1932
0
  1. Home
  2. A-Z Publications
  3. Annual Review of Genetics
  4. Volume 54, 2020
  5. Article

Annual Review of Genetics

Volume 54, 2020

Moonlighting Proteins

Abstract

The single gene, single protein, single function hypothesis is increasingly becoming obsolete. Numerous studies have demonstrated that individual proteins can moonlight, meaning they can have multiple functions based on their cellular or developmental context. In this review, we discuss moonlighting proteins, highlighting the biological pathways where this phenomenon may be particularly relevant. In addition, we combine genetic, cell biological, and evolutionary perspectives so that we can better understand how, when, and why moonlighting proteins may take on multiple roles.

Keyword(s): apoptosis, cancer, cell cycle, evolution, moonlighting, pathogenesis
Loading

Article metrics loading...

/content/journals/10.1146/annurev-genet-030620-102906
2020-11-23
2024-04-25
Loading full text...

Full text loading...

/deliver/fulltext/genet/54/1/annurev-genet-030620-102906.html?itemId=/content/journals/10.1146/annurev-genet-030620-102906&mimeType=html&fmt=ahah

Literature Cited

  1. 1. 
    Agarwal V, Hammerschmidt S, Malm S, Bergmann S, Riesbeck K, Blom AM 2012. Enolase of Streptococcus pneumoniae binds human complement inhibitor C4b-binding protein and contributes to complement evasion. J. Immunol. 189:3575–84
     [Google Scholar]
  2. 2. 
    Allen M, Cox C, Belbin O, Ma L, Bisceglio GD et al. 2012. Association and heterogeneity at the GAPDH locus in Alzheimer's disease. Neurobiol. Aging 33:1203.e25–33
     [Google Scholar]
  3. 3. 
    Alvarez RA, Blaylock MW, Baseman JB 2003. Surface localized glyceraldehyde-3-phosphate dehydrogenase of Mycoplasma genitalium binds mucin. Mol. Microbiol. 48:1417–25
     [Google Scholar]
  4. 4. 
    Ameisen JC. 2002. On the origin, evolution, and nature of programmed cell death: a timeline of four billion years. Cell Death Differ 9:367–93
     [Google Scholar]
  5. 5. 
    Aravind L, Koonin EV. 1998. The HORMA domain: a common structural denominator in mitotic checkpoints, chromosome synapsis and DNA repair. Trends Biochem. Sci. 23:284–86
     [Google Scholar]
  6. 6. 
    Baba T, Kobayashi H, Kawasaki H, Mineki R, Naito H, Ohmori D 2010. Glyceraldehyde-3-phosphate dehydrogenase interacts with phosphorylated Akt resulting from increased blood glucose in rat cardiac muscle. FEBS Lett 584:2796–800
     [Google Scholar]
  7. 7. 
    Bassik MC, Kampmann M, Lebbink RJ, Wang S, Hein MY et al. 2013. A systematic mammalian genetic interaction map reveals pathways underlying ricin susceptibility. Cell 152:909–22
     [Google Scholar]
  8. 8. 
    Behrends C, Sowa ME, Gygi SP, Harper JW 2010. Network organization of the human autophagy system. Nature 466:68–76
     [Google Scholar]
  9. 9. 
    Bergmann S, Rohde M, Chhatwal GS, Hammerschmidt S 2001. α-Enolase of Streptococcus pneumoniae is a plasmin(ogen)-binding protein displayed on the bacterial cell surface. Mol. Microbiol. 40:1273–87
     [Google Scholar]
  10. 10. 
    Bergmann S, Rohde M, Hammerschmidt S 2004. Glyceraldehyde-3-phosphate dehydrogenase of Streptococcus pneumoniae is a surface-displayed plasminogen-binding protein. Infect. Immun. 72:2416–19
     [Google Scholar]
  11. 11. 
    Bhat SP, Nagineni CN. 1989. αB subunit of lens-specific protein α-crystallin is present in other ocular and non-ocular tissues. Biochem. Biophys. Res. Commun. 158:319–25
     [Google Scholar]
