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FoxO Proteins and Cardiac Pathology

  • Albert Wong
  • Elizabeth A. WoodcockEmail author
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 665)

Abstract

The FoxO family of transcription factors mediate a wide range of cellular responses from cell death to cell survival, growth inhibition and glucose utilization. This complex array of responses is regulated by an equally complex regulatory system, involving phosphorylation, ubiquitinization and acetylation, in addition to interactions with other transcription factors and transcriptional modifiers. In heart, FoxO proteins have been shown to be involved in development, in limiting hypertrophic growth responses and in cardioprotection provided by silent information regulator 1 (Sirt1). However, the range of responses mediated by FoxO proteins and the clear evidence for involvement of FoxO regulators in cardiac pathology, suggest that further pathological actions of FoxO family members remain to be elucidated.

Keywords

Cardiac Hypertrophy Serum Response Factor Cardiac Pathology cAMP Response Element Binding Protein Forkhead Transcription Factor 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    Burgering B. A brief introduction to FOXOlogy. Oncogene 2008; 27:2258–2262.PubMedCrossRefGoogle Scholar
  2. 2.
    Biggs WH 3rd, Cavenee WK, Arden KC. Identification and characterization of members of the FKHR (FOX O) subclass of winged-helix transcription factors in the mouse. Mamm Genome 2001; 12:416–25.PubMedCrossRefGoogle Scholar
  3. 3.
    Guarente L, Kenyon C. Genetic pathways that regulate ageing in model organisms. Nature 2000; 408:255–62.PubMedCrossRefGoogle Scholar
  4. 4.
    Richards JS, Sharma SC, Falender AE et al. Expression of FKHR, FKHRL1 and AFX genes in the rodent ovary: evidence for regulation by IGF-I, estrogen and the gonadotropins. Mol Endocrinol 2002; 16:580–99.PubMedCrossRefGoogle Scholar
  5. 5.
    Van der Heide LP, Jacobs FMJ, Burbach JPH et al. FoxO6 transcriptional activity is regulated by Thr(26) and Ser(184), independent of nucleo-cytoplasmic shuttling. Biochem J 2005; 391:623–629.PubMedCrossRefGoogle Scholar
  6. 6.
    Morris JB, Kenney B, Huynh H et al. Regulation of the proapoptotic factor FOXO1 (FKHR) in cardiomyocytes by growth factors and α1-adrenergic agonists. Endocrinology 2005; 146:4370–6.PubMedCrossRefGoogle Scholar
  7. 7.
    Burgering BM, Kops GJ. Cell cycle and death control: long live Forkheads. Trends Biochem Sci 2002; 27:352–60.PubMedCrossRefGoogle Scholar
  8. 8.
    Moylan JS, Smith JD, Chambers MA et al. TNF induction of atrogin-1/MAFbx mRNA depends on Foxo4 expression but not AKT-Foxol/3 signaling. Am J Physiol 2008; 295:C986–993.CrossRefGoogle Scholar
  9. 9.
    van der Vos KE, Coffer PJ. FOXO-binding partners: it takes two to tango. Oncogene 2008; 27:2289–2299.PubMedCrossRefGoogle Scholar
  10. 10.
    Alcendor RR, Gao SM, Zhai PY et al. Sirtl regulates aging and resistance to oxidative stress in the heart. Circ Res 2007; 100:1512–1521.PubMedCrossRefGoogle Scholar
  11. 11.
    Accili D, Arden KC. FoxOs at the crossroads of cellular metabolism, differentiation and transformation. Cell 2004; 117:421–6.PubMedCrossRefGoogle Scholar
  12. 12.
    Brunet A. The multiple roles of FOXO transcription factors. M S-Medicine Sciences 2004; 20:856–859.Google Scholar
  13. 13.
    Jonsson H, Peng SL. Forkhead transcription factors in immunology. Cell Mol Life Sci 2005; 62:397–409.PubMedCrossRefGoogle Scholar
  14. 14.
