Akt Phosphorylates the Yes-Associated Protein, YAP, to Induce Interaction with 14-3-3 and Attenuation of p73-Mediated Apoptosis
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We have used an affinity purification method to identify substrates of protein kinase B/Akt. One protein that associates with 14-3-3 in an Akt-dependent manner is shown here to be the Yes-associated protein (YAP), which is phosphorylated by Akt at serine 127, leading to binding to 14-3-3. Akt promotes YAP localization to the cytoplasm, resulting in loss from the nucleus where it functions as a coactivator of transcription factors including p73. p73-mediated induction of Bax expression following DNA damage requires YAP function and is attenuated by Akt phosphorylation of YAP. YAP overexpression increases, while YAP depletion decreases, p73-mediated apoptosis following DNA damage, in an Akt inhibitable manner. Akt phosphorylation of YAP may thus suppress the induction of the proapoptotic gene expression response following cellular damage.
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Akt was initially shown to phosphorylate Yap on Ser127, but this finding was not confirmed by subsequent studies.
“Akt was initially shown to phosphorylate Yap on Ser127 (13) but this finding was not confirmed by subsequent studies.”
From The Hippo signal transduction network for exercise physiologists (2016) · cites this paper as [13]
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Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells
Elbashir, S. M., Harborth, J., Lendeckel, W., Yalcin, A., Weber, K., & Tuschl, T. (2001) · Nature · doi:10.1038/35078107 · Cited by 9,456 · see citing works
Akt Promotes Cell Survival by Phosphorylating and Inhibiting a Forkhead Transcription Factor
Brunet, A., Bonni, A., Zigmond, M. J., Lin, M. Z., Juo, P., Hu, L. S., Anderson, M. J., Arden, K. C., Blenis, J., & Greenberg, M. E. (1999) · Cell · doi:10.1016/s0092-8674(00)80595-4 · Cited by 6,535 · see citing works
Akt phosphorylation of BAD couples survival signals to the cell-intrinsic death machinery
Datta, S. R., Dudek, H., Tao, X., Masters, S., Fu, H., Gotoh, Y., & Greenberg, M. E. (1997) · Cell · doi:10.1016/s0092-8674(00)80405-5 · Cited by 5,689 · see citing works
Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B
Cross, D. A. E., Alessi, D. R., Cohen, P., Andjelkovich, M., & Hemmings, B. A. (1995) · Nature · doi:10.1038/378785a0 · Cited by 5,244 · see citing works
Extension of Life-Span by Introduction of Telomerase into Normal Human Cells
Bodnar, A. G., Ouellette, M., Frolkis, M., Holt, S. E., Chiu, C.-P., Morin, G. B., Harley, C. B., Shay, J. W., Lichtsteiner, S., & Wright, W. E. (1998) · Science · doi:10.1126/science.279.5349.349 · Cited by 4,975 · see citing works
Cellular survival: a play in three Akts
Datta, S. R., Brunet, A., & Greenberg, M. E. (1999) · Genes & Development · doi:10.1101/gad.13.22.2905 · Cited by 4,216 · see citing works
Vlahos, C. J., Matter, W. F., Hui, K. Y., & Brown, R. F. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)37680-9 · Cited by 3,248 · see citing works
A generic protein purification method for protein complex characterization and proteome exploration
Rigaut, G., Shevchenko, A., Rutz, B., Wilm, M., Mann, M., & Séraphin, B. (1999) · Nature Biotechnology · doi:10.1038/13732 · Cited by 2,707 · see citing works
Interleukin-3-Induced Phosphorylation of BAD Through the Protein Kinase Akt
del Peso, L., González‐García, M., Page, C., Herrera, R., & Núñez, G. (1997) · Science · doi:10.1126/science.278.5338.687 · Cited by 2,213 · see citing works
The Structural Basis for 14-3-3:Phosphopeptide Binding Specificity
Yaffe, M. B., Rittinger, K., Volinia, S., Caron, P. R., Aitken, A., Leffers, H. C. B., Gamblin, S. J., Smerdon, S. J., & Cantley, L. C. (1997) · Cell · doi:10.1016/s0092-8674(00)80487-0 · Cited by 1,604 · see citing works
Mayo, L. D., & Donner, D. B. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.181181198 · Cited by 1,230 · see citing works
Ten years of protein kinase B signalling: a hard Akt to follow