  12. 12. 
    Bird A. 2020. The selfishness of law-abiding genes. Trends Genet 36:8–13
     [Google Scholar]
  13. 13. 
    Bloemendal H. 1977. The vertebrate eye lens. Science 197:127–38
     [Google Scholar]
  14. 14. 
    Boehning D, Patterson RL, Sedaghat L, Glebova NO, Kurosaki T, Snyder SH 2003. Cytochrome c binds to inositol (1,4,5) trisphosphate receptors, amplifying calcium-dependent apoptosis. Nat. Cell Biol. 5:1051–61
     [Google Scholar]
  15. 15. 
    Boleij A, Laarakkers CM, Gloerich J, Swinkels DW, Tjalsma H 2011. Surface-affinity profiling to identify host-pathogen interactions. Infect. Immun. 79:4777–83
     [Google Scholar]
  16. 16. 
    Bonafé N, Gilmore-Hebert M, Folk NL, Azodi M, Zhou Y, Chambers SK 2005. Glyceraldehyde-3-phosphate dehydrogenase binds to the AU-rich 3′ untranslated region of colony-stimulating factor-1 (CSF-1) messenger RNA in human ovarian cancer cells: possible role in CSF-1 posttranscriptional regulation and tumor phenotype. Cancer Res 65:3762–71
     [Google Scholar]
  17. 17. 
    Booth DG, Hood FE, Prior IA, Royle SJ 2011. A TACC3/ch-TOG/clathrin complex stabilises kinetochore fibres by inter-microtubule bridging. EMBO J 30:906–19
     [Google Scholar]
  18. 18. 
    Bornholdt ZA, Noda T, Abelson DM, Halfmann P, Wood MR et al. 2013. Structural rearrangement of Ebola virus VP40 begets multiple functions in the virus life cycle. Cell 154:763–74
     [Google Scholar]
  19. 19. 
    Brassard J, Gottschalk M, Quessy S 2004. Cloning and purification of the Streptococcussuis serotype 2 glyceraldehyde-3-phosphate dehydrogenase and its involvement as an adhesin. Vet. Microbiol. 102:87–94
     [Google Scholar]
  20. 20. 
    Brodehl A, Gaertner-Rommel A, Klauke B, Grewe SA, Schirmer I et al. 2017. The novel αB-crystallin (CRYAB) mutation p.D109G causes restrictive cardiomyopathy. Hum. Mutat. 38:947–52
     [Google Scholar]
  21. 21. 
    Brunet S, Sacher M. 2014. In sickness and in health: the role of TRAPP and associated proteins in disease. Traffic 15:803–18
     [Google Scholar]
  22. 22. 
    Butterfield DA, Hardas SS, Lange MLB 2010. Oxidatively modified glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and Alzheimer's disease: many pathways to neurodegeneration. J. Alzheimers Dis. 20:369–93
     [Google Scholar]
  23. 23. 
    Buttner EA, Gil-Krzewska AJ, Rajpurohit AK, Hunter CP 2007. Progression from mitotic catastrophe to germ cell death in Caenorhabditis elegans lis-1 mutants requires the spindle checkpoint. Dev. Biol. 305:397–410
     [Google Scholar]
  24. 24. 
    Buttner S, Eisenberg T, Carmona-Gutierrez D, Ruli D, Knauer H et al. 2007. Endonuclease G regulates budding yeast life and death. Mol. Cell 25:233–46
     [Google Scholar]
  25. 25. 
    Chapple CE, Robisson B, Spinelli L, Guien C, Becker E, Brun C 2015. Extreme multifunctional proteins identified from a human protein interaction network. Nat. Commun. 6:7412
     [Google Scholar]
  26. 26. 
    Chiche J, Pommier S, Beneteau M, Mondragón L, Meynet O et al. 2015. GAPDH enhances the aggressiveness and the vascularization of non-Hodgkin's B lymphomas via NF-κB-dependent induction of HIF-1α. Leukemia 29:1163–76
     [Google Scholar]
  27. 27. 
    Chirico N, Vianelli A, Belshaw R 2010. Why genes overlap in viruses. Proc. Biol. Sci. 277:3809–17
     [Google Scholar]
  28. 28. 
    Choi E, Kikuchi S, Gao H, Brodzik K, Nassour I et al. 2019. Mitotic regulators and the SHP2-MAPK pathway promote IR endocytosis and feedback regulation of insulin signaling. Nat. Commun. 10:1473