    Lam EWF, Francis RE, Petkovic M. FOXO transcription factors: key regulators of cell fate. Biochem Soc Trans 2006; 34:722–726.PubMedCrossRefGoogle Scholar
  15. 15.
    Lehtinen MK, Yuan ZQ, Boag PR et al. A conserved MST-FOXO signaling pathway mediates oxidative-stress responses and extends life span. Cell 2006; 125:987–1001.PubMedCrossRefGoogle Scholar
  16. 16.
    Kobayashi Y, Furukawa-Hibi Y, Chen C et al. SIRT1 is critical regulator of FOXO-mediated transcription in response to oxidative stress. Int J Mol Med 2005; 16:237–243.PubMedGoogle Scholar
  17. 17.
    Fu Z, Tindall DJ. FOXOs, cancer and regulation of apoptosis. Oncogene 2008; 27:2312–2319.PubMedCrossRefGoogle Scholar
  18. 18.
    Yan L, Lavin VA, Moser LR et al. PP2A Regulates the Pro-apoptotic Activity of FOXO1. J Biol Chem 2008; 283:7411–20.PubMedCrossRefGoogle Scholar
  19. 19.
    Urbich C, Knau A, Fichtlscherer S et al. FOXO-dependent expression of the proapoptotic protein Bim: pivotal role for apoptosis signaling in endothelial progenitor cells. FASEB J 2005; 19:974–6.PubMedGoogle Scholar
  20. 20.
    Tran H, Brunet A, Grenier JM et al. DNA repair pathway stimulated by the forkhead transcription factor FOXO3a through the Gadd45 protein. Science 2002; 296:530–4.PubMedCrossRefGoogle Scholar
  21. 21.
    Stahl M, Dijkers PF, Kops GJ et al. The forkhead transcription factor FoxO regulates transcription of p27Kip1 and Bim in response to IL-2. J Immunol 2002; 168:5024–31.PubMedGoogle Scholar
  22. 22.
    Kuiperij HB, van der Horst A, Raaijmakers J et al. Activation of FoxO transcription factors contributes to the antiproliferative effect of cAMP. Oncogene 2005; 24:2087–95.PubMedCrossRefGoogle Scholar
  23. 23.
    Kops GJ, Medema RH, Glassford J et al. Control of cell cycleexit and entry by protein kinase B-regulated forkhead transcription factors. Mol Cell Biol 2002; 22:2025–36.PubMedCrossRefGoogle Scholar
  24. 24.
    Barthel A, Schmoll D, Unterman TG. FoxO proteins in insulin action and metabolism. Trend Endocrinol Metab 2005; 16:183–189.CrossRefGoogle Scholar
  25. 25.
    Nakae J, Oki M, Cao YH. The FoxO transcription factors and metabolic regulation. FEBS Lett 2008; 582:54–67.PubMedCrossRefGoogle Scholar
  26. 26.
    Gross DN, van den Heuvel APJ, Birnbaum MJ. The role of FoxO in the regulation of metabolism. Oncogene 2008; 27:2320–2336.PubMedCrossRefGoogle Scholar
  27. 27.
    Zhang WW, Patil S, Chauhan B et al. FoxO1 regulates multiple metabolic pathways in the liver-Effects on gluconeogenic, glycolytic and lipogenic gene expression. J Biol Chem 2006; 281:10105–10117.PubMedCrossRefGoogle Scholar
  28. 28.
    Tang ED, Nunez G, Barr FG et al. Negative regulation of the forkhead transcription factor FKHR by Akt. J Biol Chem 1999; 274:16741–6.PubMedCrossRefGoogle Scholar
  29. 29.
    Chan TO, Rittenhouse SE, Tsichlis PN. AKT/PKB and other D3 phosphoinositide-regulated kinases: Kinase activation by phosphoinositide-dependent phosphorylation. Annu Rev Biochem 1999; 68:965–1014.PubMedCrossRefGoogle Scholar
  30. 30.
