Interplay of dFOXO and Two ETS-Family Transcription Factors Determines Lifespan in

English version České info

Despite the apparent complexity of ageing, animal lifespan can be extended. Activity of Forkhead Box O (FoxO) transcription factors can prolong survival of organisms ranging from the budding yeast to the fruit fly, and FoxO gene variants are linked to human longevity. FoxOs extend lifespan by driving complex, widespread changes in gene expression. Their primary targets include a second tier of transcriptional regulators, but it remains unclear how these secondary regulators are involved in the anti-ageing programmes orchestrated by FoxOs in vivo. To elucidate the role of this second tier, we identify a transcription factor called Anterior open (Aop) as directly regulated by the single Drosophila melanogaster FoxO protein (dFOXO) in the adult fly gut. Under certain circumstances, such as co-activation of the Pointed (PNT) transcription factor, dFOXO can be detrimental to lifespan. The role of Aop is to protect from this negative synergistic effect. Additionally, activation of AOP in the fly adipose tissue can robustly extend lifespan. Our study reveals a complex interplay between two evolutionarily conserved transcriptional regulators and dFOXO in lifespan. This significance of this interplay may extend to other physiological processes where these transcription factors play important roles.

Vyšlo v časopise: Interplay of dFOXO and Two ETS-Family Transcription Factors Determines Lifespan in. PLoS Genet 10(9): e32767. doi:10.1371/journal.pgen.1004619
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004619

Souhrn

Zdroje

1. GiannakouME, GossM, JungerMA, HafenE, LeeversSJ, et al. (2004) Long-lived Drosophila with overexpressed dFOXO in adult fat body. Science 305: 361.

2. HwangboDS, GershmanB, TuMP, PalmerM, TatarM (2004) Drosophila dFOXO controls lifespan and regulates insulin signalling in brain and fat body. Nature 429: 562–566.

3. DemontisF, PerrimonN (2010) FOXO/4E-BP signaling in Drosophila muscles regulates organism-wide proteostasis during aging. Cell 143: 813–825.

4. AlicN, TulletJ, NiccoliT, BroughtonS, HoddinottMP, et al. (2014) Cell-nonautonomous effects of dFOXO/DAF-16 in ageing. Cell Rep 6: 608–616.

5. KenyonC, ChangJ, GenschE, RudnerA, TabtiangR (1993) A C. elegans mutant that lives twice as long as wild type. Nature 366: 461–464.

6. SlackC, GiannakouME, FoleyA, GossM, PartridgeL (2011) dFOXO-independent effects of reduced insulin-like signaling in Drosophila. Aging Cell 10: 735–748.

7. PostnikoffSD, MaloME, WongB, HarknessTA (2012) The yeast forkhead transcription factors fkh1 and fkh2 regulate lifespan and stress response together with the anaphase-promoting complex. PLoS Genet 8: e1002583.

8. KuningasM, MagiR, WestendorpRG, SlagboomPE, RemmM, et al. (2007) Haplotypes in the human Foxo1a and Foxo3a genes; impact on disease and mortality at old age. Eur J Hum Genet 15: 294–301.

9. WillcoxBJ, DonlonTA, HeQ, ChenR, GroveJS, et al. (2008) FOXO3A genotype is strongly associated with human longevity. Proc Natl Acad Sci U S A 105: 13987–13992.

10. FlachsbartF, CaliebeA, KleindorpR, BlancheH, von Eller-EbersteinH, et al. (2009) Association of FOXO3A variation with human longevity confirmed in German centenarians. Proc Natl Acad Sci U S A 106: 2700–2705.

11. AnselmiCV, MaloviniA, RoncaratiR, NovelliV, VillaF, et al. (2009) Association of the FOXO3A locus with extreme longevity in a southern Italian centenarian study. Rejuvenation Res 12: 95–104.

