2006.03.046.
46. Levy D, Adamovich Y, Reuven N, Shaul Y. The Yes-associated protein 1 stabilizes p73 by preventing Itch-mediated ubiquitination of p73. Cell Death Differ. 2007;14(4):743-51. doi: 10.1038/sj.cdd.4402063.
47. Liu-Chittenden Y, Huang B, Shim JS, Chen Q, Lee SJ, Anders RA, et al. Genetic and pharmacological disruption of the TEAD-YAP complex suppresses the oncogenic activity of YAP. Genes Dev. 2012;26(12):1300-5. doi: 10.1101/gad.192856.112.
48. Maitra S, Kulikauskas RM, Gavilan H, Fehon RG. The tumor suppressors Merlin and Expanded function cooperatively to modulate receptor endocytosis and signaling. Curr Biol. 2006;16(7):702-9. doi: 10.1016/j.cub.2006.02.063.
49. Makita R, Uchijima Y, Nishiyama K, Amano T, Chen Q, Takeuchi T, et al. Multiple renal cysts, urinary concentration defects, and pulmonary emphysematous changes in mice lacking TAZ. Am J Physiol Renal Physiol. 2008;294(3):F542-53. doi: 10.1152/ajprenal.00201.2007.
50. Makuch L, Volk L, Anggono V, Johnson RC, Yu Y, Duning K, et al. Regulation of AMPA receptor function by the human memory-associated gene KIBRA. Neuron. 2011;71(6):1022-9. doi: 10.1016/j.neuron.2011.08.017.
51. Mani SA, Guo W, Liao MJ, Eaton EN, Ayyanan A, Zhou AY, et al. The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell. 2008;133(4):704-15. doi: 10.1016/j.cell.2008.03.027.
52. Mardin BR, Lange C, Baxter JE, Hardy T, Scholz SR, Fry AM, et al. Components of the Hippo pathway cooperate with Nek2 kinase to regulate centrosome disjunction. Nat Cell Biol. 2010;12(12):1166-76. doi: 10.1038/ncb2120.
53. Matakatsu H, Blair SS. Separating planar cell polarity and Hippo pathway activities of the protocadherins Fat and Dachsous. Development. 2012;139(8):1498-508. doi: 10.1242/dev.070367.
54. Matallanas D, Romano D, Yee K, Meissl K, Kucerova L, Piazzolla D, et al. RASSF1A elicits apoptosis through an MST2 pathway directing proapoptotic transcription by the p73 tumor suppressor protein. Mol Cell. 2007;27(6):962-75. doi: 10.1016/j.molcel.2007.08.008.
55. Mauviel A, Nallet-Staub F, Varelas X. Integrating developmental signals: a Hippo in the (path) way. Oncogene. 2012;31(14):1743-56. doi: 10.1038/onc.2011.363.
56. Meignin C, Alvarez-Garcia I, Davis I, Palacios IM. The salvador-warts-hippo pathway is required for epithelial proliferation and axis specification in Drosophila. Curr Biol. 2007;17(21): 1871-8. doi: 10.1016/j.cub.2007.09.062.
57. Mesnard D, Guzman-Ayala M, Constam DB. Nodal specifies embryonic visceral endoderm and sustains pluripotent cells in the epiblast before overt axial patterning. Development. 2006;133(13):2497-505. doi: 10.1242/dev.02413.
58. Nauli SM, Alenghat FJ, Luo Y, Williams E, Vassilev P, Li X, et al. Polycystins 1 and 2 mediate mechanosensation in the primary cilium of kidney cells. Nat Genet. 2003;33(2):129-37. doi: 10.1038/ng1076.
59. Oh HJ, Kim MJ, Song SJ, Kim T, Lee D, Kwon SH, et al. MST1 limits the kinase activity of aurora B to promote stable kinetochore-microtubule attachment. Curr Biol. 2010;20(5):416-22. doi: 10.1016/j.cub.2009.12.054.
60. Pan D. The hippo signaling pathway in development and cancer. Dev Cell. 2010;19(4):491-505. doi: 10.1016/j.devcel.2010.09.011.
61. Papassotiropoulos A, Stephan DA, Huentelman MJ, Hoerndli FJ, Craig DW, Pearson JV, et al. Common Kibra alleles are associated with human memory performance. Science. 2006;314(5798):475-8. doi: 10.1126/science.1129837.
