Molecules and Cells

Korean Society for Molecular and Cellular Biology (한국분자세포생물학회)
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The TGFβ→TAK1→LATS→YAP1 Pathway Regulates the Spatiotemporal Dynamics of YAP1

  • Min-Kyu Kim (Department of Biochemistry, College of Medicine and Institute for Tumour Research, Chungbuk National University) ;
  • Sang-Hyun Han (Department of Biochemistry, College of Medicine and Institute for Tumour Research, Chungbuk National University) ;
  • Tae-Geun Park (Department of Biochemistry, College of Medicine and Institute for Tumour Research, Chungbuk National University) ;
  • Soo-Hyun Song (Department of Biochemistry, College of Medicine and Institute for Tumour Research, Chungbuk National University) ;
  • Ja-Youl Lee (Department of Biochemistry, College of Medicine and Institute for Tumour Research, Chungbuk National University) ;
  • You-Soub Lee (Department of Biochemistry, College of Medicine and Institute for Tumour Research, Chungbuk National University) ;
  • Seo-Yeong Yoo (Department of Biochemistry, College of Medicine and Institute for Tumour Research, Chungbuk National University) ;
  • Xin-Zi Chi (Department of Biochemistry, College of Medicine and Institute for Tumour Research, Chungbuk National University) ;
  • Eung-Gook Kim (Department of Biochemistry, College of Medicine and Medical Research Center, Chungbuk National University) ;
  • Ju-Won Jang (Department of Biomedical Science, Cheongju University) ;
  • Dae Sik Lim (Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST)) ;
  • Andre J. van Wijnen (Department of Biochemistry, University of Vermont) ;
  • Jung-Won Lee (Department of Biochemistry, College of Medicine and Institute for Tumour Research, Chungbuk National University) ;
  • Suk-Chul Bae (Department of Biochemistry, College of Medicine and Institute for Tumour Research, Chungbuk National University)
  • Received : 2023.05.25
  • Accepted : 2023.07.25
  • Published : 2023.10.31
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Abstract

The Hippo kinase cascade functions as a central hub that relays input from the "outside world" of the cell and translates it into specific cellular responses by regulating the activity of Yes-associated protein 1 (YAP1). How Hippo translates input from the extracellular signals into specific intracellular responses remains unclear. Here, we show that transforming growth factor β (TGFβ)-activated TAK1 activates LATS1/2, which then phosphorylates YAP1. Phosphorylated YAP1 (p-YAP1) associates with RUNX3, but not with TEAD4, to form a TGFβ-stimulated restriction (R)-point-associated complex which activates target chromatin loci in the nucleus. Soon after, p-YAP1 is exported to the cytoplasm. Attenuation of TGFβ signaling results in re-localization of unphosphorylated YAP1 to the nucleus, where it forms a YAP1/TEAD4/SMAD3/AP1/p300 complex. The TGFβ-stimulated spatiotemporal dynamics of YAP1 are abrogated in many cancer cells. These results identify a new pathway that integrates TGFβ signals and the Hippo pathway (TGFβ→TAK1→LATS1/2→YAP1 cascade) with a novel dynamic nuclear role for p-YAP1.

Keywords

Acknowledgement

S.-C.B. is supported by a Creative Research Grant (NRF-2014R1A3A2030690) through the National Research Foundation (NRF) of Korea. J.-W.L. is supported by Basic Science Research Program grant (NRF-2021R1I1A1A01060610) of Korea. M.-K.K. is supported by Basic Science Research Program grant (NRF-2017R1A6A3A11028050) of Korea. S.-H.S. is supported by Basic Science Research Program grant (NRF-2021R1I1A1A01059185). E.-G.K. is supported by Medical Research Center (MRC-2020R1A5A2017476) of Korea. D.-S. L. is supported by the National Creative Research Initiatives (NRF-2020-2079551) of Korea.