Brazil, D. P., & Hemmings, B. A. (2001) · Trends in Biochemical Sciences · doi:10.1016/s0968-0004(01)01958-2 · Cited by 1,177 · see citing works
Direct control of the Forkhead transcription factor AFX by protein kinase B
Kops, G. J. P. L., de Ruiter, N. D., de Vries-Smits, A. M. M., Powell, D. R., Bos, J. L., & Burgering, B. M. T. (1999) · Nature · doi:10.1038/19328 · Cited by 1,085 · see citing works
Khwaja, A., Rodriguez‐Viciana, P., Wennström, S., Warne, P. H., & Downward, J. (1997) · The EMBO Journal · doi:10.1093/emboj/16.10.2783 · Cited by 1,039 · see citing works
Self-citationHER-2/neu induces p53 ubiquitination via Akt-mediated MDM2 phosphorylation
Zhou, B. P., Liao, Y., Xia, W., Zou, Y., Spohn, B., & Hung, M.-C. (2001) · Nature Cell Biology · doi:10.1038/ncb1101-973 · Cited by 951 · see citing works
The tyrosine kinase c-Abl regulates p73 in apoptotic response to cisplatin-induced DNA damage
Gong, J., Costanzo, A., Yang, H., Melino, G., Kaelin, W. G., Levrero, M., & Wang, J. Y. J. (1999) · Nature · doi:10.1038/21690 · Cited by 923 · see citing works
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) · The EMBO Journal · doi:10.1093/emboj/19.24.6778 · Cited by 758 · see citing works
Vassilev, A., Kaneko, K. J., Shu, H., Zhao, Y., & DePamphilis, M. L. (2001) · Genes & Development · doi:10.1101/gad.888601 · Cited by 719 · see citing works
Jiang, X., Jimenez, G. S., Chang, E., Frolkis, M., Kusler, B., Sage, M., Beeche, M., Bodnar, A. G., Wahl, G. M., Tlsty, T. D., et al. (1999) · Nature Genetics · doi:10.1038/5056 · Cited by 668 · see citing works
ASPP Proteins Specifically Stimulate the Apoptotic Function of p53
Samuels-Lev, Y., O'Connor, D. J., Bergamaschi, D., Trigiante, G., Hsieh, J.-K., Zhong, S., Campargue, I., Naumovski, L., Crook, T., & Lu, X. (2001) · Molecular Cell · doi:10.1016/s1097-2765(01)00367-7 · Cited by 664 · see citing works
Alessi, D. R., Barry Caudwell, F., Andjelkovic, M., Hemmings, B. A., & Cohen, P. (1996) · FEBS Letters · doi:10.1016/s0014-5793(96)01370-1 · Cited by 628 · see citing works
PKB/AKT: functional insights from genetic models
Scheid, M. P., & Woodgett, J. R. (2001) · Nature Reviews Molecular Cell Biology · doi:10.1038/35096067 · Cited by 608 · see citing works
p73 is regulated by tyrosine kinase c-Abl in the apoptotic response to DNA damage
Yuan, Z.-M., Shioya, H., Ishiko, T., Sun, X., Gu, J., Huang, Y., Lu, H., Kharbanda, S. M., Weichselbaum, R. W., & Kufe, D. W. (1999) · Nature · doi:10.1038/21704 · Cited by 574 · see citing works
A WW domain‐containing Yes‐associated protein (YAP) is a novel transcriptional co‐activator
Yagi, R., Chen, L. F., Shigesada, K., Murakami, Y., & Ito, Y. (1999) · The EMBO Journal · doi:10.1093/emboj/18.9.2551 · Cited by 553 · see citing works
The Serine Protease Omi/HtrA2 Regulates Apoptosis by Binding XIAP through a Reaper-like Motif
Martins, L. M., Iaccarino, I., Tenev, T., Gschmeissner, S., Totty, N. F., Lemoine, N. R., Savopoulos, J. W., Gray, C. W., Creasy, C. L., Dingwall, C., et al. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m109784200 · Cited by 544 · see citing works
Self-citationPhysical Interaction with Yes-associated Protein Enhances p73 Transcriptional Activity
Strano, S., Munarriz, E. R., Rossi, M., Castagnoli, L., Shaul, Y., Sacchi, A., Oren, M., Sudol, M., Cesareni, G., & Blandino, G. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m010484200 · Cited by 418 · see citing works
Self-citation(1994) · PubMed · Cited by 404 · see citing works
Self-citationPeptide and Protein Library Screening Defines Optimal Substrate Motifs for AKT/PKB
Obata, T., Yaffe, M. B., Leparc, G., Piro, E. T., Maegawa, H., Kashiwagi, A., Kikkawa, R., & Cantley, L. C. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m005497200 · Cited by 388 · see citing works
Sudol, M., Bork, P., Einbond, A., Kastury, K., Druck, T., Negrini, M., Huebner, K., & Lehman, D. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.24.14733 · Cited by 342 · see citing works
Self-citationKohn, A. D., Barthel, A., Kovacina, K., Boge, A., Wallach, B., Summers, S., Birnbaum, M., Scott, P. H., Lawrence, J., & Roth, R. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.19.11937 · Cited by 340 · see citing works