    Brunet A, Bonni A, Zigmond MJ et al. Akt promotes cell survival by phosphorylating and inhibiting a Forkhead transcription factor. Cell 1999; 96:857–68.PubMedCrossRefGoogle Scholar
  31. 31.
    Nakae J, Barr V, Accili D. Differential regulation of gene expression by insulin and IGF-1 receptors correlates with phosphorylation of a single amino acid residue in the forkhead transcription factor FKHR. EMBO J 2000; 19:989–96.PubMedCrossRefGoogle Scholar
  32. 32.
    Zhang X, Gan L, Pan H et al. Phosphorylation of serine 256 suppresses transactivation by FKHR (FOXO1) by multiple mechanisms. Direct and indirect effects on nuclear/cytoplasmic shuttling and DNA binding. J Biol Chem 2002; 277:45276–84.PubMedCrossRefGoogle Scholar
  33. 33.
    Obsil T, Ghirlando R, Anderson DE et al. Two 14-3-3 binding motifs are required for stable association of forkhead transcription factor FOXO4 with 14-3-3 proteins and inhibition of DNA binding. Biochemistry 2003; 42:15264–15272.PubMedCrossRefGoogle Scholar
  34. 34.
    Pombo CM, Bonventre JY, Molnar A et al. Activation of a human Ste20-like kinase by oxidant stress defines a novel stress response pathway. EMBO J 1996; 15:4537–46.PubMedGoogle Scholar
  35. 35.
    Feig LA, Buchsbaum RJ. Cell signaling: life or death decisions of ras proteins. Curr Biol 2002; 12:R259–61.PubMedCrossRefGoogle Scholar
  36. 36.
    Komatsu D, Kato M, Nakayama J et al. NADPH oxidase 1 plays a critical mediating role in oncogenic Ras-induced vascular endothelial growth factor expression. Oncogene 2008; 27:4724–32.PubMedCrossRefGoogle Scholar
  37. 37.
    Song JJ, Lee YJ. Differential cleavageofMst1 by caspase-7/−3 is responsible for TRAIL-induced activation of the MAPK superfamily. Cell Signal 2008; 20:892–906.PubMedCrossRefGoogle Scholar
  38. 38.
    Anand R, Kim AY, Brent M et al. Biochemical analysis of MST1 kinase: Elucidation of a C-terminal regulatory region. Biochemistry 2008; 47:6719–6726.PubMedCrossRefGoogle Scholar
  39. 39.
    Brent MM, Anand R, Marmorstein R. Structural basis for DNA recognition by FoxO1 and its regulation by posttranslational modification. Structure 2008; 16:1407–16.PubMedCrossRefGoogle Scholar
  40. 40.
    Matsuzaki H, Daitoku H, Hatta M et al. Insulin-induced phosphorylation of FKHR (Foxo1) targets to proteasomal degradation. Proc Natl Acad Sci USA 2003; 100:11285–90.PubMedCrossRefGoogle Scholar
  41. 41.
    Dehan E, Pagano M. Skp2, the FoxO1 hunter. Cancer Cell 2005; 7:209–210.PubMedCrossRefGoogle Scholar
  42. 42.
    Li HH, Willis MS, Lockyer P et al. Atrogin-1 inhibits Akt-dependent cardiac hypertrophy in mice via ubiquitin-dependent coactivation of Forkhead proteins. J Clin Invest 2007; 117:3211–3223.PubMedCrossRefGoogle Scholar
  43. 43.
    van der Horst A, de Vries-Smits AM, Brenkman AB et al. FOXO4 transcriptional activity is regulated by monoubiquitination and USP7/HAUSP. Nat Cell Biol 2006; 8:1064–73.PubMedCrossRefGoogle Scholar
  44. 44.
    Matsuzaki H, Daitoku H, Hatta M et al. Acetylation of Foxol alters its DNA-binding ability and sensitivity to phosphorylation. Proc Natl Acad Sci USA 2005; 102:11278–11283.PubMedCrossRefGoogle Scholar
  45. 45.
