1932
0
  1. Home
  2. A-Z Publications
  3. Annual Review of Biochemistry
  4. Volume 88, 2019
  5. Article

Annual Review of Biochemistry

Volume 88, 2019

The Hippo Pathway: Biology and Pathophysiology

Abstract

The Hippo pathway was initially discovered in as a key regulator of tissue growth. It is an evolutionarily conserved signaling cascade regulating numerous biological processes, including cell growth and fate decision, organ size control, and regeneration. The core of the Hippo pathway in mammals consists of a kinase cascade, MST1/2 and LATS1/2, as well as downstream effectors, transcriptional coactivators YAP and TAZ. These core components of the Hippo pathway control transcriptional programs involved in cell proliferation, survival, mobility, stemness, and differentiation. The Hippo pathway is tightly regulated by both intrinsic and extrinsic signals, such as mechanical force, cell–cell contact, polarity, energy status, stress, and many diffusible hormonal factors, the majority of which act through G protein–coupled receptors. Here, we review the current understanding of molecular mechanisms by which signals regulate the Hippo pathway with an emphasis on mechanotransduction and the effects of this pathway on basic biology and human diseases.

Keyword(s): cancer, Hippo, LATS, mechanotransduction, phosphorylation, signal transduction, TAZ, YAP
Loading

Article metrics loading...

/content/journals/10.1146/annurev-biochem-013118-111829
2019-06-20
2024-04-19
Loading full text...

Full text loading...

/deliver/fulltext/biochem/88/1/annurev-biochem-013118-111829.html?itemId=/content/journals/10.1146/annurev-biochem-013118-111829&mimeType=html&fmt=ahah