     [Google Scholar]
  29. 29. 
    Choi E, Zhang X, Xing C, Yu H 2016. Mitotic checkpoint regulators control insulin signaling and metabolic homeostasis. Cell 166:567–81
     [Google Scholar]
  30. 30. 
    Cianciotto NP. 2001. Pathogenicity of Legionella pneumophila. Int. J. Med. . Microbiol 291:331–43
     [Google Scholar]
  31. 31. 
    Clapier CR, Cairns BR. 2009. The biology of chromatin remodeling complexes. Annu. Rev. Biochem. 78:273–304
     [Google Scholar]
  32. 32. 
    Clark AR, Lubsen NH, Slingsby C 2012. sHSP in the eye lens: crystallin mutations, cataract and proteostasis. Int. J. Biochem. Cell Biol. 44:1687–97
     [Google Scholar]
  33. 33. 
    Coller HA. 2014. Is cancer a metabolic disease. ? Am. J. Pathol. 184:14–17
     [Google Scholar]
  34. 34. 
    Conant GC, Wolfe KH. 2008. Turning a hobby into a job: how duplicated genes find new functions. Nat. Rev. Genet. 9:938–50
     [Google Scholar]
  35. 35. 
    Copley SD. 2014. An evolutionary perspective on protein moonlighting. Biochem. Soc. Trans. 42:1684–91
     [Google Scholar]
  36. 36. 
    Danial NN, Gimenez-Cassina A, Tondera D 2010. Homeostatic functions of BCL-2 proteins beyond apoptosis. Adv. Exp. Med. Biol. 687:1–32
     [Google Scholar]
  37. 37. 
    Dietrich FS, Voegeli S, Brachat S, Lerch A, Gates K et al. 2004. The Ashbya gossypii genome as a tool for mapping the ancient Saccharomyces cerevisiae genome. Science 304:304–7
     [Google Scholar]
  38. 38. 
    Dubin RA, Wawrousek EF, Piatigorsky J 1989. Expression of the murine αB-crystallin gene is not restricted to the lens. Mol. Cell. Biol. 9:1083–91
     [Google Scholar]
  39. 39. 
    Dujon B, Sherman D, Fischer G, Durrens P, Casaregola S et al. 2004. Genome evolution in yeasts. Nature 430:35–44
     [Google Scholar]
  40. 40. 
    Esgleas M, Li YY, Hancock MA, Harel J, Dubreuil JD, Gottschalk M 2008. Isolation and characterization of α-enolase, a novel fibronectin-binding protein from Streptococcussuis. . Microbiology 154:2668–79
     [Google Scholar]
  41. 41. 
    Espinosa-Cantú A, Ascencio D, Barona-Gómez F, DeLuna A 2015. Gene duplication and the evolution of moonlighting proteins. Front. Genet. 6:227
     [Google Scholar]
  42. 42. 
    Espinosa-Cantú A, Ascencio D, Herrera-Basurto S, Xu J, Roguev A et al. 2018. Protein moonlighting revealed by noncatalytic phenotypes of yeast enzymes. Genetics 208:419–31
     [Google Scholar]
  43. 43. 
    Fallini C, Bassell GJ, Rossoll W 2012. Spinal muscular atrophy: the role of SMN in axonal mRNA regulation. Brain Res 1462:81–92
     [Google Scholar]
  44. 44. 
    Fares MA. 2014. The evolution of protein moonlighting: adaptive traps and promiscuity in the chaperonins. Biochem. Soc. Trans. 42:1709–14
     [Google Scholar]
  45. 45. 
    Feng YJ, Pan XZ, Sun W, Wang CJ, Zhang HM et al. 2009. Streptococcussuis enolase functions as a protective antigen displayed on the bacterial cell surface. J. Infect. Dis. 200:1583–92
     [Google Scholar]
  46. 46. 
    Franco-Serrano L, Cedano J, Perez-Pons JA, Mozo-Villarias A, Piñol J et al. 2018. A hypothesis explaining why so many pathogen virulence proteins are moonlighting proteins. Pathog. Dis. 76:fty046
     [Google Scholar]
  47. 47. 
    Franco-Serrano L, Huerta M, Hernandez S, Cedano J, Perez-Pons J et al. 2018. Multifunctional proteins: involvement in human diseases and targets of current drugs. Protein J 37:444–53
     [Google Scholar]