    Yang YH, Hou HY, Haller EM et al. Suppression of FOXO1 activity by FHL2 through SIRT1-mediated deacetylation. EMBO Journal 2005; 24:1021–1032.PubMedCrossRefGoogle Scholar
  46. 46.
    Motta MC, Divecha N, Lemieux M et al. Mammalian SIRT1 represses forkhead transcription factors. Cell 2004; 116:551–63.PubMedCrossRefGoogle Scholar
  47. 47.
    Gomis RR, Alarcon C, He W et al. A FoxO-Smad synexpression group in human keratinocytes. Proc Natl Acad Sci USA 2006; 103:12747–52.PubMedCrossRefGoogle Scholar
  48. 48.
    Liu ZP, Wang Z, Yanagisawa H et al. Phenotypic modulation of smooth muscle cells through interaction of FoxO4 and myocardin. Dev Cell 2005; 9:261–70.PubMedCrossRefGoogle Scholar
  49. 49.
    Essers MAG, de Vries-Smits LMM, Barker N et al. Functional interaction between β-catenin and FOXO in oxidative stress signaling. Science 2005; 308:1181–1184.PubMedCrossRefGoogle Scholar
  50. 50.
    Yue TL, Bao W, Jucker BM et al. Activation of peroxisome proliferaror-activated receptor-α protects the heart from ischemia/reperfusion injury. Circulation 2003; 108:2393–2399.PubMedCrossRefGoogle Scholar
  51. 51.
    Cao Z, Ye P, Long C et al. Effect of pioglitazone, a peroxisome proliferator-activared receptor γ agonist, on ischemia-reperfusion injury in rats. Pharmacology 2007; 79:184–92.PubMedCrossRefGoogle Scholar
  52. 52.
    Puigserver P, Rhee J, Donovan J et al. Insulin-regulated hepatic gluconeogenesis through FOXOI-PGC-1α interaction. Nature 2003; 423:550–5.PubMedCrossRefGoogle Scholar
  53. 53.
    Cen B, Selvaraj A, Prywes R. Myocardin/MKL family of SRF coactivators: Key regulators of immediate early and muscle specific gene expression. J Cell Biochem 2004; 93:74–82.PubMedCrossRefGoogle Scholar
  54. 54.
    Arden KC, Fox O: linking new signaling pathways. Mol Cell 2004; 14:416–8.PubMedCrossRefGoogle Scholar
  55. 55.
    Arce L, Yokoyama NN, Waterman ML. Diversity of LEFITCF action in development and disease. Oncogene 2006; 25:7492–504.PubMedCrossRefGoogle Scholar
  56. 56.
    Lanzafame AA, Turnbull L, Amiramahdi F et al. Inositol phospholipids localized to caveolae in rat heart are regulated by aI-adrenergic receptors and by ischemia-reperfusion. Am J Physiol 2006; 290:H2059–65.Google Scholar
  57. 57.
    Woodcock E, Lambert K, Phan T et al. Inositol phosphate metabolism during myocardial ischemia. J Mol Cell Cardiol 1997; 29:449–460.PubMedCrossRefGoogle Scholar
  58. 58.
    Amirahmadi F, Turnbull L, Du XJ et al. Heightened α1A-adrenergic receptor activity suppresses ischaemia/ reperfusion-induced Ins(1,4,5)P3 generation in the mouse heart: a comparison with ischaemic preconditioning. Clin Sci (Lond) 2008; 114:157–64.CrossRefGoogle Scholar
  59. 59.
    Thandroyen F, McCarthy J, Burton K et al. Ryanodine and caffeine prevent ventricular arrhythmias during acute myocardial ischemia and reperfusion in rat heart. Circ Res 1988; 62:306–314.PubMedGoogle Scholar
  60. 60.