Watton, S. J., & Downward, J. (1999) · Current Biology · doi:10.1016/s0960-9822(99)80192-4 · Cited by 298 · see citing works
Self-citationWennström, S., & Downward, J. (1999) · Molecular and Cellular Biology · doi:10.1128/mcb.19.6.4279 · Cited by 279 · see citing works
Self-citationPhosphoprotein Analysis Using Antibodies Broadly Reactive against Phosphorylated Motifs
Zhang, H., Zha, X., Tan, Y., Hornbeck, P. V., Mastrangelo, A. J., Alessi, D. R., Polakiewicz, R. D., & Comb, M. J. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m206399200 · Cited by 271 · see citing works
Inhibition of the anti-apoptotic PI(3)K/Akt/Bad pathway by stressPreprint
ZUNDEL, W. S., & Giaccia, A. J. (1998) · Genes & Development · doi:10.1101/gad.12.13.1941 · Cited by 212 · see citing works
Mohler, P. J., Kreda, S. M., Boucher, R. C., Sudol, M., Stutts, M. J., & Milgram, S. L. (1999) · The Journal of Cell Biology · doi:10.1083/jcb.147.4.879 · Cited by 180 · see citing works
Self-citationYes-associated Protein and p53-binding Protein-2 Interact through Their WW and SH3 Domains
Espanel, X., & Sudol, M. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m008568200 · Cited by 135 · see citing works
Self-citationStrano, S., Rossi, M., Fontemaggi, G., Munarriz, E. R., Soddu, S., Sacchi, A., & Blandino, G. (2001) · FEBS Letters · doi:10.1016/s0014-5793(01)02119-6 · Cited by 87 · see citing works
Stiewe, T., & Pützer, B. M. (2001) · APOPTOSIS · doi:10.1023/a:1012433522902 · Cited by 63 · see citing works
Yuan, R., Fan, S., Achary, M. P., Stewart, D. M., Goldberg, I. D., & Rosen, E. M. (2001) · PubMed · Cited by 38 · see citing works
Loss of p73 Induction in a Cisplatin-Resistant Bladder Cancer Cell Line
Ono, Y., Nonomura, N., Harada, Y., Fukui, T., Tokizane, T., Sato, E., Nakayama, M., Nishimura, K., Takahara, S., & Okuyama, A. (2001) · Molecular Urology · doi:10.1089/109153601750124267 · Cited by 20 · see citing works
Flagged first, then by citations
1 of the 41 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Zhao, B., Wei, X., Li, W., Udan, R. S., Yang, Q., Kim, J., Xie, J., Ikenoue, T., Yu, J., Li, L., et al. (2007) · Genes & Development · doi:10.1101/gad.1602907 · Cited by 3,092 · see citing works
TEAD mediates YAP-dependent gene induction and growth control
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) · Genes & Development · doi:10.1101/gad.1664408 · Cited by 2,498 · see citing works
The Hippo Signaling Pathway in Development and Cancer
Pan, D. (2010) · Developmental Cell · doi:10.1016/j.devcel.2010.09.011 · Cited by 2,274 · see citing works
Elucidation of a universal size-control mechanism in Drosophila and mammals
Dong, J., Feldmann, G., Huang, J., Wu, S., Zhang, N., Comerford, S. A., Gayyed, M. F., Anders, R. A., Maitra, A., & Pan, D. (2007) · Cell · doi:10.1016/j.cell.2007.07.019 · Cited by 2,370 · see citing works
The activation of Akt/PKB signaling pathway and cell survival
Song, G., Ouyang, G., & Bao, S. (2005) · Journal of Cellular and Molecular Medicine · doi:10.1111/j.1582-4934.2005.tb00337.x · Cited by 1,891 · see citing works
Huang, J., Wu, S., Barrera, J. A., Matthews, K. A., & Pan, D. (2005) · Cell · doi:10.1016/j.cell.2005.06.007 · Cited by 1,870 · see citing works
The Biology of YAP/TAZ: Hippo Signaling and Beyond
Piccolo, S., Dupont, S., & Cordenonsi, M. (2014) · Physiological Reviews · doi:10.1152/physrev.00005.2014 · Cited by 1,797 · see citing works
Calvo, F., Ege, N., Grande-Garcia, A., Hooper, S., Jenkins, R. P., Chaudhry, S. I., Harrington, K., Williamson, P., Moeendarbary, E., Charras, G., et al. (2013) · Nature Cell Biology · doi:10.1038/ncb2756 · Cited by 1,478 · see citing works
Force triggers YAP nuclear entry by regulating transport across nuclear pores
Elosegui-Artola, A., Andreu, I., Beedle, A. E. M., Lezamiz, A., Uroz, M., Kosmalska, A. J., Oria, R., Kechagia, J. Z., Rico-Lastres, P., Le Roux, A.-L., et al. (2017) · Cell · doi:10.1016/j.cell.2017.10.008 · Cited by 1,491 · see citing works
YAP1 increases organ size and expands undifferentiated progenitor cells
