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Rejuvenating Bi(d)ology

Oncogene volume 32, pages 3213–3219 (2013)Cite this article

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Abstract

The BH3-only Bid protein is a critical sentinel of cellular stress in the liver and the hematopoietic system. Bid’s initial ‘claim to fame’ came from its ability—as a caspase-truncated product—to trigger the mitochondrial apoptotic program following death receptor activation. Today we know that Bid can response to multiple types of proteases, which are activated under different conditions such as T-cell activation, ischemical reperfusion injury and lysosomal injury. Activation of the mitochondrial apoptotic program by Bid—via its recently identified receptor mitochondrial carrier homolog 2—involves multiple mechanisms, including release of cytochrome c and second mitochondria-derived activator of caspase (Smac), alteration of mitochondrial cristae organization, generation of reactive oxygen species and engagement of the permeability transition pore. Bid is also emerging—in its full-length form—as a pivotal sentinel of DNA damage in the bone marrow regulated by the ataxia telangiectasia mutated (ATM)/ataxia telangiectasia and Rad3-related (ATR) kinases. The ATM/ATR-Bid pathway is critically involved in preserving the quiescence and survival of hematopoietic stem cells both in the absence and presence of external stress, and a large part of this review will be dedicated to recent advances in this area of research.

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References

  1. Danial NN, Korsmeyer SJ . Cell death: critical control points. Cell 2004; 116: 205–219.

    Article  CAS  PubMed  Google Scholar 

  2. Wang K, Yin XM, Chao DT, Milliman CL, Korsmeyer SJ . BID: a novel BH3 domain-only death agonist. Genes Dev 1996; 10: 2859–2869.

    Article  CAS  PubMed  Google Scholar 

  3. Li H, Zhu H, Xu CJ, Yuan J . Cleavage of BID by caspase 8 mediates the mitochondrial damage in the Fas pathway of apoptosis. Cell 1998; 94: 491–501.

    Article  CAS  PubMed  Google Scholar 

  4. Luo X, Budihardjo I, Zou H, Slaughter C, Wang X . Bid a Bcl2 interacting protein, mediates cytochrome c release from mitochondria in response to activation of cell surface death receptors. Cell 1998; 94: 481–490.

    Article  CAS  PubMed  Google Scholar 

  5. Gross A, Yin XM, Wang K, Wei MC, Jockel J, Milliman C et al. Caspase cleaved BID targets mitochondria and is required for cytochrome c release, while BCL-XL prevents this release but not tumor necrosis factor-R1/Fas death. J Biol Chem 1999; 274: 1156–1163.

    Article  CAS  PubMed  Google Scholar 

  6. Yin XM . Bid, a BH3-only multi-functional molecule, is at the cross road of life and death. Gene 2006; 369: 7–19.

    Article  CAS  PubMed  Google Scholar 

  7. Sarig R, Zaltsman Y, Marcellus RC, Flavell R, Mak TW, Gross A . BID-D59A is a potent inducer of apoptosis in primary embryonic fibroblasts. J Biol Chem 2003; 278: 10707–10715.

    Article  CAS  PubMed  Google Scholar 

  8. Scaffidi C, Fulda S, Srinivasan A, Friesen C, Li F, Tomaselli KJ et al. Two CD95 (APO-1/Fas) signaling pathways. Embo J 1998; 17: 1675–1687.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  9. Yin XM, Wang K, Gross A, Zhao Y, Zinkel S, Klocke B et al. Bid-deficient mice are resistant to Fas-induced hepatocellular apoptosis. Nature 1999; 400: 886–891.

    Article  CAS  PubMed  Google Scholar 

  10. McKenzie MD, Carrington EM, Kaufmann T, Strasser A, Huang DC, Kay TW et al. Proapoptotic BH3-only protein Bid is essential for death receptor-induced apoptosis of pancreatic beta-cells. Diabetes 2008; 57: 1284–1292.