  48. 48. 
    Friedland JS, Shattock R, Remick DG, Griffin GE 1993. Mycobacterial 65-kD heat shock protein induces release of proinflammatory cytokines from human monocytic cells. Clin. Exp. Immunol. 91:58–62
     [Google Scholar]
  49. 49. 
    Fulde M, Rohde M, Polok A, Preissner KT, Chhatwal GS, Bergmann S 2013. Cooperative plasminogen recruitment to the surface of Streptococcus canis via M protein and enolase enhances bacterial survival. mBio 4:2e00629–12
     [Google Scholar]
  50. 50. 
    Ganapathy-Kanniappan S. 2018. Evolution of GAPDH as a druggable target of tumor glycolysis. ? Expert Opin. Ther. Tar. 22:295–98
     [Google Scholar]
  51. 51. 
    Gao X, Wang H, Yang JJ, Liu X, Liu ZR 2012. Pyruvate kinase M2 regulates gene transcription by acting as a protein kinase. Mol. Cell 45:598–609
     [Google Scholar]
  52. 52. 
    Ge JP, Catt DM, Gregory RL 2004. Streptococcus mutans surface α-enolase binds salivary mucin MG2 and human plasminogen. Infect. Immun. 72:6748–52
     [Google Scholar]
  53. 53. 
    Gomis-Rüth FX, Dessen A, Timmins J, Bracher A, Kolesnikowa L et al. 2003. The matrix protein VP40 from Ebola virus octamerizes into pore-like structures with specific RNA binding properties. Structure 11:423–33
     [Google Scholar]
  54. 54. 
    Green DR, Fitzgerald P. 2016. Just so stories about the evolution of apoptosis. Curr. Biol. 26:R620–27
     [Google Scholar]
  55. 55. 
    Hannibal L, Collins D, Brassard J, Chakravarti R, Vempati R et al. 2012. Heme binding properties of glyceraldehyde-3-phosphate dehydrogenase. Biochemistry 51:8514–29
     [Google Scholar]
  56. 56. 
    Hao Z, Duncan GS, Chang CC, Elia A, Fang M et al. 2005. Specific ablation of the apoptotic functions of cytochrome c reveals a differential requirement for cytochrome c and Apaf-1 in apoptosis. Cell 121:579–91
     [Google Scholar]
  57. 57. 
    Hara MR, Agrawal N, Kim SF, Cascio MB, Fujimuro M et al. 2005. S-nitrosylated GAPDH initiates apoptotic cell death by nuclear translocation following Siah1 binding. Nat. Cell Biol. 7:665–74
     [Google Scholar]
  58. 58. 
    Henderson B. 2014. An overview of protein moonlighting in bacterial infection. Biochem. Soc. Trans. 42:1720–27
     [Google Scholar]
  59. 59. 
    Henderson B, Martin A. 2011. Bacterial virulence in the moonlight: Multitasking bacterial moonlighting proteins are virulence determinants in infectious disease. Infect. Immun. 79:3476–91
     [Google Scholar]
  60. 60. 
    Hickey TB, Thorson LM, Speert DP, Daffe M, Stokes RW 2009. Mycobacterium tuberculosis Cpn60.2 and DnaK are located on the bacterial surface, where Cpn60.2 facilitates efficient bacterial association with macrophages. Infect. Immun. 77:3389–401
     [Google Scholar]
  61. 61. 
    Horwitz J. 1992. Alpha-crystallin can function as a molecular chaperone. PNAS 89:10449–53
     [Google Scholar]
  62. 62. 
    Huang QJ, Lan FH, Zheng ZY, Xie FL, Han JY et al. 2011. Akt2 kinase suppresses glyceraldehyde-3-phosphate dehydrogenase (GAPDH)-mediated apoptosis in ovarian cancer cells via phosphorylating GAPDH at threonine 237 and decreasing its nuclear translocation. J. Biol. Chem. 286:42211–20
     [Google Scholar]
  63. 63. 
    Ingolia TD, Craig EA. 1982. Four small Drosophila heat shock proteins are related to each other and to mammalian α-crystallin. PNAS 79:2360–64
     [Google Scholar]
  64. 64. 
    Itakura M, Nakajima H, Kubo T, Semi Y, Kume S et al. 2015. Glyceraldehyde-3-phosphate dehydrogenase aggregates accelerate amyloid-β amyloidogenesis in Alzheimer disease. J. Biol. Chem. 290:4326072–87