Literature Cited

  1. 1. 
    Pan D. 2010. The hippo signaling pathway in development and cancer. Dev. Cell 19:491–505
     [Google Scholar]
  2. 2. 
    Yu FX, Zhao B, Guan KL 2015. Hippo pathway in organ size control, tissue homeostasis, and cancer. Cell 163:811–28
     [Google Scholar]
  3. 3. 
    Huang J, Wu S, Barrera J, Matthews K, Pan D 2005. The Hippo signaling pathway coordinately regulates cell proliferation and apoptosis by inactivating Yorkie, the Drosophila homolog of YAP. Cell 122:421–34
     [Google Scholar]
  4. 4. 
    Praskova M, Xia F, Avruch J 2008. MOBKL1A/MOBKL1B phosphorylation by MST1 and MST2 inhibits cell proliferation. Curr. Biol. 18:311–21
     [Google Scholar]
  5. 5. 
    Hergovich A, Schmitz D, Hemmings BA 2006. The human tumour suppressor LATS1 is activated by human MOB1 at the membrane. Biochem. Biophys. Res. Commun. 345:50–58
     [Google Scholar]
  6. 6. 
    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 24:2076–86
     [Google Scholar]
  7. 7. 
    Zhao B, Wei X, Li W, Udan RS, Yang Q et al. 2007. Inactivation of YAP oncoprotein by the Hippo pathway is involved in cell contact inhibition and tissue growth control. Genes Dev 21:2747–61
     [Google Scholar]
  8. 8. 
    Zhao B, Li L, Tumaneng K, Wang CY, Guan KL 2010. A coordinated phosphorylation by Lats and CK1 regulates YAP stability through SCFβ-TRCP. Genes Dev 24:72–85
     [Google Scholar]
  9. 9. 
    Liu CY, Zha ZY, Zhou X, Zhang H, Huang W et al. 2010. The Hippo tumor pathway promotes TAZ degradation by phosphorylating a phosphodegron and recruiting the SCFβ-TrCP E3 ligase. J. Biol. Chem. 285:37159–69
     [Google Scholar]
  10. 10. 
    Li Q, Li S, Mana-Capelli S, Roth Flach RJ, Danai LV et al. 2014. The conserved misshapen-warts-Yorkie pathway acts in enteroblasts to regulate intestinal stem cells in Drosophila. Dev. . Cell 31:291–304
     [Google Scholar]
  11. 11. 
    Li S, Cho YS, Yue T, Ip YT, Jiang J 2015. Overlapping functions of the MAP4K family kinases Hppy and Msn in Hippo signaling. Cell Discov 1:15038
     [Google Scholar]
  12. 12. 
    Zheng Y, Wang W, Liu B, Deng H, Uster E, Pan D 2015. Identification of Happyhour/MAP4K as alternative Hpo/Mst-like kinases in the Hippo kinase cascade. Dev. Cell 34:642–55
     [Google Scholar]
  13. 13. 
    Meng Z, Moroishi T, Mottier-Pavie V, Plouffe SW, Hansen CG et al. 2015. MAP4K family kinases act in parallel to MST1/2 to activate LATS1/2 in the Hippo pathway. Nat. Commun. 6:8357
     [Google Scholar]
  14. 14. 
    Plouffe SW, Meng Z, Lin KC, Lin B, Hong AW et al. 2016. Characterization of Hippo pathway components by gene inactivation. Mol. Cell 64:993–1008
     [Google Scholar]
  15. 15. 
    Meng Z, Moroishi T, Guan KL 2016. Mechanisms of Hippo pathway regulation. Genes Dev 30:1–17
     [Google Scholar]
  16. 16. 
    Goulev Y, Fauny JD, Gonzalez-Marti B, Flagiello D, Silber J, Zider A 2008. SCALLOPED interacts with YORKIE, the nuclear effector of the Hippo tumor-suppressor pathway in Drosophila. Curr. . Biol 18:435–41
     [Google Scholar]
  17. 17. 
    Zhao B, Ye X, Yu J, Li L, Li W et al. 2008. TEAD mediates YAP-dependent gene induction and growth control. Genes Dev 22:1962–71
     [Google Scholar]
  18. 18. 
    Zhang H, Liu CY, Zha ZY, Zhao B, Yao J et al. 2009. TEAD transcription factors mediate the function of TAZ in cell growth and epithelial-mesenchymal transition. J. Biol. Chem. 284:13355–62
     [Google Scholar]
  19. 19. 
    Guo T, Lu Y, Li P, Yin MX, Lv D et al. 2013. A novel partner of Scalloped regulates Hippo signaling via antagonizing Scalloped-Yorkie activity. Cell Res 23:1201–14
     [Google Scholar]
  20. 20. 
    Koontz LM, Liu-Chittenden Y, Yin F, Zheng Y, Yu J et al. 2013. The Hippo effector Yorkie controls normal tissue growth by antagonizing scalloped-mediated default repression. Dev. Cell 25:388–401
     [Google Scholar]
  21. 21. 
    Ege N, Dowbaj AM, Jiang M, Howell M, Hooper S et al. 2018. Quantitative analysis reveals that actin and Src-family kinases regulate nuclear YAP1 and its export. Cell Syst 6:692–708.e13
     [Google Scholar]
  22. 22. 
    Manning SA, Dent LG, Kondo S, Zhao ZW, Plachta N, Harvey KF 2018. Dynamic fluctuations in subcellular localization of the Hippo pathway effector Yorkie in vivo. Curr. Biol. 28:1651–60.e4
     [Google Scholar]
  23. 23. 
    Elosegui-Artola A, Andreu I, Beedle AEM, Lezamiz A, Uroz M et al. 2017. Force triggers YAP nuclear entry by regulating transport across nuclear pores. Cell 171:1397–410.e14
     [Google Scholar]
  24. 24. 
    Dong J, Feldmann G, Huang J, Wu S, Zhang N et al. 2007. Elucidation of a universal size-control mechanism in Drosophila and mammals. Cell 130:1120–33
     [Google Scholar]
  25. 25. 
    Zhang N, Bai H, David KK, Dong J, Zheng Y et al. 2010. The Merlin/NF2 tumor suppressor functions through the YAP oncoprotein to regulate tissue homeostasis in mammals. Dev. Cell 19:27–38
     [Google Scholar]
  26. 26. 
    Zhou D, Zhang Y, Wu H, Barry E, Yin Y et al. 2011. Mst1 and Mst2 protein kinases restrain intestinal stem cell proliferation and colonic tumorigenesis by inhibition of Yes-associated protein (Yap) overabundance. PNAS 108:E1312–20
     [Google Scholar]
  27. 27. 
    Schlegelmilch K, Mohseni M, Kirak O, Pruszak J, Rodriguez JR et al. 2011. Yap1 acts downstream of α-catenin to control epidermal proliferation. Cell 144:782–95
     [Google Scholar]
  28. 28. 
    Ota M, Sasaki H. 2008. Mammalian Tead proteins regulate cell proliferation and contact inhibition as transcriptional mediators of Hippo signaling. Development 135:4059–69
     [Google Scholar]
  29. 29. 
    Qi Y, Yu J, Han W, Fan X, Qian H et al. 2016. A splicing isoform of TEAD4 attenuates the Hippo–YAP signalling to inhibit tumour proliferation. Nat. Commun. 7:ncomms11840
     [Google Scholar]