    Article  CAS  PubMed  Google Scholar 

  11. Li S, Zhao Y, He X, Kim T-H, Kuharsky DK, Rabinowich H et al. Relief of extrinsic pathway inhibition by the Bid-dependent mitochondrial release of Smac in Fas-mediated hepatocyte apoptosis. J Biol Chem 2002; 277: 26912–26920.

    Article  CAS  PubMed  Google Scholar 

  12. Eckelman BP, Salvesen GS, Scott FL . Human inhibitor of apoptosis proteins: why XIAP is the black sheep of the family. EMBO Rep 2006; 7: 988–994.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  13. Shi Y . A conserved tetrapeptide motif: potentiating apoptosis through IAP-binding. Cell Death Differ 2002; 9: 93–95.

    Article  CAS  PubMed  Google Scholar 

  14. Sun XM, Bratton SB, Butterworth M, MacFarlane M, Cohen GM . Bcl-2 and Bcl-xL inhibit CD95-mediated apoptosis by preventing mitochondrial release of Smac/DIABLO and subsequent inactivation of X-linked inhibitor-of-apoptosis protein. J Biol Chem 2002; 277: 11345–11351.

    Article  CAS  PubMed  Google Scholar 

  15. Jost PJ, Grabow S, Gray D, McKenzie MD, Nachbur U, Huang DC et al. XIAP discriminates between type I and type II FAS-induced apoptosis. Nature 2009; 460: 1035–1039.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  16. Zhao Y, Difrancesca D, Wang X, Zarnegar R, Michalopoulos GK, Yin XM . Promotion of Fas-mediated apoptosis in type II cells by high doses of hepatocyte growth factor bypasses the mitochondrial requirement. J Cell Physiol 2007; 213: 556–563.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  17. Wang X, DeFrances MC, Dai Y, Pediaditakis P, Johnson C, Bell A et al. A mechanism of cell survival: sequestration of Fas by the HGF receptor Met. Mol Cell 2002; 9: 411–421.

    Article  CAS  PubMed  Google Scholar 

  18. Walter D, Schmich K, Vogel S, Pick R, Kaufmann T, Hochmuth FC et al. Switch from type II to I Fas/CD95 death signaling on in vitro culturing of primary hepatocytes. Hepatology 2008; 48: 1942–1953.

    Article  CAS  PubMed  Google Scholar 

  19. Schungel S, Buitrago-Molina LE, Nalapareddy P, Lebofsky M, Manns MP, Jaeschke H et al. The strength of the Fas ligand signal determines whether hepatocytes act as type 1 or type 2 cells in murine livers. Hepatology 2009; 50: 1558–1566.

    Article  PubMed  Google Scholar 

  20. Ding WX, Ni HM, DiFrancesca D, Stolz DB, Yin XM . Bid-dependent generation of oxygen radicals promotes death receptor activation-induced apoptosis in murine hepatocytes. Hepatology 2004; 40: 403–413.

    Article  CAS  PubMed  Google Scholar 

  21. Zhao Y, Ding WX, Qian T, Watkins S, Lemasters JJ, Yin XM . Bid activates multiple mitochondrial apoptotic mechanisms in primary hepatocytes after death receptor engagement. Gastroenterology 2003; 125: 854–867.

    Article  CAS  PubMed  Google Scholar 

  22. Zhao Y, Li S, Childs EE, Kuharsky DK, Yin X-M . Activation of pro-death Bcl-2 family proteins and mitochondria apoptosis pathway in tumor necrosis factor-alpha -induced liver injury. J Biol Chem 2001; 276: 27432–27440.

    Article  CAS  PubMed  Google Scholar 

  23. Deng Y, Lin Y, Wu X . TRAIL-induced apoptosis requires Bax-dependent mitochondrial release of Smac/DIABLO. Genes Dev 2002; 16: 33–45.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  24. Broaddus VC, Dansen TB, Abayasiriwardana KS, Wilson SM, Finch AJ, Swigart LB et al. Bid mediates apoptotic synergy between tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and DNA damage. J Biol Chem 2005; 280: 12486–12493.

    Article  CAS  PubMed  Google Scholar 

  25. Chen X, Ding WX, Ni HM, Gao W, Shi YH, Gambotto AA et al. Bid-independent mitochondrial activation in tumor necrosis factor alpha-induced apoptosis and liver injury. Mol Cell Biol 2007; 27: 541–553.