    Heidbuchel H, Tack J, Vanneste L et al. Significance of arrhythmias during the first 24 hours of acute myocardial infarction treated with alteplase and effect of early administration of a β-blocker or a bradycardiac agent on their incidence. Circulation 1994; 89:1051–1059.PubMedGoogle Scholar
  61. 61.
    Kopecky SL, Aviles RJ, Bell MR et al. A randomized, double-blinded, placebo-controlled, dose-ranging study measuring the effect of an adenosine agonist on infarct size reduction in patients undergoing primary percutaneous transluminal coronary angioplasty: the ADMIRE (AmP579 Delivery for Myocardial Infarction REduction) study. Am Heart J 2003; 146:146–52.PubMedCrossRefGoogle Scholar
  62. 62.
    Gottlieb RA, Burleson KO, Kloner RA et al. Reperfusion injury induces apoptosis in rabbit cardiomyocytes, J Clin Invest 1994; 94:1621–1628.PubMedCrossRefGoogle Scholar
  63. 63.
    Elsasser A, Suzuki K, Schaper J. Unresolved issues regarding the role of apoptosis in the pathogenesis of ischemic injury and heart failure. J Mol Cell Cardiol 2000; 32:711–24.PubMedCrossRefGoogle Scholar
  64. 64.
    Fujio Y, Nguyen T, Wencker D et al. Akt promotes survival of cardiornyocytes in vitro and protects against ischemia-reperfusion injury in mouse heart. Circulation 2000; 101:660–667.PubMedGoogle Scholar
  65. 65.
    Matsui T, Tao JZ, delMonte F et al. Akt activation preserves cardiac function and prevents injury after transient cardiac ischemia in vivo. Circulation 2001; 104:330–335.PubMedGoogle Scholar
  66. 66.
    Matsui T, Rosenzweig A. Convergent signal transduction pathways controlling cardiomyocyte survival and function: the role of PI 3-kinase and Akt. J Mol Cell Cardiol 2005; 38:63–71.PubMedCrossRefGoogle Scholar
  67. 67.
    Modur V, Nagarajan R, Evers BM et al. FOXO proteins regulate tumor necrosis factor-related apoptosis inducing ligand expression. Implications for PTEN mutation in prostate cancer. J Biol Chem 2002; 277:47928–37.PubMedCrossRefGoogle Scholar
  68. 68.
    Ciechomska I, Pyrzynska B, Kazmierczak P et al. Inhibition of Akr kinase signalling and activation of Forkhead are indispensable for upregulation of FasL expression in apoptosis of glioma cells. Oncogene 2003; 22:7617–7627.PubMedCrossRefGoogle Scholar
  69. 69.
    Sunters A, de Mattos SF, Stahl M et al. Fox03a transcriptional regulation of bim controls apoptosis in paclitaxekreated breast cancer cell lines. J Biol Chem 2003; 278:49795–49805.PubMedCrossRefGoogle Scholar
  70. 70.
    Kitsis RN, Mann DL. Apoptosis and the heart: a decade of progress. J Mol Cell Cardiol 2005; 38:1–2.PubMedCrossRefGoogle Scholar
  71. 71.
    Bahi N, Zhang J, Llovera M et al. Switch from caspase-dependent to caspase-independent death during heart development: essential role of endonuclease G in ischemia-induced DNA processing of differentiated cardiomyocytes. J Biol Chem 2006; 281:22943–52.PubMedCrossRefGoogle Scholar
  72. 72.
    Tanaka M, Ito H, Akimoto S et al. Hypoxia induces apoptosis with enhanced expression of Fas antigen messenger RNA in cultured neonatal rat cardiomyocytes. Circ Res 1994; 75:426–433.PubMedGoogle Scholar
  73. 73.
    Stephanou A, Scarabelli TM, Brar BK et al. Induction of apoptosis and Fas receptor/Fas ligand expression by ischemia/reperfusion in cardiac myocytes requires serine 727 of the STAT-1 transcription factor but not tyrosine 701. J Biol Chem 2001; 276:28340–28347.PubMedCrossRefGoogle Scholar
  74. 74.