References

  1. Blagosklonny, M.V. and Pardee, A.B. (2002). The restriction point of the cell cycle. Cell Cycle 1, 103-110.  https://doi.org/10.4161/cc.1.2.108
  2. Bracken, A.P., Pasini, D., Capra, M., Prosperini, E., Colli, E., and Helin, K. (2003). EZH2 is downstream of the pRB-E2F pathway, essential for proliferation and amplified in cancer. EMBO J. 22, 5323-5335.  https://doi.org/10.1093/emboj/cdg542
  3. Bushnell, B. (2014). BBMap. Retrieved August 19, 2021, from https://sourceforge.net/projects/bbmap/ 
  4. Cao, R., Wang, L., Wang, H., Xia, L., Erdjument-Bromage, H., Tempst, P., Jones, R.S., and Zhang, Y. (2002). Role of histone H3 lysine 27 methylation in Polycomb-group silencing. Science 298, 1039-1043.  https://doi.org/10.1126/science.1076997
  5. Chang, L., Azzolin, L., Di Biagio, D., Zanconato, F., Battilana, G., Lucon Xiccato, R., Aragona, M., Giulitti, S., Panciera, T., Gandin, A., et al. (2018). The SWI/SNF complex is a mechanoregulated inhibitor of YAP and TAZ. Nature 563, 265-269.  https://doi.org/10.1038/s41586-018-0658-1
  6. Cheung, P.C., Campbell, D.G., Nebreda, A.R., and Cohen, P. (2003). Feedback control of the protein kinase TAK1 by SAPK2a/p38alpha. EMBO J. 22, 5793-5805.  https://doi.org/10.1093/emboj/cdg552
  7. Chi, X.Z., Lee, J.W., Lee, Y.S., Park, I.Y., Ito, Y., and Bae, S.C. (2017). Runx3 plays a critical role in restriction-point and defense against cellular transformation. Oncogene 36, 6884-6894.  https://doi.org/10.1038/onc.2017.290
  8. Chi, X.Z., Yang, J.O., Lee, K.Y., Ito, K., Sakakura, C., Li, Q.L., Kim, H.R., Cha, E.J., Lee, Y.H., Kaneda, A., et al. (2005). RUNX3 suppresses gastric epithelial cell growth by inducing p21(WAF1/Cip1) expression in cooperation with transforming growth factor {beta}-activated SMAD. Mol. Cell. Biol. 25, 8097-8107.  https://doi.org/10.1128/MCB.25.18.8097-8107.2005
  9. Cottini, F., Hideshima, T., Xu, C., Sattler, M., Dori, M., Agnelli, L., ten Hacken, E., Bertilaccio, M.T., Antonini, E., Neri, A., et al. (2014). Rescue of Hippo coactivator YAP1 triggers DNA damage-induced apoptosis in hematological cancers. Nat. Med. 20, 599-606.  https://doi.org/10.1038/nm.3562
  10. Deng, Y., Lu, J., Li, W., Wu, A., Zhang, X., Tong, W., Ho, K.K., Qin, L., Song, H., and Mak, K.K. (2018). Reciprocal inhibition of YAP/TAZ and NF-kappaB regulates osteoarthritic cartilage degradation. Nat. Commun. 9, 4564. 
  11. Denissova, N.G., Pouponnot, C., Long, J., He, D., and Liu, F. (2000). Transforming growth factor beta -inducible independent binding of SMAD to the Smad7 promoter. Proc. Natl. Acad. Sci. U. S. A. 97, 6397-6402.  https://doi.org/10.1073/pnas.090099297
  12. Dong, J., Feldmann, G., Huang, J., Wu, S., Zhang, N., Comerford, S.A., Gayyed, M.F., Anders, R.A., Maitra, A., and Pan, D. (2007). Elucidation of a universal size-control mechanism in Drosophila and mammals. Cell 130, 1120-1133.  https://doi.org/10.1016/j.cell.2007.07.019
  13. Fan, R., Kim, N.G., and Gumbiner, B.M. (2013). Regulation of Hippo pathway by mitogenic growth factors via phosphoinositide 3-kinase and phosphoinositide-dependent kinase-1. Proc. Natl. Acad. Sci. U. S. A. 110, 2569-2574.  https://doi.org/10.1073/pnas.1216462110
  14. Fujii, M., Toyoda, T., Nakanishi, H., Yatabe, Y., Sato, A., Matsudaira, Y., Ito, H., Murakami, H., Kondo, Y., Kondo, E., et al. (2012). TGF-beta synergizes with defects in the Hippo pathway to stimulate human malignant mesothelioma growth. J. Exp. Med. 209, 479-494.  https://doi.org/10.1084/jem.20111653