    Article  CAS  PubMed  Google Scholar 

  26. Kaufmann T, Tai L, Ekert PG, Huang DC, Norris F, Lindemann RK et al. The BH3-only protein bid is dispensable for DNA damage- and replicative stress-induced apoptosis or cell-cycle arrest. Cell 2007; 129: 423–433.

    Article  CAS  PubMed  Google Scholar 

  27. Kaufmann T, Jost PJ, Pellegrini M, Puthalakath H, Gugasyan R, Gerondakis S et al. Fatal hepatitis mediated by tumor necrosis factor TNFalpha requires caspase-8 and involves the BH3-only proteins Bid and Bim. Immunity 2009; 30: 56–66.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  28. Ni HM, Chen X, Ding WX, Schuchmann M, Yin XM . Differential roles of JNK in ConA/GalN and ConA-induced liver injury in mice. Am J Pathol 2008; 173: 962–972.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  29. Ni HM, Chen X, Shi YH, Liao Y, Beg AA, Fan J et al. Genetic delineation of the pathways mediated by bid and JNK in tumor necrosis factor-alpha-induced liver injury in adult and embryonic mice. J Biol Chem 2009; 284: 4373–4382.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  30. Schmich K, Schlatter R, Corazza N, Sa Ferreira K, Ederer M, Brunner T et al. Tumor necrosis factor alpha sensitizes primary murine hepatocytes to Fas/CD95-induced apoptosis in a Bim- and Bid-dependent manner. Hepatology 2011; 53: 282–292.

    Article  CAS  PubMed  Google Scholar 

  31. Hikita H, Takehara T, Kodama T, Shimizu S, Hosui A, Miyagi T et al. BH3-only protein bid participates in the Bcl-2 network in healthy liver cells. Hepatology 2009; 50: 1972–1980.

    Article  CAS  PubMed  Google Scholar 

  32. Hikita H, Takehara T, Shimizu S, Kodama T, Li W, Miyagi T et al. Mcl-1 and Bcl-xL cooperatively maintain integrity of hepatocytes in developing and adult murine liver. Hepatology 2009; 50: 1217–1226.

    Article  CAS  PubMed  Google Scholar 

  33. Kim TH, Zhao Y, Ding WX, Shin JN, He X, Seo YW et al. Bid-cardiolipin interaction at mitochondrial contact site contributes to mitochondrial cristae reorganization and cytochrome C release. Mol Biol Cell 2004; 15: 3061–3072.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  34. Scorrano L, Ashiya M, Buttle K, Weiler S, Oakes SA, Mannella CA et al. A distinct pathway remodels mitochondrial cristae and mobilizes cytochrome c during apoptosis. Dev Cell 2002; 2: 55–67.

    Article  CAS  PubMed  Google Scholar 

  35. Kuwana T, Mackey MR, Perkins G, Ellisman MH, Latterich M, Schneiter R et al. Bid, Bax, and lipids cooperate to form supramolecular openings in the outer mitochondrial membrane. Cell 2002; 111: 331–342.

    Article  CAS  PubMed  Google Scholar 

  36. Ott M, Zhivotovsky B, Orrenius S . Role of cardiolipin in cytochrome c release from mitochondria. Cell Death Differ 2007; 14: 1243–1247.

    Article  CAS  PubMed  Google Scholar 

  37. Yamaguchi R, Lartigue L, Perkins G, Scott RT, Dixit A, Kushnareva Y et al. Opa1-mediated cristae opening is Bax/Bak and BH3 dependent, required for apoptosis, and independent of Bak oligomerization. Mol Cell 2008; 31: 557–569.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  38. Cheng EH, Wei MC, Weiler S, Flavell RA, Mak TW, Lindsten T et al. BCL-2, BCL-X(L) sequester BH3 domain-only molecules preventing BAX- and BAK-mediated mitochondrial apoptosis. Mol Cell 2001; 8: 705–711.