Camargo, F. D., Gokhale, S., Johnnidis, J. B., Fu, D., Bell, G. W., Jaenisch, R., & Brummelkamp, T. R. (2007) · Current Biology · doi:10.1016/j.cub.2007.10.039 · Cited by 1,252 · see citing works
Nishioka, N., Inoue, K., Adachi, K., Kiyonari, H., Ota, M., Ralston, A., Yabuta, N., Hirahara, S., Stephenson, R. O., Ogonuki, N., et al. (2009) · Developmental Cell · doi:10.1016/j.devcel.2009.02.003 · Cited by 1,083 · see citing works
Identification and validation of oncogenes in liver cancer using an integrative oncogenomic approach
Zender, L., Spector, M. S., Xue, W., Flemming, P., Cordon-Cardo, C., Silke, J., Fan, S.-T., Luk, J. M., Wigler, M., Hannon, G. J., et al. (2006) · Cell · doi:10.1016/j.cell.2006.05.030 · Cited by 1,065 · see citing works
Lei, Q., Zhang, H., Zhao, B., Zha, Z., Bai, F., Pei, X., Zhao, S., Xiong, Y., & Guan, K. (2008) · Molecular and Cellular Biology · doi:10.1128/mcb.01874-07 · Cited by 925 · see citing works
Transforming properties of YAP , a candidate oncogene on the chromosome 11q22 amplicon
Overholtzer, M., Zhang, J., Smolen, G. A., Muir, B., Li, W., Sgroi, D. C., Deng, C., Brugge, J. S., & Haber, D. A. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0605579103 · Cited by 885 · see citing works
Phosphorylation of β-Catenin by AKT Promotes β-Catenin Transcriptional Activity*
Fang, D.-X., Hawke, D., Zheng, Y., Xia, Y., Meisenhelder, J., Nika, H., Mills, G., Kobayashi, R., Hunter, T., & Lu, Z. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m611871200 · Cited by 774 · see citing works
Advances in protein kinase B signalling: AKTion on multiple fronts
Brazil, D. P., Yang, Z., & Hemmings, B. A. (2004) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2004.03.006 · Cited by 826 · see citing works
Tumor Suppressor LATS1 Is a Negative Regulator of Oncogene YAP
Hao, Y., Chun, A., Cheung, K. J., Rashidi, B., & Yang, X. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m709037200 · Cited by 780 · see citing works
PI 3-kinase, Akt and cell survival
Downward, J. (2004) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2004.01.002 · Cited by 783 · see citing works
Self-citationThe role of YAP transcription coactivator in regulating stem cell self-renewal and differentiationPreprint
Lian, I., Kim, J., Okazawa, H., Zhao, J. J., Zhao, B., Yu, J., Chinnaiyan, A. M., Israel, M. A., Goldstein, L. S. B., Abujarour, R., et al. (2010) · Genes & Development · doi:10.1101/gad.1903310 · Cited by 738 · see citing works
FoxO transcription factors; Regulation by AKT and 14-3-3 proteins
Tzivion, G., Dobson, M., & Ramakrishnan, G. (2011) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2011.06.002 · Cited by 728 · see citing works
Structure, regulation and function of PKB/AKT—a major therapeutic target
Hanada, M., Feng, J., & Hemmings, B. A. (2003) · Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics · doi:10.1016/j.bbapap.2003.11.009 · Cited by 719 · see citing works
The Hippo pathway effectors TAZ and YAP in development, homeostasis and disease
Varelas, X. (2014) · Development · doi:10.1242/dev.102376 · Cited by 665 · see citing works
The Hippo pathway target, YAP, promotes metastasis through its TEAD-interaction domain
Lamar, J. M., Stern, P., Liu, H., Schindler, J. W., Jiang, Z.-G., & Hynes, R. O. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1212021109 · Cited by 656 · see citing works
Hippo signaling in organ size controlPreprint
Pan, D. (2007) · Genes & Development · doi:10.1101/gad.1536007 · Cited by 648 · see citing works
Mechanical regulation of bone remodeling
Wang, L., You, X., Zhang, L., Zhang, C., & Zou, W. (2022) · Bone Research · doi:10.1038/s41413-022-00190-4 · Cited by 641 · see citing works
The TEAD/TEF family of transcription factor Scalloped mediates Hippo signaling in organ size control
Zhang, L., Ren, F., Zhang, Q., Chen, Y., Wang, B., & Jiang, J. (2008) · Developmental Cell · doi:10.1016/j.devcel.2008.01.006 · Cited by 630 · see citing works
The Salvador–Warts–Hippo pathway — an emerging tumour-suppressor network
Harvey, K., & Tapon, N. (2007) · Nature Reviews Cancer · doi:10.1038/nrc2070 · Cited by 628 · see citing works