  15. Goodman, R.H. and Smolik, S. (2000). CBP/p300 in cell growth, transformation, and development. Genes Dev. 14, 1553-1577.  https://doi.org/10.1101/gad.14.13.1553
  16. Hannon Lab. (2014). FASTX toolkit. Retrieved August 19, 2021, from http://hannonlab.cshl.edu/fastx_toolkit/ 
  17. Hansen, C.G., Moroishi, T., and Guan, K.L. (2015). YAP and TAZ: a nexus for Hippo signaling and beyond. Trends Cell Biol. 25, 499-513.  https://doi.org/10.1016/j.tcb.2015.05.002
  18. Ikushima, H. and Miyazono, K. (2010). TGFbeta signalling: a complex web in cancer progression. Nat. Rev. Cancer 10, 415-424.  https://doi.org/10.1038/nrc2853
  19. Ishida, W., Hamamoto, T., Kusanagi, K., Yagi, K., Kawabata, M., Takehara, K., Sampath, T.K., Kato, M., and Miyazono, K. (2000). Smad6 is a Smad1/5-induced smad inhibitor. Characterization of bone morphogenetic protein-responsive element in the mouse Smad6 promoter. J. Biol. Chem. 275, 6075-6079.  https://doi.org/10.1074/jbc.275.9.6075
  20. Ito, Y., Bae, S.C., and Chuang, L.S. (2015). The RUNX family: developmental regulators in cancer. Nat. Rev. Cancer 15, 81-95.  https://doi.org/10.1038/nrc3877
  21. Ito, Y. and Miyazono, K. (2003). RUNX transcription factors as key targets of TGF-beta superfamily signaling. Curr. Opin. Genet. Dev. 13, 43-47.  https://doi.org/10.1016/S0959-437X(03)00007-8
  22. Jang, J.W., Kim, M.K., Lee, Y.S., Lee, J.W., Kim, D.M., Song, S.H., Lee, J.Y., Choi, B.Y., Min, B., Chi, X.Z., et al. (2017). RAC-LATS1/2 signaling regulates YAP activity by switching between the YAP-binding partners TEAD4 and RUNX3. Oncogene 36, 999-1011.  https://doi.org/10.1038/onc.2016.266
  23. Jozwik, K.M. and Carroll, J.S. (2012). Pioneer factors in hormone-dependent cancers. Nat. Rev. Cancer 12, 381-385.  https://doi.org/10.1038/nrc3263
  24. Kadoch, C. and Crabtree, G.R. (2015). Mammalian SWI/SNF chromatin remodeling complexes and cancer: mechanistic insights gained from human genomics. Sci. Adv. 1, e1500447. 
  25. Kanai, F., Marignani, P.A., Sarbassova, D., Yagi, R., Hall, R.A., Donowitz, M., Hisaminato, A., Fujiwara, T., Ito, Y., Cantley, L.C., et al. (2000). TAZ: a novel transcriptional co-activator regulated by interactions with 14-3-3 and PDZ domain proteins. EMBO J. 19, 6778-6791.  https://doi.org/10.1093/emboj/19.24.6778
  26. Kothapalli, D., Hayashi, N., and Grotendorst, G.R. (1998). Inhibition of TGF-beta-stimulated CTGF gene expression and anchorage-independent growth by cAMP identifies a CTGF-dependent restriction point in the cell cycle. FASEB J. 12, 1151-1161.  https://doi.org/10.1096/fasebj.12.12.1151
  27. Labibi, B., Bashkurov, M., Wrana, J.L., and Attisano, L. (2020). Modeling the control of TGF-beta/Smad nuclear accumulation by the Hippo pathway effectors, Taz/Yap. iScience 23, 101416. 
  28. Lee, J.W., Kim, D.M., Jang, J.W., Park, T.G., Song, S.H., Lee, Y.S., Chi, X.Z., Park, I.Y., Hyun, J.W., Ito, Y., et al. (2019a). RUNX3 regulates cell cycle-dependent chromatin dynamics by functioning as a pioneer factor of the restriction-point. Nat. Commun. 10, 1897. 
  29. Lee, J.W., Lee, Y.S., Kim, M.K., Chi, X.Z., Kim, D., and Bae, S.C. (2023). Role of RUNX3 in restriction point regulation. Cells 12, 708. 
  30. Lee, J.W., Park, T.G., and Bae, S.C. (2019b). Involvement of RUNX3 and BRD family members in restriction point. Mol. Cells 42, 836-839. 