  30. 30. 
    Zanconato F, Forcato M, Battilana G, Azzolin L, Quaranta E et al. 2015. Genome-wide association between YAP/TAZ/TEAD and AP-1 at enhancers drives oncogenic growth. Nat. Cell Biol. 17:1218–27
     [Google Scholar]
  31. 31. 
    Stein C, Bardet AF, Roma G, Bergling S, Clay I et al. 2015. YAP1 exerts its transcriptional control via TEAD-mediated activation of enhancers. PLOS Genet 11:e1005465
     [Google Scholar]
  32. 32. 
    Galli GG, Carrara M, Yuan WC, Valdes-Quezada C, Gurung B et al. 2015. YAP drives growth by controlling transcriptional pause release from dynamic enhancers. Mol. Cell 60:328–37
     [Google Scholar]
  33. 33. 
    Lin KC, Moroishi T, Meng Z, Jeong HS, Plouffe SW et al. 2017. Regulation of Hippo pathway transcription factor TEAD by p38 MAPK-induced cytoplasmic translocation. Nat. Cell Biol. 19:996–1002
     [Google Scholar]
  34. 34. 
    Oh H, Slattery M, Ma L, Crofts A, White KP et al. 2013. Genome-wide association of Yorkie with chromatin and chromatin-remodeling complexes. Cell Rep 3:309–18
     [Google Scholar]
  35. 35. 
    Ikmi A, Gaertner B, Seidel C, Srivastava M, Zeitlinger J, Gibson MC 2014. Molecular evolution of the Yap/Yorkie proto-oncogene and elucidation of its core transcriptional program. Mol. Biol. Evol. 31:1375–90
     [Google Scholar]
  36. 36. 
    Cebola I, Rodriguez-Segui SA, Cho CH, Bessa J, Rovira M et al. 2015. TEAD and YAP regulate the enhancer network of human embryonic pancreatic progenitors. Nat. Cell Biol. 17:615–26
     [Google Scholar]
  37. 37. 
    Qing Y, Yin F, Wang W, Zheng Y, Guo P et al. 2014. The Hippo effector Yorkie activates transcription by interacting with a histone methyltransferase complex through Ncoa6. eLife 3:e02564
     [Google Scholar]
  38. 38. 
    Skibinski A, Breindel JL, Prat A, Galvan P, Smith E et al. 2014. The Hippo transducer TAZ interacts with the SWI/SNF complex to regulate breast epithelial lineage commitment. Cell Rep 6:1059–72
     [Google Scholar]
  39. 39. 
    Cabochette P, Vega-Lopez G, Bitard J, Parain K, Chemouny R et al. 2015. YAP controls retinal stem cell DNA replication timing and genomic stability. eLife 4:e08488
     [Google Scholar]
  40. 40. 
    Peng HW, Slattery M, Mann RS 2009. Transcription factor choice in the Hippo signaling pathway: homothorax and yorkie regulation of the microRNA bantam in the progenitor domain of the Drosophila eye imaginal disc. Genes Dev 23:2307–19
     [Google Scholar]
  41. 41. 
    Kuser-Abali G, Alptekin A, Lewis M, Garraway IP, Cinar B 2015. YAP1 and AR interactions contribute to the switch from androgen-dependent to castration-resistant growth in prostate cancer. Nat. Commun. 6:8126
     [Google Scholar]
  42. 42. 
    Liu H, Dai X, Cao X, Yan H, Ji X et al. 2018. PRDM4 mediates YAP-induced cell invasion by activating leukocyte-specific integrin β2 expression. EMBO Rep 19:e45180
     [Google Scholar]
  43. 43. 
    Halder G, Polaczyk P, Kraus ME, Hudson A, Kim J et al. 1998. The Vestigial and Scalloped proteins act together to directly regulate wing-specific gene expression in Drosophila. . Genes Dev 12:3900–9
     [Google Scholar]
  44. 44. 
    Simmonds AJ, Liu X, Soanes KH, Krause HM, Irvine KD, Bell JB 1998. Molecular interactions between Vestigial and Scalloped promote wing formation in Drosophila. . Genes Dev 12:3815–20
     [Google Scholar]
  45. 45. 
    Jiao S, Wang H, Shi Z, Dong A, Zhang W et al. 2014. A peptide mimicking VGLL4 function acts as a YAP antagonist therapy against gastric cancer. Cancer Cell 25:166–80
     [Google Scholar]
  46. 46. 
    Lin Z, Guo H, Cao Y, Zohrabian S, Zhou P et al. 2016. Acetylation of VGLL4 regulates Hippo-YAP signaling and postnatal cardiac growth. Dev. Cell 39:466–79
     [Google Scholar]
  47. 47. 
    Zhang P, Pei C, Wang X, Xiang J, Sun BF et al. 2017. A balance of Yki/Sd activator and E2F1/Sd repressor complexes controls cell survival and affects organ size. Dev. Cell 43:603–17.e5
     [Google Scholar]
  48. 48. 
    Kapoor A, Yao W, Ying H, Hua S, Liewen A et al. 2014. Yap1 activation enables bypass of oncogenic Kras addiction in pancreatic cancer. Cell 158:185–97
     [Google Scholar]
  49. 49. 
    Cai WY, Lin LY, Hao H, Zhang SM, Ma F et al. 2017. Yes-associated protein/TEA domain family member and hepatocyte nuclear factor 4-α (HNF4α) repress reciprocally to regulate hepatocarcinogenesis in rats and mice. Hepatology 65:1206–21
     [Google Scholar]
  50. 50. 
    Kim M, Kim T, Johnson RL, Lim DS 2015. Transcriptional co-repressor function of the Hippo pathway transducers YAP and TAZ. Cell Rep 11:270–82
     [Google Scholar]
  51. 51. 
    Chen Q, Zhang N, Xie R, Wang W, Cai J et al. 2015. Homeostatic control of Hippo signaling activity revealed by an endogenous activating mutation in YAP. Genes Dev 29:1285–97
     [Google Scholar]
  52. 52. 
    Dai X, Liu H, Shen S, Guo X, Yan H et al. 2015. YAP activates the Hippo pathway in a negative feedback loop. Cell Res 25:1175–78
     [Google Scholar]
  53. 53. 
    Moroishi T, Park HW, Qin B, Chen Q, Meng Z et al. 2015. A YAP/TAZ-induced feedback mechanism regulates Hippo pathway homeostasis. Genes Dev 29:1271–84
     [Google Scholar]
  54. 54. 
    Furukawa KT, Yamashita K, Sakurai N, Ohno S 2017. The epithelial circumferential actin belt regulates YAP/TAZ through nucleocytoplasmic shuttling of Merlin. Cell Rep 20:1435–47
     [Google Scholar]
  55. 55. 
    Hong AW, Meng Z, Yuan HX, Plouffe SW, Moon S et al. 2017. Osmotic stress-induced phosphorylation by NLK at Ser128 activates YAP. EMBO Rep 18:72–86
     [Google Scholar]
  56. 56. 
    Moon S, Kim W, Kim S, Kim Y, Song Y et al. 2017. Phosphorylation by NLK inhibits YAP-14–3–3-interactions and induces its nuclear localization. EMBO Rep 18:61–71
     [Google Scholar]
  57. 57. 