14-3-3 proteins in the nervous system
Berg, D., Holzmann, C., & Rieß, O. (2003) · Nature reviews. Neuroscience · doi:10.1038/nrn1197 · Cited by 619 · see citing works
YAP and TAZ: a nexus for Hippo signaling and beyond
Hansen, C. G., Moroishi, T., & Guan, K. (2015) · Trends in Cell Biology · doi:10.1016/j.tcb.2015.05.002 · Cited by 573 · see citing works
Control of Cell Proliferation and Apoptosis by Mob as Tumor Suppressor, Mats
Lai, Z.-C., Wei, X., Shimizu, T., Ramos, E., Rohrbaugh, M., Nikolaidis, N., Ho, L., & Li, Y. (2005) · Cell · doi:10.1016/j.cell.2004.12.036 · Cited by 570 · see citing works
The Hippo Pathway Regulates Wnt/β-Catenin Signaling
Varelas, X., Miller, B. W., Sopko, R., Song, S., Gregorieff, A., Fellouse, F. A., Sakuma, R., Pawson, T. J., Hunziker, W., McNeill, H., et al. (2010) · Developmental Cell · doi:10.1016/j.devcel.2010.03.007 · Cited by 571 · see citing works
Dynamic interactions between 14-3-3 proteins and phosphoproteins regulate diverse cellular processes
MacKintosh, C. (2004) · Biochemical Journal · doi:10.1042/bj20031332 · Cited by 527 · see citing works
The YAP and TAZ transcription co-activators: Key downstream effectors of the mammalian Hippo pathway
Hong, W., & Guan, K. (2012) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2012.05.004 · Cited by 497 · see citing works
p63 and p73: Roles in Development and Tumor Formation
Moll, U. M., & Slade, N. (2004) · Molecular Cancer Research · doi:10.1158/1541-7786.371.2.7 · Cited by 482 · see citing works
Dougherty, M. K., & Morrison, D. K. (2004) · Journal of Cell Science · doi:10.1242/jcs.01171 · Cited by 457 · see citing works
Komuro, A., Nagai, M., Navin, N. E., & Sudol, M. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m305597200 · Cited by 459 · see citing works
Self-citationTRAIL signalling: Decisions between life and death
Falschlehner, C., Emmerich, C. H., Gerlach, B., & Walczak, H. (2007) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2007.02.007 · Cited by 458 · see citing works
The Hippo–YAP pathway: new connections between regulation of organ size and cancer
Zhao, B., Lei, Q., & Guan, K. (2008) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2008.10.001 · Cited by 456 · see citing works
Mîinea, C. P., Sano, H., Kane, S., Sano, E., Fukuda, M., Peränen, J., Lane, W. S., & Lienhard, G. E. (2005) · Biochemical Journal · doi:10.1042/bj20050887 · Cited by 449 · see citing works
RUBIO, M. P., Geraghty, K. M., WONG, B. H. C., Wood, N. T., Campbell, D. G., MORRICE, N. A., & MacKintosh, C. (2004) · Biochemical Journal · doi:10.1042/bj20031797 · Cited by 443 · see citing works
Hermeking, H. (2003) · Nature reviews. Cancer · doi:10.1038/nrc1230 · Cited by 434 · see citing works
Zeng, Q., & Hong, W. (2008) · Cancer Cell · doi:10.1016/j.ccr.2008.02.011 · Cited by 436 · see citing works
FAK signaling in human cancer as a target for therapeutics
Lee, B. Y., Timpson, P., Horvath, L. G., & Daly, R. J. (2014) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2014.10.001 · Cited by 431 · see citing works
Morin-Kensicki, E. M., Boone, B. N., Howell, M., Stonebraker, J. R., Teed, J., Alb, J. G., Magnuson, T. R., O'Neal, W., & Milgram, S. L. (2006) · Molecular and Cellular Biology · doi:10.1128/mcb.26.1.77-87.2006 · Cited by 429 · see citing works
The critical role of Akt in cardiovascular function
Abeyrathna, P., & Su, Y. (2015) · Vascular Pharmacology · doi:10.1016/j.vph.2015.05.008 · Cited by 428 · see citing works
Adhesion to fibronectin regulates Hippo signaling via the FAK–Src–PI3K pathway
Kim, N., & Gumbiner, B. M. (2015) · The Journal of Cell Biology · doi:10.1083/jcb.201501025 · Cited by 424 · see citing works
Kinomics: methods for deciphering the kinome
Johnson, S. A., & Hunter, T. R. (2004) · Nature Methods · doi:10.1038/nmeth731 · Cited by 420 · see citing works
Matallanas, D., Romano, D., Yee, K. S. Y., Meissl, K., Kučerová, L., Piazzolla, D., Baccarini, M., Vass, J. K., Kölch, W., & O’Neill, E. E. (2007) · Molecular Cell · doi:10.1016/j.molcel.2007.08.008 · Cited by 416 · see citing works
In vivo regulation of Yorkie phosphorylation and localization