     [Google Scholar]
  65. 65. 
    Iwaki T, Kume-Iwaki A, Liem RK, Goldman JE 1989. αB-crystallin is expressed in non-lenticular tissues and accumulates in Alexander's disease brain. Cell 57:71–78
     [Google Scholar]
  66. 66. 
    Jacquin MA, Chiche J, Zunino B, Beneteau M, Meynet O et al. 2013. GAPDH binds to active Akt, leading to Bcl-xL increase and escape from caspase-independent cell death. Cell Death Differ 20:1043–54
     [Google Scholar]
  67. 67. 
    Jeffery CJ. 1999. Moonlighting proteins. Trends Biochem. Sci. 24:8–11
     [Google Scholar]
  68. 68. 
    Jeffery CJ. 2014. An introduction to protein moonlighting. Biochem. Soc. Trans. 42:1679–83
     [Google Scholar]
  69. 69. 
    Jiang X, Wang X. 2004. Cytochrome c-mediated apoptosis. Annu. Rev. Biochem. 73:87–106
     [Google Scholar]
  70. 70. 
    Jiang Y, Li X, Yang W, Hawke DH, Zheng Y et al. 2014. PKM2 regulates chromosome segregation and mitosis progression of tumor cells. Mol. Cell 53:75–87
     [Google Scholar]
  71. 71. 
    Jiang Y, Wang Y, Wang T, Hawke DH, Zheng Y et al. 2014. PKM2 phosphorylates MLC2 and regulates cytokinesis of tumour cells. Nat. Commun. 5:5566
     [Google Scholar]
  72. 72. 
    Kellis M, Birren BW, Lander ES 2004. Proof and evolutionary analysis of ancient genome duplication in the yeast Saccharomyces cerevisiae. . Nature 428:617–24
     [Google Scholar]
  73. 73. 
    Kesimer M, Kilic N, Mehrotra R, Thornton DJ, Sheehan JK 2009. Identification of salivary mucin MUC7 binding proteins from Streptococcus gordonii. . BMC Microbiol 9:163
     [Google Scholar]
  74. 74. 
    Khan IK, Bhuiyan M, Kihara D 2017. DextMP: deep dive into text for predicting moonlighting proteins. Bioinformatics 33:i83–91
     [Google Scholar]
  75. 75. 
    Kim JW, Kim SJ, Han SM, Paik SY, Hur SY et al. 1998. Increased glyceraldehyde-3-phosphate dehydrogenase gene expression in human cervical cancers. Gynecol. Oncol. 71:266–69
     [Google Scholar]
  76. 76. 
    Kim S, Lee J, Kim J 2007. Regulation of oncogenic transcription factor hTAFII68-TEC activity by human glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Biochem. J. 404:197–206
     [Google Scholar]
  77. 77. 
    Kops GJ. 2008. The kinetochore and spindle checkpoint in mammals. Front. Biosci. 13:3606–20
     [Google Scholar]
  78. 78. 
    Kops GJ, Weaver BA, Cleveland DW 2005. On the road to cancer: aneuploidy and the mitotic checkpoint. Nat. Rev. Cancer 5:773–85
     [Google Scholar]
  79. 79. 
    Kroemer G. 1997. Mitochondrial implication in apoptosis. Towards an endosymbiont hypothesis of apoptosis evolution. Cell Death Differ 4:443–56
     [Google Scholar]
  80. 80. 
    Lamb CA, Nuhlen S, Judith D, Frith D, Snijders AP et al. 2016. TBC1D14 regulates autophagy via the TRAPP complex and ATG9 traffic. EMBO J 35:281–301
     [Google Scholar]
  81. 81. 
    Lara-Gonzalez P, Westhorpe FG, Taylor SS 2012. The spindle assembly checkpoint. Curr. Biol. 22:R966–80
     [Google Scholar]
  82. 82. 
    Li LY, Luo X, Wang X 2001. Endonuclease G is an apoptotic DNase when released from mitochondria. Nature 412:95–99
     [Google Scholar]
  83. 83. 
    Li XJ, Jiang YH, Meisenhelder J, Yang WW, Hawke DH et al. 2016. Mitochondria-translocated PGK1 functions as a protein kinase to coordinate glycolysis and the TCA cycle in tumorigenesis. Mol. Cell 61:705–19
     [Google Scholar]
  84. 84. 