12. PawlikowskaL, HuD, HuntsmanS, SungA, ChuC, et al. (2009) Association of common genetic variation in the insulin/IGF1 signaling pathway with human longevity. Aging Cell 8: 460–472.

13. EijkelenboomA, BurgeringBM (2013) FOXOs: signalling integrators for homeostasis maintenance. Nat Rev Mol Cell Biol 14: 83–97.

14. MurphyCT, McCarrollSA, BargmannCI, FraserA, KamathRS, et al. (2003) Genes that act downstream of DAF-16 to influence the lifespan of Caenorhabditis elegans. Nature 424: 277–283.

15. McElweeJJ, SchusterE, BlancE, PiperMD, ThomasJH, et al. (2007) Evolutionary conservation of regulated longevity assurance mechanisms. Genome Biol 8: R132.

16. SchusterE, McElweeJJ, TulletJM, DoonanR, MatthijssensF, et al. (2010) DamID in C. elegans reveals longevity-associated targets of DAF-16/FoxO. Mol Syst Biol 6: 399.

17. AlicN, AndrewsTD, GiannakouME, PapatheodorouI, SlackC, et al. (2011) Genome-wide dFOXO targets and topology of the transcriptomic response to stress and insulin signalling. Mol Syst Biol 7: 502.

18. BaiH, PingK, HernandezAM, TatarM (2013) Activin Signaling Targeted by Insulin/dFOXO Regulates Aging and Muscle Proteostasis in Drosophila. PLoS Genet 9 (11) e1003941.

19. WebbAE, PollinaEA, VierbuchenT, UrbanN, UcarD, et al. (2013) FOXO3 shares common targets with ASCL1 genome-wide and inhibits ASCL1-dependent neurogenesis. Cell Rep 4: 477–491.

20. EijkelenboomA, MokryM, de WitE, SmitsLM, PoldermanPE, et al. (2013) Genome-wide analysis of FOXO3 mediated transcription regulation through RNA polymerase II profiling. Mol Syst Biol 9: 638.

21. PuigO, TjianR (2005) Transcriptional feedback control of insulin receptor by dFOXO/FOXO1. Genes Dev 19: 2435–2446.

22. van der VosKE, CofferPJ (2008) FOXO-binding partners: it takes two to tango. Oncogene 27: 2289–2299.

23. BouchardC, MarquardtJ, BrasA, MedemaRH, EilersM (2004) Myc-induced proliferation and transformation require Akt-mediated phosphorylation of FoxO proteins. EMBO J 23: 2830–2840.

24. NemotoS, FergussonMM, FinkelT (2004) Nutrient availability regulates SIRT1 through a forkhead-dependent pathway. Science 306: 2105–2108.

25. OggS, ParadisS, GottliebS, PattersonGI, LeeL, et al. (1997) The Fork head transcription factor DAF-16 transduces insulin-like metabolic and longevity signals in C. elegans. Nature 389: 994–999.

26. SeoaneJ, LeHV, ShenL, AndersonSA, MassagueJ (2004) Integration of Smad and forkhead pathways in the control of neuroepithelial and glioblastoma cell proliferation. Cell 117: 211–223.

27. EssersMA, de Vries-SmitsLM, BarkerN, PoldermanPE, BurgeringBM, et al. (2005) Functional interaction between beta-catenin and FOXO in oxidative stress signaling. Science 308: 1181–1184.

28. TelemanAA, HietakangasV, SayadianAC, CohenSM (2008) Nutritional control of protein biosynthetic capacity by insulin via Myc in Drosophila. Cell Metab 7: 21–32.

29. PaikJH, KolliparaR, ChuG, JiH, XiaoY, et al. (2007) FoxOs are lineage-restricted redundant tumor suppressors and regulate endothelial cell homeostasis. Cell 128: 309–323.

30. TothovaZ, KolliparaR, HuntlyBJ, LeeBH, CastrillonDH, et al. (2007) FoxOs are critical mediators of hematopoietic stem cell resistance to physiologic oxidative stress. Cell 128: 325–339.