    Article  CAS  PubMed  Google Scholar 

  39. Desagher S, Osen-Sand A, Nichols A, Eskes R, Montessuit S, Lauper S et al. Bid-induced conformational change of Bax is responsible for mitochondrial cytochrome c release during apoptosis. J Cell Biol 1999; 144: 891–901.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  40. Wei MC, Lindsten T, Mootha VK, Weiler S, Gross A, Ashiya M et al. tBID, a membrane-targeted death ligand, oligomerizes BAK to release cytochrome c. Genes Dev 2000; 14: 2060–2071.

    CAS  PubMed  PubMed Central  Google Scholar 

  41. Grinberg M, Schwarz M, Zaltsman Y, Eini T, Niv H, Pietrokovski S et al. Mitochondrial carrier homolog 2 is a target of tBID in cells signaled to die by tumor necrosis factor alpha. Mol Cell Biol 2005; 25: 4579–4590.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  42. Zaltsman Y, Shachnai L, Yivgi-Ohana N, Schwarz M, Maryanovich M, Houtkooper RH et al. MTCH2/MIMP is a major facilitator of tBID recruitment to mitochondria. Nat Cell Biol 2010; 12: 553–562.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  43. Lutter M, Fang M, Luo X, Nishijima M, Xie X, Wang X . Cardiolipin provides specificity for targeting of tBid to mitochondria. Nat Cell Biol 2000; 2: 754–761.

    Article  CAS  PubMed  Google Scholar 

  44. Liu J, Weiss A, Durrant D, Chi NW, Lee RM . The cardiolipin-binding domain of Bid affects mitochondrial respiration and enhances cytochrome c release. Apoptosis 2004; 9: 533–541.

    Article  CAS  PubMed  Google Scholar 

  45. Bai L, Ni HM, Chen X, DiFrancesca D, Yin XM . Deletion of Bid impedes cell proliferation and hepatic carcinogenesis. Am J Pathol 2005; 166: 1523–1532.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  46. Ni HM, Baty CJ, Li N, Ding WX, Gao W, Li M et al. Bid agonist regulates murine hepatocyte proliferation by controlling endoplasmic reticulum calcium homeostasis. Hepatology 2010; 52: 338–348.

    Article  CAS  PubMed  Google Scholar 

  47. Cory S, Huang DC, Adams JM . The Bcl-2 family: roles in cell survival and oncogenesis. Oncogene 2003; 22: 8590–8607.

    Article  CAS  PubMed  Google Scholar 

  48. Jones RG, Bui T, White C, Madesh M, Krawczyk CM, Lindsten T et al. The proapoptotic factors Bax and Bak regulate T cell proliferation through control of endoplasmic reticulum Ca(2+) homeostasis. Immunity 2007; 27: 268–280.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  49. Scorrano L, Oakes SA, Opferman JT, Cheng EH, Sorcinelli MD, Pozzan T et al. BAX and BAK regulation of endoplasmic reticulum Ca2+: a control point for apoptosis. Science 2003; 300: 135–139.

    Article  CAS  PubMed  Google Scholar 

  50. Oakes SA, Scorrano L, Opferman JT, Bassik MC, Nishino M, Pozzan T et al. Proapoptotic BAX and BAK regulate the type 1 inositol trisphosphate receptor and calcium leak from the endoplasmic reticulum. Proc Natl Acad Sci USA 2005; 102: 105–110.

    Article  CAS  PubMed  Google Scholar 

  51. White C, Li C, Yang J, Petrenko NB, Madesh M, Thompson CB et al. The endoplasmic reticulum gateway to apoptosis by Bcl-X(L) modulation of the InsP3R. Nat Cell Biol 2005; 7: 1021–1028.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  52. Vail ME, Chaisson ML, Thompson J, Fausto N . Bcl-2 expression delays hepatocyte cell cycle progression during liver regeneration. Oncogene 2002; 21: 1548–1555.

    Article  CAS  PubMed  Google Scholar 

  53. Orford KW, Scadden DT . Deconstructing stem cell self-renewal: genetic insights into cell-cycle regulation. Nat Rev Genet 2008; 9: 115–128.