  31. Lee, Y.S., Lee, J.W., Jang, J.W., Chi, X.Z., Kim, J.H., Li, Y.H., Kim, M.K., Kim, D.M., Choi, B.S., Kim, E.G., et al. (2013). Runx3 inactivation is a crucial early event in the development of lung adenocarcinoma. Cancer Cell 24, 603-616.  https://doi.org/10.1016/j.ccr.2013.10.003
  32. Lee, Y.S., Lee, J.W., Somg, S.H., Kim, D.M., Lee, J.W., Chi, X.Z., Ito, Y., and Bae, S.C. (2020). K-Ras-activated cells can develop into lung tumors when Runx3-mediated tumor suppressor pathways are abrogated. Mol. Cells 43, 889-897. 
  33. Li, Q.L., Ito, K., Sakakura, C., Fukamachi, H., Inoue, K., Chi, X.Z., Lee, K.Y., Nomura, S., Lee, C.W., Han, S.B., et al. (2002). Causal relationship between the loss of RUNX3 expression and gastric cancer. Cell 109, 113-124.  https://doi.org/10.1016/S0092-8674(02)00690-6
  34. Liu, X., Li, H., Rajurkar, M., Li, Q., Cotton, J.L., Ou, J., Zhu, L.J., Goel, H.L., Mercurio, A.M., Park, J.S., et al. (2016). Tead and AP1 coordinate transcription and motility. Cell Rep. 14, 1169-1180.  https://doi.org/10.1016/j.celrep.2015.12.104
  35. Liu-Chittenden, Y., Huang, B., Shim, J.S., Chen, Q., Lee, S.J., Anders, R.A., Liu, J.O., and Pan, D. (2012). Genetic and pharmacological disruption of the TEAD-YAP complex suppresses the oncogenic activity of YAP. Genes Dev. 26, 1300-1305.  https://doi.org/10.1101/gad.192856.112
  36. Malumbres, M. and Barbacid, M. (2001). To cycle or not to cycle: a critical decision in cancer. Nat. Rev. Cancer 1, 222-231.  https://doi.org/10.1038/35106065
  37. Massague, J. (2008). TGFbeta in cancer. Cell 134, 215-230.  https://doi.org/10.1016/j.cell.2008.07.001
  38. Miller, D.S.J., Schmierer, B., and Hill, C.S. (2019). TGF-beta family ligands exhibit distinct signalling dynamics that are driven by receptor localisation. J. Cell Sci. 132, jcs234039. 
  39. Miller, E., Yang, J., DeRan, M., Wu, C., Su, A.I., Bonamy, G.M., Liu, J., Peters, E.C., and Wu, X. (2012). Identification of serum-derived sphingosine-1-phosphate as a small molecule regulator of YAP. Chem. Biol. 19, 955-962.  https://doi.org/10.1016/j.chembiol.2012.07.005
  40. Nagarajan, R.P., Zhang, J., Li, W., and Chen, Y. (1999). Regulation of Smad7 promoter by direct association with Smad3 and Smad4. J. Biol. Chem. 274, 33412-33418.  https://doi.org/10.1074/jbc.274.47.33412
  41. Nakamura, R., Hiwatashi, N., Bing, R., Doyle, C.P., and Branski, R.C. (2021). Concurrent YAP/TAZ and SMAD signaling mediate vocal fold fibrosis. Sci. Rep. 11, 13484. 