31. PoirierL, ShaneA, ZhengJ, SeroudeL (2008) Characterization of the Drosophila gene-switch system in aging studies: a cautionary tale. Aging Cell 7: 758–770.

32. GiannakouME, GossM, JacobsonJ, VintiG, LeeversSJ, et al. (2007) Dynamics of the action of dFOXO on adult mortality in Drosophila. Aging Cell 6: 429–438.

33. GiannakouME, GossM, PartridgeL (2008) Role of dFOXO in lifespan extension by dietary restriction in Drosophila melanogaster: not required, but its activity modulates the response. Aging Cell 7: 187–198.

34. MinKJ, YamamotoR, BuchS, PankratzM, TatarM (2008) Drosophila lifespan control by dietary restriction independent of insulin-like signaling. Aging Cell 7: 199–206.

35. LibinaN, BermanJR, KenyonC (2003) Tissue-specific activities of C. elegans DAF-16 in the regulation of lifespan. Cell 115: 489–502.

36. BluherM, KahnBB, KahnCR (2003) Extended longevity in mice lacking the insulin receptor in adipose tissue. Science 299: 572–574.

37. PuigO, MarrMT, RuhfML, TjianR (2003) Control of cell number by Drosophila FOXO: downstream and feedback regulation of the insulin receptor pathway. Genes Dev 17: 2006–2020.

38. JungerMA, RintelenF, StockerH, WassermanJD, VeghM, et al. (2003) The Drosophila forkhead transcription factor FOXO mediates the reduction in cell number associated with reduced insulin signaling. J Biol 2: 20.

39. KarpacJ, BiteauB, JasperH (2013) Misregulation of an adaptive metabolic response contributes to the age-related disruption of lipid homeostasis in Drosophila. Cell Rep 4: 1250–1261.

40. BreslinT, EdenP, KroghM (2004) Comparing functional annotation analyses with Catmap. BMC Bioinformatics 5: 193.

41. BahadoraniS, ChoJ, LoT, ContrerasH, LawalHO, et al. (2010) Neuronal expression of a single-subunit yeast NADH-ubiquinone oxidoreductase (Ndi1) extends Drosophila lifespan. Aging Cell 9: 191–202.

42. SanzA, SoikkeliM, Portero-OtinM, WilsonA, KemppainenE, et al. (2010) Expression of the yeast NADH dehydrogenase Ndi1 in Drosophila confers increased lifespan independently of dietary restriction. Proc Natl Acad Sci U S A 107: 9105–9110.

43. Casas-TintoS, MarrMT2nd, AndreuP, PuigO (2007) Characterization of the Drosophila insulin receptor promoter. Biochim Biophys Acta 1769: 236–243.

44. RoukensMG, Alloul-RamdhaniM, MoghadasiS, Op den BrouwM, BakerDA (2008) Downregulation of vertebrate Tel (ETV6) and Drosophila Yan is facilitated by an evolutionarily conserved mechanism of F-box-mediated ubiquitination. Mol Cell Biol 28: 4394–4406.

45. RoukensMG, Alloul-RamdhaniM, BaanB, KobayashiK, Peterson-MaduroJ, et al. (2010) Control of endothelial sprouting by a Tel-CtBP complex. Nat Cell Biol 12: 933–942.

46. HockH, MeadeE, MedeirosS, SchindlerJW, ValkPJ, et al. (2004) Tel/Etv6 is an essential and selective regulator of adult hematopoietic stem cell survival. Genes Dev 18: 2336–2341.

47. LaiZC, RubinGM (1992) Negative control of photoreceptor development in Drosophila by the product of the yan gene, an ETS domain protein. Cell 70: 609–620.

48. RebayI, RubinGM (1995) Yan functions as a general inhibitor of differentiation and is negatively regulated by activation of the Ras1/MAPK pathway. Cell 81: 857–866.