    Article  CAS  PubMed  Google Scholar 

  54. Akashi K, He X, Chen J, Iwasaki H, Niu C, Steenhard B et al. Transcriptional accessibility for genes of multiple tissues and hematopoietic lineages is hierarchically controlled during early hematopoiesis. Blood 2003; 101: 383–389.

    Article  CAS  PubMed  Google Scholar 

  55. Cheng T, Rodrigues N, Shen H, Yang Y, Dombkowski D, Sykes M et al. Hematopoietic stem cell quiescence maintained by p21cip1/waf1. Science 2000; 287: 1804–1808.

    Article  CAS  PubMed  Google Scholar 

  56. Hock H, Hamblen MJ, Rooke HM, Schindler JW, Saleque S, Fujiwara Y et al. Gfi-1 restricts proliferation and preserves functional integrity of haematopoietic stem cells. Nature 2004; 431: 1002–1007.

    Article  CAS  PubMed  Google Scholar 

  57. Liu Y, Bertram CC, Shi Q, Zinkel SS . Proapoptotic Bid mediates the Atr-directed DNA damage response to replicative stress. Cell Death Differ 2011; 18: 841–852.

    Article  CAS  PubMed  Google Scholar 

  58. Zinkel SS, Ong CC, Ferguson DO, Iwasaki H, Akashi K, Bronson RT et al. Proapoptotic BID is required for myeloid homeostasis and tumor suppression. Genes Dev 2003; 17: 229–239.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  59. Kamer I, Sarig R, Zaltsman Y, Niv H, Oberkovitz G, Regev L et al. Proapoptotic BID is an ATM effector in the DNA-damage response. Cell 2005; 122: 593–603.

    Article  CAS  PubMed  Google Scholar 

  60. Zinkel SS, Hurov KE, Ong C, Abtahi FM, Gross A, Korsmeyer SJ . A role for proapoptotic BID in the DNA-damage response. Cell 2005; 122: 579–591.

    Article  CAS  PubMed  Google Scholar 

  61. Mohrin M, Bourke E, Alexander D, Warr MR, Barry-Holson K, Le Beau MM et al. Hematopoietic stem cell quiescence promotes error-prone DNA repair and mutagenesis. Cell Stem Cell 2010; 7: 174–185.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  62. Liu Y, Aiello A, Zinkel SS . Bid protects the mouse hematopoietic system following hydroxyurea-induced replicative stress. Cell Death Differ 2012; 19: 1602–1612.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  63. Shen H, Yu H, Liang PH, Xufeng R, Song Y, Hu X et al. Bid is a positive regulator for donor-derived lymphoid cell regeneration in gamma-irradiated recipients. Exp Hematol 2011; 39: 947–57 e1.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  64. Mandal M, Crusio KM, Meng F, Liu S, Kinsella M, Clark MR et al. Regulation of lymphocyte progenitor survival by the proapoptotic activities of Bim and Bid. Proc Natl Acad Sci USA 2008; 105: 20840–20845.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Maryanovich M, Oberkovitz G, Niv H, Vorobiyov L, Zaltsman Y, Brenner O et al. The ATM-BID pathway regulates the quiescence and survival of haematopoietic stem cells. Nat Cell Biol 2012; 14: 535–541.

    Article  CAS  PubMed  Google Scholar 

  66. Liu Y, Vaithiyalingam S, Shi Q, Chazin WJ, Zinkel SS . BID binds to replication protein A and stimulates ATR function following replicative stress. Mol Cell Biol 2011; 31: 4298–4309.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  67. Ito K, Hirao A, Arai F, Matsuoka S, Takubo K, Hamaguchi I et al. Regulation of oxidative stress by ATM is required for self-renewal of haematopoietic stem cells. Nature 2004; 431: 997–1002.