62. Park TJ, Mitchell BJ, Abitua PB, Kintner C, Wallingford JB. Dishevelled controls apical docking and planar polarization of basal bodies in ciliated epithelial cells. Nat Genet. 2008;40(7): 871-9. doi: 10.1038/ng.104.
63. Petridou S, Maltseva O, Spanakis S, Masur SK. TGF-beta receptor expression and smad2 localization are cell density dependent infibroblasts. Invest Ophthalmol Vis Sci. 2000;41(1):89-95.
64. Pisarska MD, Kuo FT, Bentsi-Barnes IK, Khan S, Barlow GM. LATS1 phosphorylates forkhead L2 and regulates its transcriptional activity. Am J Physiol Endocrinol Metab. 2010;299(1): E101-9. doi: 10.1152/ajpendo.00534.2009.
65. Polesello C, Tapon N. Salvador-warts-hippo signaling promotes Drosophila posterior follicle cell maturation downstream of notch. Curr Biol. 2007;17(21):1864-70. doi: 10.1016/j.cub.2007.09.049.
66. Reddy BV, Rauskolb C, Irvine KD. In fl uence of fat-hippo and notch signaling on the proliferation and differentiation of Drosophila optic neuroepithelia. Development. 2010;137(14):2397-408. doi: 10.1242/dev.050013.
67. Saburi S, Hester I, Fischer E, Pontoglio M, Eremina V, Gessler M, et al. Loss of Fat4 disrupts PCP signaling and oriented cell division and leads to cystic kidney disease. Nat Genet. 2008;40(8):1010-5. doi: 10.1038/ng.179.
68. Saburi S, Hester I, Goodrich L, McNeill H. Functional interactions between Fat family cadherins in tissue morphogenesis and planar polarity. Development. 2012;139(10):1806-20. doi: 10.1242/dev.077461.
69. Salih DA, Brunet A. FoxO transcription factors in the maintenance of cellular homeostasis during aging. Curr Opin Cell Biol. 2008;20(2):126-36. doi: 10.1016/j.ceb.2008.02.005.
70. Schlegelmilch K, Mohseni M, Kirak O, Pruszak J, Rodriguez JR, Zhou D, et al. Yap1 acts downstream of alpha-catenin to control epidermal proliferation. Cell. 2011;144(5):782-95. doi: 10.1016/j.cell.2011.02.031.
71. Shin K, Fogg VC, Margolis B. Tight junctions and cell polarity. Annu Rev Cell Dev Biol. 2006;22:207-35. doi: 10.1146/annurev.cellbio.22.010305.104219.
72. Shin K, Wang Q, Margolis B. PATJ regulates directional migration of mammalian epithelial cells. EMBO Rep. 2007;8(2):158-64. doi: 10.1038/sj.embor.7400890.
73. Sopko R, McNeill H. The skinny on Fat: an enormous cadherin that regulates cell adhesion, tissue growth, and planar cell polarity. Curr Opin Cell Biol. 2009;21(5):717-23. doi: 10.1016/j.ceb.2009.07.001.
74. Sopko R, Silva E, Clayton L, Gardano L, Barrios-Rodiles M, Wrana J, et al. Phosphorylation of the tumor suppressor fat is regulated by its ligand Dachsous and the kinase discs overgrown. Curr Biol. 2009;19(13):1112-7. doi: 10.1016/j.cub.2009.05.049.
75. Staudinger J, Lu J, Olson EN. Specific interaction of the PDZ domain protein PICK1 with the COOH terminus of protein kinase C-alpha. J Biol Chem. 1997;272(51):32019-24.
76. Tao W, Zhang S, Turenchalk GS, Stewart RA, St John MA, Chen W, et al. Human homologue of the Drosophila melanogaster lats tumour suppressor modulates CDC2 activity. Nat Genet. 1999;21(2):177-81. doi: 10.1038/5960.
77. Taylor LK, Wang HC, Erikson RL. Newly identified stress-responsive protein kinases, Krs-1 and Krs-2. Proc Natl Acad Sci U S A. 1996;93(19):10099-104.