49. NiJQ, ZhouR, CzechB, LiuLP, HolderbaumL, et al. (2011) A genome-scale shRNA resource for transgenic RNAi in Drosophila. Nat Methods 8: 405–407.

50. CoxDR (1972) Regression models and life-tables. J R Stat Soc Ser B Stat Methodol 34: 187–220.

51. O'NeillEM, RebayI, TjianR, RubinGM (1994) The activities of two Ets-related transcription factors required for Drosophila eye development are modulated by the Ras/MAPK pathway. Cell 78: 137–147.

52. BrunnerD, DuckerK, OellersN, HafenE, ScholzH, et al. (1994) The ETS domain protein pointed-P2 is a target of MAP kinase in the sevenless signal transduction pathway. Nature 370: 386–389.

53. HalfonMS, CarmenaA, GisselbrechtS, SackersonCM, JimenezF, et al. (2000) Ras pathway specificity is determined by the integration of multiple signal-activated and tissue-restricted transcription factors. Cell 103: 63–74.

54. ReraM, BahadoraniS, ChoJ, KoehlerCL, UlgheraitM, et al. (2011) Modulation of longevity and tissue homeostasis by the Drosophila PGC-1 homolog. Cell Metab 14: 623–634.

55. BuchonN, OsmanD, DavidFP, FangHY, BoqueteJP, et al. (2013) Morphological and molecular characterization of adult midgut compartmentalization in Drosophila. Cell Rep 3: 1725–1738.

56. MarianesA, SpradlingAC (2013) Physiological and stem cell compartmentalization within the Drosophila midgut. Elife 2: e00886.

57. NegreN, BrownCD, MaL, BristowCA, MillerSW, et al. (2011) A cis-regulatory map of the Drosophila genome. Nature 471: 527–531.

58. WebberJL, ZhangJ, CoteL, VivekanandP, NiX, et al. (2013) The relationship between long-range chromatin occupancy and polymerization of the Drosophila ETS family transcriptional repressor Yan. Genetics 193: 633–649.

59. ReraM, ClarkRI, WalkerDW (2012) Intestinal barrier dysfunction links metabolic and inflammatory markers of aging to death in Drosophila. Proc Natl Acad Sci U S A 109: 21528–21533.

60. ZhangW, ThompsonBJ, HietakangasV, CohenSM (2011) MAPK/ERK signaling regulates insulin sensitivity to control glucose metabolism in Drosophila. PLoS Genet 7: e1002429.

61. BrunetA, BonniA, ZigmondMJ, LinMZ, JuoP, et al. (1999) Akt promotes cell survival by phosphorylating and inhibiting a Forkhead transcription factor. Cell 96: 857–868.

62. RothemundS, LiouYC, DaviesPL, KrauseE, SonnichsenFD (1999) A new class of hexahelical insect proteins revealed as putative carriers of small hydrophobic ligands. Structure 7: 1325–1332.

63. GrahamLA, DaviesPL (2002) The odorant-binding proteins of Drosophila melanogaster: annotation and characterization of a divergent gene family. Gene 292: 43–55.

64. GronkeS, ClarkeD-F, BroughtonS, AndrewsTD, PartridgeL (2010) Molecular evolution and functional characterisation of Drosophila insulin-like peptides. PLoS Genet 6: e1000857.

65. BroughtonSJ, PiperMD, IkeyaT, BassTM, JacobsonJ, et al. (2005) Longer lifespan, altered metabolism, and stress resistance in Drosophila from ablation of cells making insulin-like ligands. Proc Natl Acad Sci U S A 102: 3105–3110.

66. LemmonMA, SchlessingerJ (2010) Cell signaling by receptor tyrosine kinases. Cell 141: 1117–1134.

67. RoggeR, GreenPJ, UranoJ, Horn-SabanS, MlodzikM, et al. (1995) The role of yan in mediating the choice between cell division and differentiation. Development 121: 3947–3958.