  42. Nakao, A., Imamura, T., Souchelnytskyi, S., Kawabata, M., Ishisaki, A., Oeda, E., Tamaki, K., Hanai, J., Heldin, C.H., Miyazono, K., et al. (1997). TGF-beta receptor-mediated signalling through Smad2, Smad3 and Smad4. EMBO J. 16, 5353-5362.  https://doi.org/10.1093/emboj/16.17.5353
  43. Onodera, Y., Teramura, T., Takehara, T., and Fukuda, K. (2019). Transforming growth factor beta-activated kinase 1 regulates mesenchymal stem cell proliferation through stabilization of Yap1/Taz proteins. Stem Cells 37, 1595-1605.  https://doi.org/10.1002/stem.3083
  44. Pan, D. (2010). The hippo signaling pathway in development and cancer. Dev. Cell 19, 491-505.  https://doi.org/10.1016/j.devcel.2010.09.011
  45. Pardee, A.B. (1974). A restriction point for control of normal animal cell proliferation. Proc. Natl. Acad. Sci. U. S. A. 71, 1286-1290.  https://doi.org/10.1073/pnas.71.4.1286
  46. Pearson, J.D., Huang, K., Pacal, M., McCurdy, S.R., Lu, S., Aubry, A., Yu, T., Wadosky, K.M., Zhang, L., Wang, T., et al. (2021). Binary pan-cancer classes with distinct vulnerabilities defined by pro- or anti-cancer YAP/TEAD activity. Cancer Cell 39, 1115-1134.e12.  https://doi.org/10.1016/j.ccell.2021.06.016
  47. Qiao, Y., Lin, S.J., Chen, Y., Voon, D.C., Zhu, F., Chuang, L.S., Wang, T., Tan, P., Lee, S.C., Yeoh, K.G., et al. (2016). RUNX3 is a novel negative regulator of oncogenic TEAD-YAP complex in gastric cancer. Oncogene 35, 2664-2674.  https://doi.org/10.1038/onc.2015.338
  48. R Core Team (2020). R: A Language and Environment for Statistical Computing (Vienna, Austria: R Foundation for Statistical Computing).
  49. Reddy, B.V. and Irvine, K.D. (2013). Regulation of Hippo signaling by EGFRMAPK signaling through Ajuba family proteins. Dev. Cell 24, 459-471.  https://doi.org/10.1016/j.devcel.2013.01.020
  50. Ren, F., Zhang, L., and Jiang, J. (2010). Hippo signaling regulates Yorkie nuclear localization and activity through 14-3-3 dependent and independent mechanisms. Dev. Biol. 337, 303-312.  https://doi.org/10.1016/j.ydbio.2009.10.046
  51. Roberts, A., Trapnell, C., Donaghey, J., Rinn, J.L., and Pachter, L. (2011). Improving RNA-Seq expression estimates by correcting for fragment bias. Genome Biol. 12, R22. 
  52. Santoro, R., Zanotto, M., Simionato, F., Zecchetto, C., Merz, V., Cavallini, C., Piro, G., Sabbadini, F., Boschi, F., Scarpa, A., et al. (2020). Modulating TAK1 expression inhibits YAP and TAZ oncogenic functions in pancreatic cancer. Mol. Cancer Ther. 19, 247-257.  https://doi.org/10.1158/1535-7163.MCT-19-0270
  53. Schlegelmilch, K., Mohseni, M., Kirak, O., Pruszak, J., Rodriguez, J.R., Zhou, D., Kreger, B.T., Vasioukhin, V., Avruch, J., Brummelkamp, T.R., et al. (2011). Yap1 acts downstream of alpha-catenin to control epidermal proliferation. Cell 144, 782-795.  https://doi.org/10.1016/j.cell.2011.02.031
  54. Shi, Y. and Massague, J. (2003). Mechanisms of TGF-beta signaling from cell membrane to the nucleus. Cell 113, 685-700.  https://doi.org/10.1016/S0092-8674(03)00432-X
  55. Simon, A. (2010). FastQC. Retrieved August 19, 2021, from https://www.bioinformatics.babraham.ac.uk/projects/fastqc/ 
  56. Sudol, M., Bork, P., Einbond, A., Kastury, K., Druck, T., Negrini, M., Huebner, K., and Lehman, D. (1995). Characterization of the mammalian YAP (Yes-associated protein) gene and its role in defining a novel protein module, the WW domain. J. Biol. Chem. 270, 14733-14741.  https://doi.org/10.1074/jbc.270.24.14733
  57. Trapnell, C., Pachter, L., and Salzberg, S.L. (2009). TopHat: discovering splice junctions with RNA-Seq. Bioinformatics 25, 1105-1111.  https://doi.org/10.1093/bioinformatics/btp120
  58. Varelas, X. (2014). The Hippo pathway effectors TAZ and YAP in development, homeostasis and disease. Development 141, 1614-1626.  https://doi.org/10.1242/dev.102376
  59. Varelas, X., Miller, B.W., Sopko, R., Song, S., Gregorieff, A., Fellouse, F.A., Sakuma, R., Pawson, T., Hunziker, W., McNeill, H., et al. (2010). The Hippo pathway regulates Wnt/beta-catenin signaling. Dev. Cell 18, 579-591.  https://doi.org/10.1016/j.devcel.2010.03.007
  60. Varelas, X., Sakuma, R., Samavarchi-Tehrani, P., Peerani, R., Rao, B.M., Dembowy, J., Yaffe, M.B., Zandstra, P.W., and Wrana, J.L. (2008). TAZ controls Smad nucleocytoplasmic shuttling and regulates human embryonic stem-cell self-renewal. Nat. Cell Biol. 10, 837-848.  https://doi.org/10.1038/ncb1748
  61. Wang, H., Wang, L., Erdjument-Bromage, H., Vidal, M., Tempst, P., Jones, R.S., and Zhang, Y. (2004). Role of histone H2A ubiquitination in Polycomb silencing. Nature 431, 873-878.  https://doi.org/10.1038/nature02985
  62. Weinberg, R.A. (2007). pRb and control of the cell cycle clock. In The Biology of Cancer, R.A. Weinberg, ed. (New York: Garland Sciences), pp. 275-329. 