Oh, H., & Irvine, K. D. (2008) · Development · doi:10.1242/dev.015255 · Cited by 404 · see citing works
Zaidi, S. K., Sullivan, A. J., Medina, R., Ito, Y., van Wijnen, A. J., Stein, J. L., Lian, J. B., & Stein, G. S. (2004) · The EMBO Journal · doi:10.1038/sj.emboj.7600073 · Cited by 401 · see citing works
Raf Family Kinases: Old Dogs Have Learned New Tricks
Matallanas, D., Birtwistle, M. R., Romano, D., Zebisch, A., Rauch, J., von Kriegsheim, A., & Kölch, W. (2011) · Genes & Cancer · doi:10.1177/1947601911407323 · Cited by 383 · see citing works
Hippo Pathway-independent Restriction of TAZ and YAP by Angiomotin
Chan, S. W., Lim, C. J., Chong, Y. F., Pobbati, A. V., Huang, C., & Hong, W. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.c110.212621 · Cited by 386 · see citing works
The Hippo pathway in the heart: pivotal roles in development, disease, and regeneration
Wang, J., Liu, S., Heallen, T. R., & Martin, J. F. (2018) · Nature Reviews Cardiology · doi:10.1038/s41569-018-0063-3 · Cited by 383 · see citing works
The transcriptional coactivator TAZ regulates mesenchymal differentiation in malignant gliomaPreprint
Bhat, K., Salazar, K. L., Balasubramaniyan, V., Wani, K., Heathcock, L. E., Hollingsworth, F., James, J. D., Gumin, J., Alfaro-Munoz, K. D., Kim, S. H., et al. (2011) · Genes & Development · doi:10.1101/gad.176800.111 · Cited by 377 · see citing works
YAP/TAZ functions and their regulation at a glance
Pocaterra, A., Romani, P., & Dupont, S. (2020) · Journal of Cell Science · doi:10.1242/jcs.230425 · Cited by 369 · see citing works
Mst2 and Lats Kinases Regulate Apoptotic Function of Yes Kinase-associated Protein (YAP)
Oka, T., Mazack, V., & Sudol, M. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m804380200 · Cited by 368 · see citing works
Self-citationSaucedo, L. J., & Edgar, B. A. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2221 · Cited by 363 · see citing works
Strano, S., Monti, O., Pediconi, N., Baccarini, A., Fontemaggi, G., Lapi, E., Mantovani, F., Damalas, A., Citro, G., Sacchi, A., et al. (2005) · Molecular Cell · doi:10.1016/j.molcel.2005.04.008 · Cited by 360 · see citing works
Levy, D., Adamovich, Y., Reuven, N. B., & Shaul, Y. (2008) · Molecular Cell · doi:10.1016/j.molcel.2007.12.022 · Cited by 348 · see citing works
Martelli, A. M., Nyåkern, M., Tabellini, G., Bortul, R., Tazzari, P. L., Evangelisti, C., & Cocco, L. (2006) · Leukemia · doi:10.1038/sj.leu.2404245 · Cited by 344 · see citing works
The Hippo-YAP signaling pathway and contact inhibition of growth
Gumbiner, B. M., & Kim, N. (2014) · Journal of Cell Science · doi:10.1242/jcs.140103 · Cited by 338 · see citing works
The role of p53 in chemosensitivity and radiosensitivity
El‐Deiry, W. S. (2003) · Oncogene · doi:10.1038/sj.onc.1206949 · Cited by 337 · see citing works
Bioinformatic and experimental survey of 14-3-3-binding sites
Johnson, C., Crowther, S., Stafford, M. J., Campbell, D. G., Toth, R. L., & MacKintosh, C. (2010) · Biochemical Journal · doi:10.1042/bj20091834 · Cited by 337 · see citing works
Yes-associated protein (YAP) functions as a tumor suppressor in breast
Yuan, M., Tomlinson, V., Lara, R., Holliday, D. L., Chelala, C., Harada, T., Gangeswaran, R., Bishop, C. L., Smith, P., Danovi, S. A., et al. (2008) · Cell Death and Differentiation · doi:10.1038/cdd.2008.108 · Cited by 336 · see citing works
Self-citationJNK antagonizes Akt-mediated survival signals by phosphorylating 14-3-3
Sunayama, J., Tsuruta, F., Masuyama, N., & Gotoh, Y. (2005) · The Journal of Cell Biology · doi:10.1083/jcb.200409117 · Cited by 335 · see citing works
From Cell Structure to Transcription: Hippo Forges a New Path
Edgar, B. A. (2006) · Cell · doi:10.1016/j.cell.2006.01.005 · Cited by 331 · see citing works
The p53 family and programmed cell death
Pietsch, E. C., Sykes, S. M., McMahon, S. B., & Murphy, M. E. (2008) · Oncogene · doi:10.1038/onc.2008.315 · Cited by 314 · see citing works
Rescue of Hippo coactivator YAP1 triggers DNA damage–induced apoptosis in hematological cancers