    Zhao Y, Khanal P, Savage P, She YM, Cyr TD, Yang X 2014. YAP-induced resistance of cancer cells to antitubulin drugs is modulated by a Hippo-independent pathway. Cancer Res 74:4493–503
     [Google Scholar]
  58. 58. 
    Cho YS, Zhu J, Li S, Wang B, Han Y, Jiang J 2018. Regulation of Yki/Yap subcellular localization and Hpo signaling by a nuclear kinase PRP4K. Nat. Commun. 9:1657
     [Google Scholar]
  59. 59. 
    Bissell MJ, Aggeler J. 1987. Dynamic reciprocity: How do extracellular matrix and hormones direct gene expression. ? Prog. Clin. Biol. Res. 249:251–62
     [Google Scholar]
  60. 60. 
    Bissell MJ, Barcellos-Hoff MH. 1987. The influence of extracellular matrix on gene expression: Is structure the message?. J. Cell Sci. Suppl. 8:327–43
     [Google Scholar]
  61. 61. 
    Nishioka N, Inoue K, Adachi K, Kiyonari H, Ota M et al. 2009. The Hippo signaling pathway components Lats and Yap pattern Tead4 activity to distinguish mouse trophectoderm from inner cell mass. Dev. Cell 16:398–410
     [Google Scholar]
  62. 62. 
    Li Y, Zhou H, Li F, Chan SW, Lin Z et al. 2015. Angiomotin binding-induced activation of Merlin/NF2 in the Hippo pathway. Cell Res 25:801–17
     [Google Scholar]
  63. 63. 
    Kim NG, Koh E, Chen X, Gumbiner BM 2011. E-cadherin mediates contact inhibition of proliferation through Hippo signaling-pathway components. PNAS 108:11930–35
     [Google Scholar]
  64. 64. 
    Aragona M, Panciera T, Manfrin A, Giulitti S, Michielin F et al. 2013. A mechanical checkpoint controls multicellular growth through YAP/TAZ regulation by actin-processing factors. Cell 154:1047–59
     [Google Scholar]
  65. 65. 
    Wada K, Itoga K, Okano T, Yonemura S, Sasaki H 2011. Hippo pathway regulation by cell morphology and stress fibers. Development 138:3907–14
     [Google Scholar]
  66. 66. 
    Dupont S, Morsut L, Aragona M, Enzo E, Giulitti S et al. 2011. Role of YAP/TAZ in mechanotransduction. Nature 474:179–83
     [Google Scholar]
  67. 67. 
    Calvo F, Ege N, Grande-Garcia A, Hooper S, Jenkins RP et al. 2013. Mechanotransduction and YAP-dependent matrix remodelling is required for the generation and maintenance of cancer-associated fibroblasts. Nat. Cell Biol. 15:637–46
     [Google Scholar]
  68. 68. 
    Codelia VA, Sun G, Irvine KD 2014. Regulation of YAP by mechanical strain through Jnk and Hippo signaling. Curr. Biol. 24:2012–17
     [Google Scholar]
  69. 69. 
    Zhong W, Tian K, Zheng X, Li L, Zhang W et al. 2013. Mesenchymal stem cell and chondrocyte fates in a multishear microdevice are regulated by Yes-associated protein. Stem Cells Dev 22:2083–93
     [Google Scholar]
  70. 70. 
    Wang KC, Yeh YT, Nguyen P, Limqueco E, Lopez J et al. 2016. Flow-dependent YAP/TAZ activities regulate endothelial phenotypes and atherosclerosis. PNAS 113:11525–30
     [Google Scholar]
  71. 71. 
    Wang L, Luo JY, Li B, Tian XY, Chen LJ et al. 2016. Integrin-YAP/TAZ-JNK cascade mediates atheroprotective effect of unidirectional shear flow. Nature 540:579–82
     [Google Scholar]
  72. 72. 
    Nakajima H, Yamamoto K, Agarwala S, Terai K, Fukui H et al. 2017. Flow-dependent endothelial YAP regulation contributes to vessel maintenance. Dev. Cell 40:523–36.e6
     [Google Scholar]
  73. 73. 
    Lee HJ, Diaz MF, Price KM, Ozuna JA, Zhang S et al. 2017. Fluid shear stress activates YAP1 to promote cancer cell motility. Nat. Commun. 8:14122
     [Google Scholar]
  74. 74. 
    Lee HJ, Ewere A, Diaz MF, Wenzel PL 2018. TAZ responds to fluid shear stress to regulate the cell cycle. Cell Cycle 17:147–53
     [Google Scholar]
  75. 75. 
    Babic AM, Chen CC, Lau LF 1999. Fisp12/mouse connective tissue growth factor mediates endothelial cell adhesion and migration through integrin αvβ3, promotes endothelial cell survival, and induces angiogenesis in vivo. Mol. Cell. Biol. 19:2958–66
     [Google Scholar]
  76. 76. 
    Jedsadayanmata A, Chen CC, Kireeva ML, Lau LF, Lam SC 1999. Activation-dependent adhesion of human platelets to Cyr61 and Fisp12/mouse connective tissue growth factor is mediated through integrin αIIbβ3. J. Biol. Chem. 274:24321–27
     [Google Scholar]
  77. 77. 
    Porazinski S, Wang H, Asaoka Y, Behrndt M, Miyamoto T et al. 2015. YAP is essential for tissue tension to ensure vertebrate 3D body shape. Nature 521:217–21
     [Google Scholar]
  78. 78. 
    Bertero T, Cottrill KA, Lu Y, Haeger CM, Dieffenbach P et al. 2015. Matrix remodeling promotes pulmonary hypertension through feedback mechanoactivation of the YAP/TAZ-miR-130/301 circuit. Cell Rep 13:1016–32
     [Google Scholar]
  79. 79. 
    Bertero T, Oldham WM, Cottrill KA, Pisano S, Vanderpool RR et al. 2016. Vascular stiffness mechanoactivates YAP/TAZ-dependent glutaminolysis to drive pulmonary hypertension. J. Clin. Invest. 126:3313–35
     [Google Scholar]
  80. 80. 
    Benham-Pyle BW, Pruitt BL, Nelson WJ 2015. Cell adhesion. Mechanical strain induces E-cadherin-dependent Yap1 and β-catenin activation to drive cell cycle entry. Science 348:1024–27
     [Google Scholar]
  81. 81. 
    Foster CT, Gualdrini F, Treisman R 2017. Mutual dependence of the MRTF–SRF and YAP–TEAD pathways in cancer-associated fibroblasts is indirect and mediated by cytoskeletal dynamics. Genes Dev 31:2361–75
     [Google Scholar]
  82. 82. 
    Meng Z, Qiu Y, Lin KC, Kumar A, Placone JK et al. 2018. RAP2 mediates mechanoresponses of the Hippo pathway. Nature 560:655–60
     [Google Scholar]
  83. 83. 
    Hu JK, Du W, Shelton SJ, Oldham MC, DiPersio CM, Klein OD 2017. An FAK-YAP-mTOR signaling axis regulates stem cell-based tissue renewal in mice. Cell Stem Cell 21:91–106.e6
     [Google Scholar]
  84. 84. 
    Humphrey JD, Dufresne ER, Schwartz MA 2014. Mechanotransduction and extracellular matrix homeostasis. Nat. Rev. Mol. Cell Biol. 15:802–12
     [Google Scholar]
  85. 85. 