  63. Yagi, R., Chen, L.F., Shigesada, K., Murakami, Y., and Ito, Y. (1999). A WW domain-containing yes-associated protein (YAP) is a novel transcriptional co-activator. EMBO J. 18, 2551-2562.  https://doi.org/10.1093/emboj/18.9.2551
  64. Yin, F., Yu, J., Zheng, Y., Chen, Q., Zhang, N., and Pan, D. (2013). Spatial organization of Hippo signaling at the plasma membrane mediated by the tumor suppressor Merlin/NF2. Cell 154, 1342-1355.  https://doi.org/10.1016/j.cell.2013.08.025
  65. Yu, F.X., Zhao, B., Panupinthu, N., Jewell, J.L., Lian, I., Wang, L.H., Zhao, J., Yuan, H., Tumaneng, K., Li, H., et al. (2012). Regulation of the Hippo-YAP pathway by G-protein-coupled receptor signaling. Cell 150, 780-791.  https://doi.org/10.1016/j.cell.2012.06.037
  66. Zanconato, F., Cordenonsi, M., and Piccolo, S. (2016). YAP/TAZ at the roots of cancer. Cancer Cell 29, 783-803.  https://doi.org/10.1016/j.ccell.2016.05.005
  67. Zanconato, F., Forcato, M., Battilana, G., Azzolin, L., Quaranta, E., Bodega, B., Rosato, A., Bicciato, S., Cordenonsi, M., and Piccolo, S. (2015). Genome-wide association between YAP/TAZ/TEAD and AP-1 at enhancers drives oncogenic growth. Nat. Cell Biol. 17, 1218-1227.  https://doi.org/10.1038/ncb3216
  68. Zhang, H., Pasolli, H.A., and Fuchs, E. (2011). Yes-associated protein (YAP) transcriptional coactivator functions in balancing growth and differentiation in skin. Proc. Natl. Acad. Sci. U. S. A. 108, 2270-2275.  https://doi.org/10.1073/pnas.1019603108
  69. Zhang, X., Milton, C.C., Humbert, P.O., and Harvey, K.F. (2009). Transcriptional output of the Salvador/warts/hippo pathway is controlled in distinct fashions in Drosophila melanogaster and mammalian cell lines. Cancer Res. 69, 6033-6041.  https://doi.org/10.1158/0008-5472.CAN-08-4592
  70. Zhang, Y., Feng, X.H., and Derynck, R. (1998). Smad3 and Smad4 cooperate with c-Jun/c-Fos to mediate TGF-beta-induced transcription. Nature 394, 909-913.  https://doi.org/10.1038/29814
  71. Zhao, B., Wei, X., Li, W., Udan, R.S., Yang, Q., Kim, J., Xie, J., Ikenoue, T., Yu, J., Li, L., et al. (2007). Inactivation of YAP oncoprotein by the Hippo pathway is involved in cell contact inhibition and tissue growth control. Genes Dev. 21, 2747-2761.  https://doi.org/10.1101/gad.1602907
  72. Zhao, B., Ye, X., Yu, J., Li, L., Li, W., Li, S., Yu, J., Lin, J.D., Wang, C.Y., Chinnaiyan, A.M., et al. (2008). TEAD mediates YAP-dependent gene induction and growth control. Genes Dev. 22, 1962-1971.  https://doi.org/10.1101/gad.1664408