68. FontanaL, PartridgeL, LongoVD (2010) Extending healthy life span–from yeast to humans. Science 328: 321–326.

69. GudbjartssonDF, WaltersGB, ThorleifssonG, StefanssonH, HalldorssonBV, et al. (2008) Many sequence variants affecting diversity of adult human height. Nat Genet 40: 609–615.

70. Lango AllenH, EstradaK, LettreG, BerndtSI, WeedonMN, et al. (2010) Hundreds of variants clustered in genomic loci and biological pathways affect human height. Nature 467: 832–838.

71. FujiiS, AmreinH (2002) Genes expressed in the Drosophila head reveal a role for fat cells in sex-specific physiology. EMBO J 21: 5353–5363.

72. RoignantJY, CarreC, MugatB, SzymczakD, LepesantJA, et al. (2003) Absence of transitive and systemic pathways allows cell-specific and isoform-specific RNAi in Drosophila. RNA 9: 299–308.

73. BassTM, GrandisonRC, WongR, MartinezP, PartridgeL, et al. (2007) Optimization of dietary restriction protocols in Drosophila. J Gerontol A Biol Sci Med Sci 62: 1071–1081.

74. AlicN, HoddinottMP, VintiG, PartridgeL (2011) Lifespan extension by increased expression of the Drosophila homologue of the IGFBP7 tumour suppressor. Aging Cell 10: 137–147.

75. BroughtonS, AlicN, SlackC, BassT, IkeyaT, et al. (2008) Reduction of DILP2 in Drosophila triages a metabolic phenotype from lifespan revealing redundancy and compensation among DILPs. PLoS One 3: e3721.

76. ChoksiSP, SouthallTD, BossingT, EdoffK, de WitE, et al. (2006) Prospero acts as a binary switch between self-renewal and differentiation in Drosophila neural stem cells. Dev Cell 11: 775–789.

77. SmythGK, SpeedT (2003) Normalization of cDNA microarray data. Methods 31: 265–273.

78. GentlemanRC, CareyVJ, BatesDM, BolstadB, DettlingM, et al. (2004) Bioconductor: open software development for computational biology and bioinformatics. Genome Biol 5: R80.

79. ToedlingJ, SkylarO, KruegerT, FischerJJ, SperlingS, et al. (2007) Ringo–an R/Bioconductor package for analyzing ChIP-chip readouts. BMC Bioinformatics 8: 221.

80. ZacherB, KuanPF, TreschA (2010) Starr: Simple Tiling ARRay analysis of Affymetrix ChIP-chip data. BMC Bioinformatics 11: 194.

81. BickelP, BoleyN, BrownJ, HuangH, ZhangN (2010) Subsampling Methods for Genomic Inference. Ann Appl Stat 4: 1660–1697.

82. BolstadBM, IrizarryRA, AstrandM, SpeedTP (2003) A comparison of normalization methods for high density oligonucleotide array data based on variance and bias. Bioinformatics 19: 185–193.

83. IrizarryRA, BolstadBM, CollinF, CopeLM, HobbsB, et al. (2003) Summaries of Affymetrix GeneChip probe level data. Nucleic Acids Res 31: e15.

84. IrizarryRA, HobbsB, CollinF, Beazer-BarclayYD, AntonellisKJ, et al. (2003) Exploration, normalization, and summaries of high density oligonucleotide array probe level data. Biostatistics 4: 249–264.

85. BenjaminiY, HochbergY (1995) Controlling the False Discovery Rate: A practical and Powerful Approach to Multiple Testing. J R Stat Soc Ser B Stat Methodol 57: 289–300.

86. Huang daW, ShermanBT, LempickiRA (2009) Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc 4: 44–57.

87. MusselC, HopfensitzM, KestlerHA (2010) BoolNet–an R package for generation, reconstruction and analysis of Boolean networks. Bioinformatics 26: 1378–1380.