    Kim NG, Gumbiner BM. 2015. Adhesion to fibronectin regulates Hippo signaling via the FAK-Src-PI3K pathway. J. Cell Biol. 210:503–15
     [Google Scholar]
  86. 86. 
    Lachowski D, Cortes E, Robinson B, Rice A, Rombouts K, Del Rio Hernandez AE 2018. FAK controls the mechanical activation of YAP, a transcriptional regulator required for durotaxis. FASEB J 32:1099–107
     [Google Scholar]
  87. 87. 
    Yeh YC, Ling JY, Chen WC, Lin HH, Tang MJ 2017. Mechanotransduction of matrix stiffness in regulation of focal adhesion size and number: reciprocal regulation of caveolin-1 and β1 integrin. Sci. Rep. 7:15008
     [Google Scholar]
  88. 88. 
    Elbediwy A, Vincent-Mistiaen ZI, Spencer-Dene B, Stone RK, Boeing S et al. 2016. Integrin signalling regulates YAP and TAZ to control skin homeostasis. Development 143:1674–87
     [Google Scholar]
  89. 89. 
    Zhao B, Li L, Wang L, Wang CY, Yu J, Guan KL 2012. Cell detachment activates the Hippo pathway via cytoskeleton reorganization to induce anoikis. Genes Dev 26:54–68
     [Google Scholar]
  90. 90. 
    Driscoll TP, Cosgrove BD, Heo SJ, Shurden ZE, Mauck RL 2015. Cytoskeletal to nuclear strain transfer regulates YAP signaling in mesenchymal stem cells. Biophys. J. 108:2783–93
     [Google Scholar]
  91. 91. 
    Fletcher GC, Elbediwy A, Khanal I, Ribeiro PS, Tapon N, Thompson BJ 2015. The Spectrin cytoskeleton regulates the Hippo signalling pathway. EMBO J 34:940–54
     [Google Scholar]
  92. 92. 
    Deng H, Wang W, Yu J, Zheng Y, Qing Y, Pan D 2015. Spectrin regulates Hippo signaling by modulating cortical actomyosin activity. eLife 4:e06567
     [Google Scholar]
  93. 93. 
    Yu FX, Zhao B, Panupinthu N, Jewell JL, Lian I et al. 2012. Regulation of the Hippo-YAP pathway by G-protein-coupled receptor signaling. Cell 150:780–91
     [Google Scholar]
  94. 94. 
    Fletcher GC, Diaz-de-la-Loza MD, Borreguero-Munoz N, Holder M, Aguilar-Aragon M, Thompson BJ 2018. Mechanical strain regulates the Hippo pathway in Drosophila. . Development 145:dev159467
     [Google Scholar]
  95. 95. 
    Li Q, Nirala NK, Nie Y, Chen HJ, Ostroff G et al. 2018. Ingestion of food particles regulates the mechanosensing Misshapen-Yorkie pathway in Drosophila intestinal growth. Dev. Cell 45:433–49.e6
     [Google Scholar]
  96. 96. 
    Gloerich M, ten Klooster JP, Vliem MJ, Koorman T, Zwartkruis FJ et al. 2012. Rap2A links intestinal cell polarity to brush border formation. Nat. Cell Biol. 14:793–801
     [Google Scholar]
  97. 97. 
    Kolesnikov YS, Nokhrina KP, Kretynin SV, Volotovski ID, Martinec J et al. 2012. Molecular structure of phospholipase D and regulatory mechanisms of its activity in plant and animal cells. Biochemistry 77:1–14
     [Google Scholar]
  98. 98. 
    Vitorino P, Yeung S, Crow A, Bakke J, Smyczek T et al. 2015. MAP4K4 regulates integrin-FERM binding to control endothelial cell motility. Nature 519:425–30
     [Google Scholar]
  99. 99. 
    Yue J, Xie M, Gou X, Lee P, Schneider MD, Wu X 2014. Microtubules regulate focal adhesion dynamics through MAP4K4. Dev. Cell 31:572–85
     [Google Scholar]
  100. 100. 
    Pannekoek WJ, Linnemann JR, Brouwer PM, Bos JL, Rehmann H 2013. Rap1 and Rap2 antagonistically control endothelial barrier resistance. PLOS ONE 8:e57903
     [Google Scholar]
  101. 101. 
    Freeman SA, Christian S, Austin P, Iu I, Graves ML et al. 2017. Applied stretch initiates directional invasion through the action of Rap1 GTPase as a tension sensor. J. Cell Sci. 130:152–63
     [Google Scholar]
  102. 102. 
    Chang YC, Wu JW, Hsieh YC, Huang TH, Liao ZM et al. 2018. Rap1 negatively regulates the hippo pathway to polarize directional protrusions in collective cell migration. Cell Rep 22:2160–75
     [Google Scholar]
  103. 103. 
    O'Keefe DD, Gonzalez-Nino E, Burnett M, Dylla L, Lambeth SM et al. 2009. Rap1 maintains adhesion between cells to affect Egfr signaling and planar cell polarity in Drosophila. . Dev. Biol 333:143–60
     [Google Scholar]
  104. 104. 
    Treisman JE, Ito N, Rubin GM 1997. misshapen encodes a protein kinase involved in cell shape control in Drosophila. . Gene 186:119–25
     [Google Scholar]
  105. 105. 
    Liu T, Rohn JL, Picone R, Kunda P, Baum B 2010. Tao-1 is a negative regulator of microtubule plus-end growth. J. Cell Sci. 123:2708–16
     [Google Scholar]
  106. 106. 
    Boettner B, Van Aelst L 2007. The Rap GTPase activator Drosophila PDZ-GEF regulates cell shape in epithelial migration and morphogenesis. Mol. Cell. Biol. 27:7966–80
     [Google Scholar]
  107. 107. 
    Rodriguez-Boulan E, Macara IG. 2014. Organization and execution of the epithelial polarity programme. Nat. Rev. Mol. Cell Biol. 15:225–42
     [Google Scholar]
  108. 108. 
    Chen SN, Gurha P, Lombardi R, Ruggiero A, Willerson JT, Marian AJ 2014. The Hippo pathway is activated and is a causal mechanism for adipogenesis in arrhythmogenic cardiomyopathy. Circ. Res. 114:454–68
     [Google Scholar]
  109. 109. 
    Genevet A, Wehr MC, Brain R, Thompson BJ, Tapon N 2010. Kibra is a regulator of the Salvador/Warts/Hippo signaling network. Dev. Cell 18:300–8
     [Google Scholar]
  110. 110. 
    Yu J, Zheng Y, Dong J, Klusza S, Deng WM, Pan D 2010. Kibra functions as a tumor suppressor protein that regulates Hippo signaling in conjunction with Merlin and Expanded. Dev. Cell 18:288–99
     [Google Scholar]
  111. 111. 
    Yin F, Yu J, Zheng Y, Chen Q, Zhang N, Pan D 2013. Spatial organization of Hippo signaling at the plasma membrane mediated by the tumor suppressor Merlin/NF2. Cell 154:1342–55
     [Google Scholar]
  112. 112. 
    Skouloudaki K, Puetz M, Simons M, Courbard JR, Boehlke C et al. 2009. Scribble participates in Hippo signaling and is required for normal zebrafish pronephros development. PNAS 106:8579–84
     [Google Scholar]
  113. 113. 