    Adams JW, Pagel AL, Means CK et al. Cardiomyocyte apoptosis induced by Gαq signaling is mediated by permeability transition pore formation and activation of the mitochondrial death pathway. Circ Res 2000; 87:1180–1187.PubMedGoogle Scholar
  75. 75.
    Yamamoto S, Yang G, Zablocki D et al. Activation of Mst1 causes dilated cardiomyopathy by stimulating apoptosis without compensatory ventricular myocyte hypertrophy. J Clin Invest 2003; 111:1463–74.PubMedGoogle Scholar
  76. 76.
    Odashima M, Usui S, Takagi H et al. Inhibition of endogenous Mst1 prevents apoptosis and cardiac dysfunction without affecting cardiac hypertrophy after myocardial infarction. Circ Res 2007;May 11;100(9):1344–52.PubMedCrossRefGoogle Scholar
  77. 77.
    Skurk C, Izumiya Y, Maatz H et al. The FOXO3a transcription factor regulates cardiac myocyte size downstream of AKT signaling. J Biol Chem 2005; May 27;280(21):20814–23PubMedCrossRefGoogle Scholar
  78. 78.
    Rokudai S, Fujita N, Kitahara O et al. Involvement of FKHR-dependent TRADD expression in chemotherapeutic drug-induced apoptosis. Mol Cell Biol 2002; 22:8695–708.PubMedCrossRefGoogle Scholar
  79. 79.
    Zhao J, Brault JJ, Schild A et al. FoxO3 coordinately activates protein degradation by the autophagic/lysosomal and proteasomal pathways in atrophying muscle cells. Cell Metab 2007; 6:472–483.PubMedCrossRefGoogle Scholar
  80. 80.
    Salih DAM, Brunet A. FoxO transcription factors in the maintenance of cellular homeostasis during aging. Curr Opin Cell Biol 2008; 20:126–136.PubMedCrossRefGoogle Scholar
  81. 81.
    Fukuoka M, Daitoku H, Hatta M et al. Negative regulation of forkhead transcription factor AFX (Foxo4) by CBP-induced acetylation. Int J Mol Med 2003; 12:503–8.PubMedGoogle Scholar
  82. 82.
    Daitoku H, Hatta M, Matsuzaki H et al. Silent information regulator 2 potentiates Foxol-mediated transcription through its deacetylase activity. Proc Natl Acad Sci USA 2004; 101:10042–7.PubMedCrossRefGoogle Scholar
  83. 83.
    Alcendor RR, Kirshenbaum LA, Imai S et al. Silent information regulator 2a, a longevity factor and class III histone deacetylase, is an essential endogenous apoptosis inhibitor in cardiac myocytes. Circ Res 2004; 95:971–80.PubMedCrossRefGoogle Scholar
  84. 84.
    Brunet A, Sweeney LB, Sturgill JF et al. Stress-dependent regulation of FOXO transcription factors by the SIRT1 deacetylase. Science 2004; 303:2011–5.PubMedCrossRefGoogle Scholar
  85. 85.
    Giannakou ME, Partridge L. The interaction between FOXO and SIRT1: tipping the balance towards survival. Trend Cell Biol 2004; 14:408–412.CrossRefGoogle Scholar
  86. 86.
    Toth A, Nickson P, Qin LL et al. Differential regulation of cardiomyocyte survival and hypertrophy by MDM2, an E3 ubiquitin ligase. J Biol Chem 2006; 281:3679–89.PubMedCrossRefGoogle Scholar
  87. 87.
    Hahn JY, Cho HJ, Bae JW et al. β-Catenin overexpression reduces myocardial infarct size through differential effects on cardiomyocytes and cardiac fibroblasts. J Biol Chem 2006; 281:30979–89.PubMedCrossRefGoogle Scholar
  88. 88.