Cottini, F., Hideshima, T., Xu, C., Sattler, M., Dori, M., Agnelli, L., ten Hacken, E., Bertilaccio, M. T. S., Antonini, E., Neri, A., et al. (2014) · Nature Medicine · doi:10.1038/nm.3562 · Cited by 310 · see citing works
Hippo Signaling in the Liver Regulates Organ Size, Cell Fate, and Carcinogenesis
Patel, S. H., Camargo, F. D., & Yimlamai, D. (2016) · Gastroenterology · doi:10.1053/j.gastro.2016.10.047 · Cited by 296 · see citing works
Akt1 in Endothelial Cell and Angiogenesis
Somanath, P. R., Razorenova, O. V., Chen, J., & Byzova, T. V. (2006) · Cell Cycle · doi:10.4161/cc.5.5.2538 · Cited by 298 · see citing works
Regulation of the Hippo-YAP Pathway by Glucose Sensor O-GlcNAcylation
Peng, C., Zhu, Y., Zhang, W., Liao, Q., Chen, Y., Zhao, X., Guo, Q., Shen, P., Zhen, B., Qian, X., et al. (2017) · Molecular Cell · doi:10.1016/j.molcel.2017.10.010 · Cited by 279 · see citing works
Mizuno, T., Murakami, H., Fujii, M., Ishiguro, F., Tanaka, I., Kondo, Y., Akatsuka, S., Toyokuni, S., Yokoi, K., Osada, H., et al. (2012) · Oncogene · doi:10.1038/onc.2012.5 · Cited by 279 · see citing works
Functional regulation of p73 and p63: development and cancer
Melino, G. (2003) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2003.10.004 · Cited by 277 · see citing works
Leong, C., Vidnovic, N., DeYoung, M. P., Sgroi, D. C., & Ellisen, L. W. (2007) · Journal of Clinical Investigation · doi:10.1172/jci30866 · Cited by 270 · see citing works
p63 and p73 in human cancer: defining the network
DeYoung, M. P., & Ellisen, L. W. (2007) · Oncogene · doi:10.1038/sj.onc.1210337 · Cited by 261 · see citing works
The LATS1 and LATS2 tumor suppressors: beyond the Hippo pathway
Furth, N., & Aylon, Y. (2017) · Cell Death and Differentiation · doi:10.1038/cdd.2017.99 · Cited by 262 · see citing works
Murakami, M., Nakagawa, M., Olson, E. N., & Nakagawa, O. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0509109102 · Cited by 261 · see citing works
PML, YAP, and p73 Are Components of a Proapoptotic Autoregulatory Feedback Loop
Lapi, E., Agostino, S. D., Donzelli, S., Gal, H., Domany, E., Rechavi, G., Pandolfi, P. P., Givol, D., Strano, S., Lü, X., et al. (2008) · Molecular Cell · doi:10.1016/j.molcel.2008.11.019 · Cited by 257 · see citing works
Emerging roles of TEAD transcription factors and its coactivators in cancers
Pobbati, A. V., & Hong, W. (2013) · Cancer Biology & Therapy · doi:10.4161/cbt.23788 · Cited by 256 · see citing works
Yes-associated protein regulates endothelial cell contact-mediated expression of angiopoietin-2
Choi, H.-J., Zhang, H., Park, H., Choi, K.-S., Lee, H., Agrawal, V., Kim, Y., & Kwon, Y. (2015) · Nature Communications · doi:10.1038/ncomms7943 · Cited by 247 · see citing works
Optogenetic control of cellular forces and mechanotransduction
Valon, L., Marín-Llauradó, A., Wyatt, T., Charras, G., & Trepat, X. (2017) · Nature Communications · doi:10.1038/ncomms14396 · Cited by 246 · see citing works
Targeting Akt in cancer for precision therapy
Hua, H. M., Zhang, H., Chen, J., Wang, J., Liu, J., & Jiang, Y. (2021) · Journal of Hematology & Oncology · doi:10.1186/s13045-021-01137-8 · Cited by 247 · see citing works
Multistep regulation of TFEB by MTORC1
Vega-Rubín-de-Celis, S., Peña-Llopis, S., Konda, M., & Brugarolas, J. (2017) · Autophagy · doi:10.1080/15548627.2016.1271514 · Cited by 215 · see citing works
p73 induction after DNA damage is regulated by checkpoint kinases Chk1 and Chk2Preprint
Urist, M. J., Tanaka, T., Poyurovsky, M. V., & Prives, C. L. (2004) · Genes & Development · doi:10.1101/gad.1221004 · Cited by 234 · see citing works
Marti, P., Stein, C., Blumer, T., Abraham, Y., Dill, M. T., Pikiolek, M., Orsini, V., Jurisic, G., Megel, P., Makowska, Z., et al. (2015) · Hepatology · doi:10.1002/hep.27992 · Cited by 232 · see citing works
Myocardial AKT: The Omnipresent Nexus
Sussman, M. A., Völkers, M., Fischer, K. M., Bailey, B., Cottage, C. T., Din, S., Gude, N. A., Avitabile, D., Alvarez, R., Sundararaman, B., et al. (2011) · Physiological Reviews · doi:10.1152/physrev.00024.2010 · Cited by 229 · see citing works
Verteporfin inhibits YAP function through up-regulating 14-3-3σ sequestering YAP in the cytoplasm.