    Yang CC, Graves HK, Moya IM, Tao C, Hamaratoglu F et al. 2015. Differential regulation of the Hippo pathway by adherens junctions and apical-basal cell polarity modules. PNAS 112:1785–90
     [Google Scholar]
  114. 114. 
    Liu J, Li J, Li P, Wang Y, Liang Z et al. 2017. Loss of DLG5 promotes breast cancer malignancy by inhibiting the Hippo signaling pathway. Sci. Rep. 7:42125
     [Google Scholar]
  115. 115. 
    Szymaniak AD, Mahoney JE, Cardoso WV, Varelas X 2015. Crumbs3-mediated polarity directs airway epithelial cell fate through the Hippo pathway effector Yap. Dev. Cell 34:283–96
     [Google Scholar]
  116. 116. 
    Huang JM, Nagatomo I, Suzuki E, Mizuno T, Kumagai T et al. 2013. YAP modifies cancer cell sensitivity to EGFR and survivin inhibitors and is negatively regulated by the non-receptor type protein tyrosine phosphatase 14. Oncogene 32:2220–29
     [Google Scholar]
  117. 117. 
    Wang W, Huang J, Wang X, Yuan J, Li X et al. 2012. PTPN14 is required for the density-dependent control of YAP1. Genes Dev 26:1959–71
     [Google Scholar]
  118. 118. 
    Liu X, Yang N, Figel SA, Wilson KE, Morrison CD et al. 2013. PTPN14 interacts with and negatively regulates the oncogenic function of YAP. Oncogene 32:1266–73
     [Google Scholar]
  119. 119. 
    Bossuyt W, Chen CL, Chen Q, Sudol M, McNeill H et al. 2014. An evolutionary shift in the regulation of the Hippo pathway between mice and flies. Oncogene 33:1218–28
     [Google Scholar]
  120. 120. 
    Martin D, Degese MS, Vitale-Cross L, Iglesias-Bartolome R, Valera JLC et al. 2018. Assembly and activation of the Hippo signalome by FAT1 tumor suppressor. Nat. Commun. 9:2372
     [Google Scholar]
  121. 121. 
    Ragni CV, Diguet N, Le Garrec JF, Novotova M, Resende TP et al. 2017. Amotl1 mediates sequestration of the Hippo effector Yap1 downstream of Fat4 to restrict heart growth. Nat. Commun. 8:14582
     [Google Scholar]
  122. 122. 
    Miller E, Yang J, DeRan M, Wu C, Su AI et al. 2012. Identification of serum-derived sphingosine-1-phosphate as a small molecule regulator of YAP. Chem. Biol. 19:955–62
     [Google Scholar]
  123. 123. 
    Mo JS, Yu FX, Gong R, Brown JH, Guan KL 2012. Regulation of the Hippo-YAP pathway by protease-activated receptors (PARs). Genes Dev 26:2138–43
     [Google Scholar]
  124. 124. 
    Zhou X, Wang S, Wang Z, Feng X, Liu P et al. 2015. Estrogen regulates Hippo signaling via GPER in breast cancer. J. Clin. Invest. 125:2123–35
     [Google Scholar]
  125. 125. 
    Yu FX, Luo J, Mo JS, Liu G, Kim YC et al. 2014. Mutant Gq/11 promote uveal melanoma tumorigenesis by activating YAP. Cancer Cell 25:822–30
     [Google Scholar]
  126. 126. 
    Azad T, Janse van Rensburg HJ, Lightbody ED, Neveu B, Champagne A et al. 2018. A LATS biosensor screen identifies VEGFR as a regulator of the Hippo pathway in angiogenesis. Nat. Commun. 9:1061
     [Google Scholar]
  127. 127. 
    Wang X, Freire Valls A, Schermann G, Shen Y, Moya IM et al. 2017. YAP/TAZ orchestrate VEGF signaling during developmental angiogenesis. Dev. Cell 42:462–78.e7
     [Google Scholar]
  128. 128. 
    Sorrentino G, Ruggeri N, Zannini A, Ingallina E, Bertolio R et al. 2017. Glucocorticoid receptor signalling activates YAP in breast cancer. Nat. Commun. 8:14073
     [Google Scholar]
  129. 129. 
    Miranda MZ, Bialik JF, Speight P, Dan Q, Yeung T et al. 2017. TGF-β1 regulates the expression and transcriptional activity of TAZ protein via a Smad3-independent, myocardin-related transcription factor-mediated mechanism. J. Biol. Chem. 292:14902–20
     [Google Scholar]
  130. 130. 
    Taniguchi K, Wu LW, Grivennikov SI, de Jong PR, Lian I et al. 2015. A gp130-Src-YAP module links inflammation to epithelial regeneration. Nature 519:57–62
     [Google Scholar]
  131. 131. 
    Sorrentino G, Ruggeri N, Specchia V, Cordenonsi M, Mano M et al. 2014. Metabolic control of YAP and TAZ by the mevalonate pathway. Nat. Cell Biol. 16:357–66
     [Google Scholar]
  132. 132. 
    Wang Z, Wu Y, Wang H, Zhang Y, Mei L et al. 2014. Interplay of mevalonate and Hippo pathways regulates RHAMM transcription via YAP to modulate breast cancer cell motility. PNAS 111:E89–98
     [Google Scholar]
  133. 133. 
    DeRan M, Yang J, Shen CH, Peters EC, Fitamant J et al. 2014. Energy stress regulates Hippo-YAP signaling involving AMPK-mediated regulation of angiomotin-like 1 protein. Cell Rep 9:495–503
     [Google Scholar]
  134. 134. 
    Gailite I, Aerne BL, Tapon N 2015. Differential control of Yorkie activity by LKB1/AMPK and the Hippo/Warts cascade in the central nervous system. PNAS 112:E5169–78
     [Google Scholar]
  135. 135. 
    Mo JS, Meng Z, Kim YC, Park HW, Hansen CG et al. 2015. Cellular energy stress induces AMPK-mediated regulation of YAP and the Hippo pathway. Nat. Cell Biol. 17:500–10
     [Google Scholar]
  136. 136. 
    Wang W, Xiao ZD, Li X, Aziz KE, Gan B et al. 2015. AMPK modulates Hippo pathway activity to regulate energy homeostasis. Nat. Cell Biol. 17:490–99
     [Google Scholar]
  137. 137. 
    Peng C, Zhu Y, Zhang W, Liao Q, Chen Y et al. 2017. Regulation of the Hippo-YAP pathway by glucose sensor O-GlcNAcylation. Mol. Cell 68:591–604.e5
     [Google Scholar]
  138. 138. 
    Zhang X, Qiao Y, Wu Q, Chen Y, Zou S et al. 2017. The essential role of YAP O-GlcNAcylation in high-glucose-stimulated liver tumorigenesis. Nat. Commun. 8:15280
     [Google Scholar]
  139. 139. 
    Liu Y, Lu Z, Shi Y, Sun F 2018. AMOT is required for YAP function in high glucose induced liver malignancy. Biochem. Biophys. Res. Commun. 495:1555–61
     [Google Scholar]
  140. 140. 
    Ma B, Chen Y, Chen L, Cheng H, Mu C et al. 2015. Hypoxia regulates Hippo signalling through the SIAH2 ubiquitin E3 ligase. Nat. Cell Biol. 17:95–103
     [Google Scholar]
  141. 141. 