    Baurand A, Zelarayan L, Betney R et al. β-Catenin downregulation is required for adaptive cardiac remodeling. Circ Res 2007; May 11;100(9):1353–62.PubMedCrossRefGoogle Scholar
  89. 89.
    Almeida M, Han L, Martin-Millan M et al. Oxidative stress antagonizes Wnt signaling in osteoblast precursors by diverting β-catenin from T-cell factor-to forkhead box O-mediated transcription. J Biol Chem 2007; 282:27298–305.PubMedCrossRefGoogle Scholar
  90. 90.
    McMullen JR, Shioi T, Zhang L et al. Phosphoinositide 3-kinase(p110α) plays a critical role for the induction of physiological, but not pathological, cardiac hypertrophy. Proc Natl Acad Sci USA 2003; 100:12355–12360.PubMedCrossRefGoogle Scholar
  91. 91.
    Lorell B. Transition from hypertrophy to failure. Circulation 1997; 96:3824–3827.PubMedGoogle Scholar
  92. 92.
    Tardiff JC. Cardiac hypertrophy: stressing out the heart. J Clin Invest 2006; 116:1467–1470.PubMedCrossRefGoogle Scholar
  93. 93.
    Ni YG, Berenji K, Wang N et al. Foxo transcription factors blunt cardiac hypertrophy by inhibiting calcineurin signaling. Circulation 2006; 114:1159–68.PubMedCrossRefGoogle Scholar
  94. 94.
    Fang CX, Dong F, Thomas DP et al. Hypertrophic cardiomyopathy in high-fat diet-induced obesity: role of suppression of forkhead transcription factor and atrophy gene transcription. Am J Physiol 2008; 295:H1206–H1215.Google Scholar
  95. 95.
    McMullen JR, Amirahmadi F, Woodcock EA et al. Protective effects of exercise and phosphoinositide 3-kinase(p110α) signaling in dilated and hypertrophic cardiomyopathy. Proc Natl Acad Sci USA 2007; 104:612–617.PubMedCrossRefGoogle Scholar
  96. 96.
    Hauck L, Harms C, Grothe D et al. Critical role for Fox03a-dependent regulation of p21(CIPl)/ (WAF1) in response to statin signaling in cardiac myocytes. Circ Res 2007; 100:50–60.PubMedCrossRefGoogle Scholar
  97. 97.
    Xing W, Zhang TC, Cao D et al. Myocardin induces cardiomyocyte hypertrophy. Circ Res 2006; Apr 28;98(8):1089–97.PubMedCrossRefGoogle Scholar
  98. 98.
    Evans-Anderson HJ, Alfieri CM, Yutzey KE. Regulation of cardiomyocyte proliferation and myocardial growth during development by FOXO transcription factors. Circ Res 2008; Mar 28;102(6):686–94.PubMedCrossRefGoogle Scholar
  99. 99.
    Hosaka T, Biggs WH, Tieu D et al. Disruption of forkhead transcription factor (FOXO) family members in mice reveals their functional diversification. Proc Natl Acad Sci USA 2004; 101:2975–2980.PubMedCrossRefGoogle Scholar
  100. 100.
    Small EM, Warkman AS, Wang DZ et al. Myocardin is sufficient and necessary for cardiac gene expression in Xenopus. Development 2005; 132:987–997.PubMedCrossRefGoogle Scholar
  101. 101.
    Creemers EE, Sutherland LB, McAnally J et al. Myocardin is a direct transcriptional target of Mef2, Tead and Foxo proteins during cardiovascular development. Development 2006; 133:4245–4256.PubMedCrossRefGoogle Scholar

Copyright information

© Landes Bioscience and Springer+Business Media 2009

Authors and Affiliations

  1. 1.Molecular Cardiology LaboratoryBaker IDI Heart and Diabetes InstituteMelbourneAustralia
  2. 2.Department of Biochemistry and Molecular BiologyMonash UniversityClaytonAustralia

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