78. Thiery JP, Acloque H, Huang RY, Nieto MA. Epithelial-mesenchymal transitions in development and disease. Cell. 2009;139(5):871-90. doi: 10.1016/j.cell.2009.11.007.
79. Thomas C, Strutt D. The roles of the cadherins Fat and Dachsous in planar polarity specification in Drosophila. Dev Dyn. 2012;241(1):27-39. doi: 10.1002/dvdy.22736.
80. Tian Y, Kolb R, Hong JH, Carroll J, Li D, You J, et al. TAZ promotes PC2 degradation through a SCFbeta-Trcp E3 ligase complex. Mol Cell Biol. 2007;27(18):6383-95. doi: 10.1128/MCB.00254-07.
81. Toji S, Yabuta N, Hosomi T, Nishihara S, Kobayashi T, Suzuki S, et al. The centrosomal protein Lats2 is a phosphorylation target of Aurora-A kinase. Genes Cells. 2004;9(5):383-97. doi: 10.1111/j.1356-9597.2004.00732.x.
82. Tschop K, Conery AR, Litovchick L, Decaprio JA, Settleman J, Harlow E, et al. A kinase shRNA screen links LATS2 and the pRB tumor suppressor. Genes Dev. 2011;25(8):814-30. doi: 10.1101/gad.2000211.
83. Ura S, Masuyama N, Graves JD, Gotoh Y. MST1-JNK promotes apoptosis via caspase-dependent and independent pathways. Genes Cells. 2001;6(6):519-30.
84. Ura S, Nishina H, Gotoh Y, Katada T. Activation of the c-Jun N-terminal kinase pathway by MST1 is essential and sufficient for the induction of chromatin condensation during apoptosis. Mol Cell Biol. 2007;27(15):5514-22. doi: 10.1128/MCB.00199-07.
85. Varelas X, Wrana JL. Coordinating developmental signaling: novel roles for the Hippo pathway. Trends Cell Biol. 2012;22(2):88-96. doi: 10.1016/j.tcb.2011.10.002.
86. Varelas X, Sakuma R, Samavarchi-Tehrani P, Peerani R, Rao BM, Dembowy J, et al. TAZ controls Smad nucleocytoplasmic shuttling and regulates human embryonic stem-cell self-renewal. Nat Cell Biol. 2008;10(7):837-48. doi: 10.1038/ncb1748.
87. Varelas X, Miller BW, Sopko R, Song S, Gregorieff A, Fellouse FA, et al. The Hippo pathway regulates Wnt/beta-catenin signaling. Dev Cell. 2010a;18(4):579-91. doi: 10.1016/j.devcel.2010.03.007.
88. Varelas X, Samavarchi-Tehrani P, Narimatsu M, Weiss A, Cockburn K, Larsen BG, et al. The Crumbs complex couples cell density sensing to Hippo-dependent control of the TGF-beta-SMAD pathway. Dev Cell. 2010b;19(6):831-44. doi: 10.1016/j.devcel.2010.11.012.
89. Vigneron AM, Ludwig RL, Vousden KH. Cytoplasmic ASPP1 inhibits apoptosis through the control of YAP. Genes Dev. 2010;24(21):2430-9. doi: 10.1101/gad.1954310.
90. Wang C, An J, Zhang P, Xu C, Gao K, Wu D, et al. The Nedd4-like ubiquitin E3 ligases target angiomotin/p130 to ubiquitin-dependent degradation. Biochem J. 2012;444(2):279-89. doi: 10.1042/BJ20111983.
91. Wells CD, Fawcett JP, Traweger A, Yamanaka Y, Goudreault M, Elder K, et al. A Rich1/Amot complex regulates the Cdc42 GTPase and apical-polarity proteins in epithelial cells. Cell. 2006;125(3):535-48. doi: 10.1016/j.cell.2006.02.045.
92. Wen W, Zhu F, Zhang J, Keum YS, Zykova T, Yao K, et al. MST1 promotes apoptosis through phosphorylation of histone H2AX. J Biol Chem. 2010;285(50):39108-16. doi: 10.1074/jbc.M110.151753.
93. Wu MY, Hill CS. Tgf-beta superfamily signaling in embryonic development and homeostasis. Dev Cell. 2009;16(3):329-43. doi: 10.1016/j.devcel.2009.02.012.