    Wu H, Wei L, Fan F, Ji S, Zhang S et al. 2015. Integration of Hippo signalling and the unfolded protein response to restrain liver overgrowth and tumorigenesis. Nat. Commun. 6:6239
     [Google Scholar]
  142. 142. 
    Ganem NJ, Cornils H, Chiu SY, O'Rourke KP, Arnaud J et al. 2014. Cytokinesis failure triggers Hippo tumor suppressor pathway activation. Cell 158:833–48
     [Google Scholar]
  143. 143. 
    Gerlach SU, Eichenlaub T, Herranz H 2018. Yorkie and JNK control tumorigenesis in Drosophila cells with cytokinesis failure. Cell Rep 23:1491–503
     [Google Scholar]
  144. 144. 
    Zhang S, Chen Q, Liu Q, Li Y, Sun X et al. 2017. Hippo signaling suppresses cell ploidy and tumorigenesis through Skp2. Cancer Cell 31:669–84.e7
     [Google Scholar]
  145. 145. 
    Praskova M, Khoklatchev A, Ortiz-Vega S, Avruch J 2004. Regulation of the MST1 kinase by autophosphorylation, by the growth inhibitory proteins, RASSF1 and NORE1, and by Ras. Biochem. J. 381:453–62
     [Google Scholar]
  146. 146. 
    Glantschnig H, Rodan GA, Reszka AA 2002. Mapping of MST1 kinase sites of phosphorylation: activation and autophosphorylation. J. Biol. Chem. 277:42987–96
     [Google Scholar]
  147. 147. 
    Dent LG, Poon CL, Zhang X, Degoutin JL, Tipping M et al. 2015. The GTPase regulatory proteins Pix and Git control tissue growth via the Hippo pathway. Curr. Biol. 25:124–30
     [Google Scholar]
  148. 148. 
    Wright JH, Wang X, Manning G, LaMere BJ, Le P et al. 2003. The STE20 kinase HGK is broadly expressed in human tumor cells and can modulate cellular transformation, invasion, and adhesion. Mol. Cell. Biol. 23:2068–82
     [Google Scholar]
  149. 149. 
    Boggiano JC, Vanderzalm PJ, Fehon RG 2011. Tao-1 phosphorylates Hippo/MST kinases to regulate the Hippo-Salvador-Warts tumor suppressor pathway. Dev. Cell 21:888–95
     [Google Scholar]
  150. 150. 
    Poon CL, Lin JI, Zhang X, Harvey KF 2011. The sterile 20-like kinase Tao-1 controls tissue growth by regulating the Salvador-Warts-Hippo pathway. Dev. Cell 21:896–906
     [Google Scholar]
  151. 151. 
    Raman M, Earnest S, Zhang K, Zhao Y, Cobb MH 2007. TAO kinases mediate activation of p38 in response to DNA damage. EMBO J 26:2005–14
     [Google Scholar]
  152. 152. 
    Couzens AL, Knight JD, Kean MJ, Teo G, Weiss A et al. 2013. Protein interaction network of the mammalian Hippo pathway reveals mechanisms of kinase-phosphatase interactions. Sci. Signal. 6:rs15
     [Google Scholar]
  153. 153. 
    Guo C, Zhang X, Pfeifer GP 2011. The tumor suppressor RASSF1A prevents dephosphorylation of the mammalian STE20-like kinases MST1 and MST2. J. Biol. Chem. 286:6253–61
     [Google Scholar]
  154. 154. 
    Bae SJ, Ni L, Osinski A, Tomchick DR, Brautigam CA, Luo X 2017. SAV1 promotes Hippo kinase activation through antagonizing the PP2A phosphatase STRIPAK. eLife 6:e30278
     [Google Scholar]
  155. 155. 
    Zheng Y, Liu B, Wang L, Lei H, Pulgar Prieto KD, Pan D 2017. Homeostatic control of Hpo/MST kinase activity through autophosphorylation-dependent recruitment of the STRIPAK PP2A phosphatase complex. Cell Rep 21:3612–23
     [Google Scholar]
  156. 156. 
    Hwang J, Pallas DC. 2014. STRIPAK complexes: structure, biological function, and involvement in human diseases. Int. J. Biochem. Cell Biol. 47:118–48
     [Google Scholar]
  157. 157. 
    Khokhlatchev A, Rabizadeh S, Xavier R, Nedwidek M, Chen T et al. 2002. Identification of a novel Ras-regulated proapoptotic pathway. Curr. Biol. 12:253–65
     [Google Scholar]
  158. 158. 
    Sun S, Reddy BV, Irvine KD 2015. Localization of Hippo signalling complexes and Warts activation in vivo. Nat. Commun. 6:8402
     [Google Scholar]
  159. 159. 
    Si Y, Ji X, Cao X, Dai X, Xu L et al. 2017. Src inhibits the Hippo tumor suppressor pathway through tyrosine phosphorylation of Lats1. Cancer Res 77:4868–80
     [Google Scholar]
  160. 160. 
    Sanchez-Vega F, Mina M, Armenia J, Chatila WK, Luna A et al. 2018. Oncogenic signaling pathways in The Cancer Genome Atlas. Cell 173:321–37
     [Google Scholar]
  161. 161. 
    Zanconato F, Cordenonsi M, Piccolo S 2016. YAP/TAZ at the roots of cancer. Cancer Cell 29:783–803
     [Google Scholar]
  162. 162. 
    Tapon N, Harvey KF, Bell DW, Wahrer DC, Schiripo TA et al. 2002. salvador promotes both cell cycle exit and apoptosis in Drosophila and is mutated in human cancer cell lines. Cell 110:467–78
     [Google Scholar]
  163. 163. 
    Bai H, Gayyed MF, Lam-Himlin DM, Klein AP, Nayar SK et al. 2012. Expression of Yes-associated protein modulates Survivin expression in primary liver malignancies. Hum. Pathol. 43:1376–85
     [Google Scholar]
  164. 164. 
    Lin L, Sabnis AJ, Chan E, Olivas V, Cade L et al. 2015. The Hippo effector YAP promotes resistance to RAF- and MEK-targeted cancer therapies. Nat. Genet. 47:250–56
     [Google Scholar]
  165. 165. 
    Cottini F, Hideshima T, Xu C, Sattler M, Dori M et al. 2014. Rescue of Hippo coactivator YAP1 triggers DNA damage-induced apoptosis in hematological cancers. Nat. Med. 20:599–606
     [Google Scholar]
  166. 166. 
    Mohseni M, Sun J, Lau A, Curtis S, Goldsmith J et al. 2014. A genetic screen identifies an LKB1-MARK signalling axis controlling the Hippo-YAP pathway. Nat. Cell Biol. 16:108–17
     [Google Scholar]
  167. 167. 
    Gao Y, Zhang W, Han X, Li F, Wang X et al. 2014. YAP inhibits squamous transdifferentiation of Lkb1-deficient lung adenocarcinoma through ZEB2-dependent DNp63 repression. Nat. Commun. 5:4629
     [Google Scholar]
  168. 168. 
    Zheng X, Han H, Liu GP, Ma YX, Pan RL et al. 2017. lncRNA wires up Hippo and Hedgehog signaling to reprogramme glucose metabolism. EMBO J 36:3325–35
     [Google Scholar]
  169. 169. 
    Enzo E, Santinon G, Pocaterra A, Aragona M, Bresolin S et al. 2015. Aerobic glycolysis tunes YAP/TAZ transcriptional activity. EMBO J 34:1349–70