Wang, C., Zhu, X., Feng, W., Yu, Y., Jeong, K., Guo, W., Lu, Y., & Mills, G. B. (2016) · Europe PMC (PubMed Central) · Cited by 228 · see citing works
Hiemer, S. E., Szymaniak, A. D., & Varelas, X. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.529115 · Cited by 227 · see citing works
Functional genomics of PCOS: from GWAS to molecular mechanisms
McAllister, J. M., Legro, R. S., Modi, B. P., & Strauss, J. F. (2015) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2014.12.004 · Cited by 220 · see citing works
p53-family proteins and their regulators: hubs and spokes in tumor suppression
Collavin, L., Lunardi, A., & Sal, G. D. (2010) · Cell Death and Differentiation · doi:10.1038/cdd.2010.35 · Cited by 219 · see citing works
PKB and the mitochondria: AKTing on apoptosis
Parcellier, A., Tintignac, L. A. J., Zhuravleva, E., & Hemmings, B. A. (2007) · Cellular Signalling · doi:10.1016/j.cellsig.2007.07.010 · Cited by 220 · see citing works
Agrin as a Mechanotransduction Signal Regulating YAP through the Hippo Pathway
Chakraborty, S., Njah, K., Pobbati, A. V., Lim, Y. B., Raju, A., Lakshmanan, M., Tergaonkar, V., Lim, C. T., & Hong, W. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.02.041 · Cited by 218 · see citing works
Oka, T., Remue, E., Meerschaert, K., Vanloo, B., Boucherie, C., Gfeller, D., Bader, G. D., Sidhu, S. S., Vandekerckhove, J. S., Gettemans, J., et al. (2010) · Biochemical Journal · doi:10.1042/bj20100870 · Cited by 213 · see citing works
Self-citationTamm, C., Böwer, N., & Annerén, C. (2011) · Journal of Cell Science · doi:10.1242/jcs.075796 · Cited by 216 · see citing works
Pungsrinont, T., Kallenbach, J., & Baniahmad, A. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms222011088 · Cited by 218 · see citing works
Mahoney, W. M., Jeong-Ho, H. O. N. G., Yaffe, M. B., & Farrance, I. K. G. (2005) · Biochemical Journal · doi:10.1042/bj20041434 · Cited by 212 · see citing works
Aqeilan, R. I., Donati, V. L., Palamarchuk, A., Trapasso, F., Kaou, M., Pekarsky, Y., Sudol, M., & Croce, C. M. (2005) · Cancer Research · doi:10.1158/0008-5472.can-05-1150 · Cited by 211 · see citing works
Self-citationThe Yes-associated protein 1 stabilizes p73 by preventing Itch-mediated ubiquitination of p73
Levy, D., Adamovich, Y., Reuven, N. B., & Shaul, Y. (2006) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4402063 · Cited by 210 · see citing works
Myc‐induced proliferation and transformation require Akt‐mediated phosphorylation of FoxO proteins
Bouchard, C., Marquardt, J., Brás, A., Medema, R. H., & Eilers, M. (2004) · The EMBO Journal · doi:10.1038/sj.emboj.7600279 · Cited by 211 · see citing works
Modena, P., Lualdi, E., Facchinetti, F., Veltman, J. A., Reid, J. F., Minardi, S. P., Janssen, I. M., Giangaspero, F., Forni, M., Finocchiaro, G., et al. (2006) · Journal of Clinical Oncology · doi:10.1200/jco.2006.06.3701 · Cited by 206 · see citing works
- Authors
- Basu, S., Totty, N. F., Irwin, M. S., Sudol, M., & Downward, J.
- Affiliations
- Cancer Research UK (GB)
- Hospital for Sick Children (CA)
- Icahn School of Medicine at Mount Sinai (US)
- Corresponding author
- Downward, Julian
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2003-01
- Volume
- 11
- Issue
- 1
- Pages
- 11-23
- ISSN
- 1097-2765 (ISSN-L)
- OpenAlex
- W2011818472
- Cited by
- 843
- References
- 41
- Citations by year
- 2026: 19 · 2025: 26 · 2024: 41 · 2023: 43 · 2022: 43 · 2021: 51 · 2020: 46 · 2019: 33 · 2018: 47 · 2017: 48 · 2016: 58 · 2015: 41 · 2014: 47 · 2013: 41 · 2012: 26
- FWCI
- 9.99
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Molecular Cell (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Cancer Research UK
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hippo pathway signaling and YAP/TAZ
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › 14-3-3 protein interactions
- Keywords
- Akt, YAP, protein phosphorylation, p73, apoptosis, DNA damage response, Bax expression, nuclear localization, transcriptional coactivation
- MeSH terms
- Tumor Protein p73, YAP-Signaling Proteins, Animals, Antibodies, Carrier Proteins, Cell Line, DNA-Binding Proteins, Fluorescent Dyes, Humans, Luminescent Proteins, Nuclear Proteins, Phosphoproteins, Phosphorylation, Protein Binding, Proto-Oncogene Proteins, Recombinant Fusion Proteins, Serine, Transcription Factors, Transcription, Genetic, Tyrosine 3-Monooxygenase, Genes, Tumor Suppressor, Apoptosis, Protein Serine-Threonine Kinases, Genes, Reporter, Amino Acid Motifs, Tumor Suppressor Proteins, RNA Interference, Adaptor Proteins, Signal Transducing, 14-3-3 Proteins, Green Fluorescent Proteins, Proto-Oncogene Proteins c-akt
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