94. Xiao L, Chen Y, Ji M, Dong J. KIBRA regulates Hippo signaling activity via interactions with large tumor suppressor kinases. J Biol Chem. 2011;286(10):7788-96. doi: 10.1074/jbc.M110.173468.
95. Yabuta N, Mukai S, Okada N, Aylon Y, Nojima H. The tumor suppressor Lats2 is pivotal in Aurora A and Aurora B signaling during mitosis. Cell Cycle. 2011;10(16):2724-36.
96. Yang X, Yu K, Hao Y, Li DM, Stewart R, Insogna KL, et al. LATS1 tumour suppressor affects cytokinesis by inhibiting LIMK1. Nat Cell Biol. 2004;6(7):609-17. doi: 10.1038/ncb1140.
97. Yi C, Troutman S, Fera D, Stemmer-Rachamimov A, Avila JL, Christian N, et al. A tight junctionassociated Merlin-angiomotin complex mediates Merlin's regulation of mitogenic signaling and tumor suppressive functions. Cancer Cell. 2011;19(4):527-40. doi: 10.1016/j.ccr.2011.02.017.
98. Yim H, Sung CK, You J, Tian Y, Benjamin T. Nek1 and TAZ interact to maintain normal levels of polycystin 2. J Am Soc Nephrol. 2011;22(5):832-7. doi: 10.1681/ASN.2010090992.
99. Yoshihama Y, Sasaki K, Horikoshi Y, Suzuki A, Ohtsuka T, Hakuno F, et al. KIBRA suppresses apical exocytosis through inhibition of aPKC kinase activity in epithelial cells. Curr Biol. 2011;21(8):705-11. doi: 10.1016/j.cub.2011.03.029.
100. Yu J, Poulton J, Huang YC, Deng WM. The hippo pathway promotes Notch signaling in regulation of cell differentiation, proliferation, and oocyte polarity. PLoS One. 2008;3(3):e1761. doi: 10.1371/journal.pone.0001761.
101. Yu J, Zheng Y, Dong J, Klusza S, Deng WM, Pan D. Kibra functions as a tumor suppressor protein that regulates Hippo signaling in conjunction with Merlin and Expanded. Dev Cell. 2010;18(2):288-99. doi: 10.1016/j.devcel.2009.12.012.
102. Yuan F, Xie Q, Wu J, Bai Y, Mao B, Dong Y, et al. MST1 promotes apoptosis through regulating Sirt1-dependent p53 deacetylation. J Biol Chem. 2011;286(9):6940-5. doi: 10.1074/jbc.M110.182543.
103. Zhang N, Bai H, David KK, Dong J, Zheng Y, Cai J, et al. The Merlin/NF2 tumor suppressor functions through the YAP oncoprotein to regulate tissue homeostasis in mammals. Dev Cell. 2010;19(1):27-38. doi: 10.1016/j.devcel.2010.06.015.
104. Zhao B, Li L, Lu Q, Wang LH, Liu CY, Lei Q, et al. Angiomotin is a novel Hippo pathway component that inhibits YAP oncoprotein. Genes Dev. 2011a;25(1):51-63. doi: 10.1101/gad.2000111.
105. Zhao B, Tumaneng K, Guan KL. The Hippo pathway in organ size control, tissue regeneration and stem cell self-renewal. Nat Cell Biol. 2011b;13(8):877-83. doi: 10.1038/ncb2303.
106. Zhi X, Zhao D, Zhou Z, Liu R, Chen C. YAP promotes breast cell proliferation and survival partially through stabilizing the KLF5 transcription factor. Am J Pathol. 2012;180(6):2452-61. doi: 10.1016/j.ajpath.2012.02.025.
107. Zhou L, Hanemann CO. Merlin, a multi-suppressor from cell membrane to the nucleus. FEBS Lett. 2012;586(10):1403-8. doi: 10.1016/j.febslet.2012.03.016.
108. Zhou D, Zhang Y, Wu H, Barry E, Yin Y, Lawrence E, et al. Mst1 and Mst2 protein kinases restrain intestinal stem cell proliferation and colonic tumorigenesis by inhibition of Yes-associated protein (Yap) overabundance. Proc Natl Acad Sci U S A. 2011;108(49):E1312-20. doi: 10.1073/pnas.1110428108.