     [Google Scholar]
  170. 170. 
    Ohsawa S, Sato Y, Enomoto M, Nakamura M, Betsumiya A, Igaki T 2012. Mitochondrial defect drives non-autonomous tumour progression through Hippo signalling in Drosophila. . Nature 490:547–51
     [Google Scholar]
  171. 171. 
    Hu Y, Shin DJ, Pan H, Lin Z, Dreyfuss JM et al. 2017. YAP suppresses gluconeogenic gene expression through PGC1α. Hepatology 66:2029–41
     [Google Scholar]
  172. 172. 
    Santinon G, Brian I, Pocaterra A, Romani P, Franzolin E et al. 2018. dNTP metabolism links mechanical cues and YAP/TAZ to cell growth and oncogene-induced senescence. EMBO J 37:e97780
     [Google Scholar]
  173. 173. 
    Panciera T, Azzolin L, Fujimura A, Di Biagio D, Frasson C et al. 2016. Induction of expandable tissue-specific stem/progenitor cells through transient expression of YAP/TAZ. Cell Stem Cell 19:725–37
     [Google Scholar]
  174. 174. 
    Cordenonsi M, Zanconato F, Azzolin L, Forcato M, Rosato A et al. 2011. The Hippo transducer TAZ confers cancer stem cell-related traits on breast cancer cells. Cell 147:759–72
     [Google Scholar]
  175. 175. 
    Kim T, Yang SJ, Hwang D, Song J, Kim M et al. 2015. A basal-like breast cancer-specific role for SRF-IL6 in YAP-induced cancer stemness. Nat. Commun. 6:10186
     [Google Scholar]
  176. 176. 
    Basu-Roy U, Bayin NS, Rattanakorn K, Han E, Placantonakis DG et al. 2015. Sox2 antagonizes the Hippo pathway to maintain stemness in cancer cells. Nat. Commun. 6:6411
     [Google Scholar]
  177. 177. 
    Bora-Singhal N, Nguyen J, Schaal C, Perumal D, Singh S et al. 2015. YAP1 regulates OCT4 activity and SOX2 expression to facilitate self-renewal and vascular mimicry of stem-like cells. Stem Cells 33:1705–18
     [Google Scholar]
  178. 178. 
    Wang G, Lu X, Dey P, Deng P, Wu CC et al. 2016. Targeting YAP-dependent MDSC infiltration impairs tumor progression. Cancer Discov 6:80–95
     [Google Scholar]
  179. 179. 
    Guo X, Zhao Y, Yan H, Yang Y, Shen S et al. 2017. Single tumor-initiating cells evade immune clearance by recruiting type II macrophages. Genes Dev 31:247–59
     [Google Scholar]
  180. 180. 
    Janse van Rensburg HJ, Azad T, Ling M, Hao Y, Snetsinger B et al. 2018. The Hippo pathway component TAZ promotes immune evasion in human cancer through PD-L1. Cancer Res 78:1457–70
     [Google Scholar]
  181. 181. 
    Moroishi T, Hayashi T, Pan WW, Fujita Y, Holt MV et al. 2016. The Hippo pathway kinases LATS1/2 suppress cancer immunity. Cell 167:1525–39
     [Google Scholar]
  182. 182. 
    Katagiri K, Imamura M, Kinashi T 2006. Spatiotemporal regulation of the kinase Mst1 by binding protein RAPL is critical for lymphocyte polarity and adhesion. Nat. Immunol. 7:919–28
     [Google Scholar]
  183. 183. 
    Kurz AR, Pruenster M, Rohwedder I, Ramadass M, Schafer K et al. 2016. MST1-dependent vesicle trafficking regulates neutrophil transmigration through the vascular basement membrane. J. Clin. Invest. 126:4125–39
     [Google Scholar]
  184. 184. 
    Ueda Y, Katagiri K, Tomiyama T, Yasuda K, Habiro K et al. 2012. Mst1 regulates integrin-dependent thymocyte trafficking and antigen recognition in the thymus. Nat. Commun. 3:1098
     [Google Scholar]
  185. 185. 
    Du X, Wen J, Wang Y, Karmaus PWF, Khatamian A et al. 2018. Hippo/Mst signalling couples metabolic state and immune function of CD8α+ dendritic cells. Nature 558:141–45
     [Google Scholar]
  186. 186. 
    Liu B, Zheng Y, Yin F, Yu J, Silverman N, Pan D 2016. Toll receptor-mediated Hippo signaling controls innate immunity in Drosophila. . Cell 164:406–19
     [Google Scholar]
  187. 187. 
    Wang S, Xie F, Chu F, Zhang Z, Yang B et al. 2017. YAP antagonizes innate antiviral immunity and is targeted for lysosomal degradation through IKKε-mediated phosphorylation. Nat. Immunol. 18:733–43
     [Google Scholar]
  188. 188. 
    Zhang Q, Meng F, Chen S, Plouffe SW, Wu S et al. 2017. Hippo signalling governs cytosolic nucleic acid sensing through YAP/TAZ-mediated TBK1 blockade. Nat. Cell Biol. 19:362–74
     [Google Scholar]
  189. 189. 
    Geng J, Yu S, Zhao H, Sun X, Li X et al. 2017. The transcriptional coactivator TAZ regulates reciprocal differentiation of TH17 cells and Treg cells. Nat. Immunol. 18:800–12
     [Google Scholar]
  190. 190. 
    Heallen T, Zhang M, Wang J, Bonilla-Claudio M, Klysik E et al. 2011. Hippo pathway inhibits Wnt signaling to restrain cardiomyocyte proliferation and heart size. Science 332:458–61
     [Google Scholar]
  191. 191. 
    von Gise A, Lin Z, Schlegelmilch K, Honor LB, Pan GM et al. 2012. YAP1, the nuclear target of Hippo signaling, stimulates heart growth through cardiomyocyte proliferation but not hypertrophy. PNAS 109:2394–99
     [Google Scholar]
  192. 192. 
    Morikawa Y, Heallen T, Leach J, Xiao Y, Martin JF 2017. Dystrophin–glycoprotein complex sequesters Yap to inhibit cardiomyocyte proliferation. Nature 547:227–31
     [Google Scholar]
  193. 193. 
    Leach JP, Heallen T, Zhang M, Rahmani M, Morikawa Y et al. 2017. Hippo pathway deficiency reverses systolic heart failure after infarction. Nature 550:260–64
     [Google Scholar]
  194. 194. 
    Bassat E, Mutlak YE, Genzelinakh A, Shadrin IY, Baruch Umansky K et al. 2017. The extracellular matrix protein agrin promotes heart regeneration in mice. Nature 547:179–84
     [Google Scholar]
/content/journals/10.1146/annurev-biochem-013118-111829
Loading
The Hippo Pathway: Biology and Pathophysiology
Annual Review of Biochemistry 88, 577 (2019); https://doi.org/10.1146/annurev-biochem-013118-111829
/content/journals/10.1146/annurev-biochem-013118-111829
/content/journals/10.1146/annurev-biochem-013118-111829
Loading

Data & Media loading...

  • Article Type: Review Article

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error