    Article  CAS  PubMed  Google Scholar 

  68. Jang YY, Sharkis SJ . A low level of reactive oxygen species selects for primitive hematopoietic stem cells that may reside in the low-oxygenic niche. Blood 2007; 110: 3056–3063.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  69. Parmar K, Mauch P, Vergilio JA, Sackstein R, Down JD . Distribution of hematopoietic stem cells in the bone marrow according to regional hypoxia. Proc Natl Acad Sci USA 2007; 104: 5431–5436.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Tesio M, Golan K, Corso S, Giordano S, Schajnovitz A, Vagima Y et al. Enhanced c-Met activity promotes G-CSF-induced mobilization of hematopoietic progenitor cells via ROS signaling. Blood 2011; 117: 419–428.

    Article  CAS  PubMed  Google Scholar 

  71. Juntilla MM, Patil VD, Calamito M, Joshi RP, Birnbaum MJ, Koretzky GA . AKT1 and AKT2 maintain hematopoietic stem cell function by regulating reactive oxygen species. Blood 2010; 115: 4030–4038.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  72. Ito K, Hirao A, Arai F, Takubo K, Matsuoka S, Miyamoto K et al. Reactive oxygen species act through p38 MAPK to limit the lifespan of hematopoietic stem cells. Nat Med 2006; 12: 446–451.

    Article  CAS  PubMed  Google Scholar 

  73. Barlow C, Hirotsune S, Paylor R, Liyanage M, Eckhaus M, Collins F et al. Atm-deficient mice: a paradigm of ataxia telangiectasia. Cell 1996; 86: 159–171.

    Article  CAS  PubMed  Google Scholar 

  74. Celeste A, Petersen S, Romanienko PJ, Fernandez-Capetillo O, Chen HT, Sedelnikova OA et al. Genomic instability in mice lacking histone H2AX. Science 2002; 296: 922–927.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  75. Ward IM, Minn K, van Deursen J, Chen J . p53 Binding protein 53BP1 is required for DNA damage responses and tumor suppression in mice. Mol Cell Biol 2003; 23: 2556–2563.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  76. Sugiyama T, Kohara H, Noda M, Nagasawa T . Maintenance of the hematopoietic stem cell pool by CXCL12-CXCR4 chemokine signaling in bone marrow stromal cell niches. Immunity 2006; 25: 977–988.

    Article  CAS  PubMed  Google Scholar 

  77. Ito K, Takubo K, Arai F, Satoh H, Matsuoka S, Ohmura M et al. Regulation of reactive oxygen species by Atm is essential for proper response to DNA double-strand breaks in lymphocytes. J Immunol 2007; 178: 103–110.

    Article  CAS  PubMed  Google Scholar 

  78. Valentin-Vega YA, Maclean KH, Tait-Mulder J, Milasta S, Steeves M, Dorsey FC et al. Mitochondrial dysfunction in ataxia telangiectasia. Blood 2012; 119: 1490–1500.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  79. Edlich F, Banerjee S, Suzuki M, Cleland MM, Arnoult D, Wang C et al. Bcl-x(L) retrotranslocates Bax from the mitochondria into the cytosol. Cell 2011; 145: 104–116.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  80. Willer CJ, Speliotes EK, Loos RJ, Li S, Lindgren CM, Heid IM et al. Six new loci associated with body mass index highlight a neuronal influence on body weight regulation. Nat Genet 2009; 41: 25–34.

    Article  CAS  PubMed  Google Scholar 

  81. Schneider JG, Finck BN, Ren J, Standley KN, Takagi M, Maclean KH et al. ATM-dependent suppression of stress signaling reduces vascular disease in metabolic syndrome. Cell Metab 2006; 4: 377–389.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

AG is supported by the Israel Science Foundation, USA-Israel Binational Science Foundation and the German-Israel Foundation, and is the incumbent of the Armour Family Career Development Chair of Cancer Research.

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  1. S S Zinkel, X M Yin and A Gross: These authors contributed equally to this work.

Authors and Affiliations

  1. Departments of Medicine, Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, TN, USA

    S S Zinkel

  2. Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA

    X M Yin

  3. Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel

    A Gross

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Zinkel, S., Yin, X. & Gross, A. Rejuvenating Bi(d)ology. Oncogene 32, 3213–3219 (2013). https://doi.org/10.1038/onc.2012.454

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