    Li Y, Nowotny P, Holmans P, Smemo S, Kauwe JSK et al. 2004. Association of late-onset Alzheimer's disease with genetic variation in multiple members of the GAPD gene family. PNAS 101:15688–93
     [Google Scholar]
  85. 85. 
    Liang J, Cao RX, Wang XJ, Zhang YJ, Wang P et al. 2017. Mitochondrial PKM2 regulates oxidative stress-induced apoptosis by stabilizing Bcl2. Cell Res 27:329–51
     [Google Scholar]
  86. 86. 
    Lin S-N, Ayada K, Zhao Y, Yokota K, Takenaka R et al. 2005. Helicobacter pylori heat-shock protein 60 induces production of the pro-inflammatory cytokine IL8 in monocytic cells. J. Med. Microbiol. 54:225–33
     [Google Scholar]
  87. 87. 
    Liu KY, Tang ZJ, Huang AM, Chen P, Liu PP et al. 2017. Glyceraldehyde-3-phosphate dehydrogenase promotes cancer growth and metastasis through upregulation of SNAIL expression. Int. J. Oncol. 50:252–62
     [Google Scholar]
  88. 88. 
    Liu X, Kim CN, Yang J, Jemmerson R, Wang X 1996. Induction of apoptotic program in cell-free extracts: requirement for dATP and cytochrome c. Cell 86:147–57
     [Google Scholar]
  89. 89. 
    Lu Y, Rolland SG, Conradt B 2011. A molecular switch that governs mitochondrial fusion and fission mediated by the BCL2-like protein CED-9 of Caenorhabditis elegans. . PNAS 108:E813–22
     [Google Scholar]
  90. 90. 
    Lu ZM, Hunter T. 2018. Metabolic kinases moonlighting as protein kinases. Trends Biochem. Sci. 43:301–10
     [Google Scholar]
  91. 91. 
    Luo X, Tang Z, Rizo J, Yu H 2002. The Mad2 spindle checkpoint protein undergoes similar major conformational changes upon binding to either Mad1 or Cdc20. Mol. Cell 9:59–71
     [Google Scholar]
  92. 92. 
    Luo X, Tang Z, Xia G, Wassmann K, Matsumoto T et al. 2004. The Mad2 spindle checkpoint protein has two distinct natively folded states. Nat. Struct. Mol. Biol. 11:338–45
     [Google Scholar]
  93. 93. 
    Madureira P, Baptista M, Vieira M, Magalhães V, Camelo A et al. 2007. Streptococcus agalactiae GAPDH is a virulence-associated immunomodulatory protein. J. Immunol. 178:1379–87
     [Google Scholar]
  94. 94. 
    Marioni RE, Harris SE, Zhang Q, McRae AF, Hagenaars SP et al. 2018. GWAS on family history of Alzheimer's disease. Transl. Psychiatry 8:199
     [Google Scholar]
  95. 95. 
    Martin ACR. 2014. Structural biology of moonlighting: lessons from antibodies. Biochem. Soc. Trans. 42:1704–8
     [Google Scholar]
  96. 96. 
    Milev MP, Hasaj B, Saint-Dic D, Snounou S, Zhao Q, Sacher M 2015. TRAMM/TrappC12 plays a role in chromosome congression, kinetochore stability, and CENP-E recruitment. J. Cell Biol. 209:221–34
     [Google Scholar]
  97. 97. 
    Milo R. 2013. What is the total number of protein molecules per cell volume? A call to rethink some published values. Bioessays 35:1050–55
     [Google Scholar]
  98. 98. 
    Mori Y, Yamaguchi M, Terao Y, Hamada S, Ooshima T, Kawabata S 2012. α-Enolase of Streptococcus pneumoniae induces formation of neutrophil extracellular traps. J. Biol. Chem. 287:10472–81
     [Google Scholar]
  99. 99. 
    Moscona AA, Fox L, Smith J, Degenstein L 1985. Antiserum to lens antigens immunostains Müller glia cells in the neural retina. PNAS 82:5570–73
     [Google Scholar]
  100. 100. 
    Muchmore SW, Sattler M, Liang H, Meadows RP, Harlan JE et al. 1996. X-ray and NMR structure of human Bcl-xL, an inhibitor of programmed cell death. Nature 381:335–41
     [Google Scholar]
  101. 101. 
    Pancholi V, Fischetti VA. 1992. A major surface protein on group A streptococci is a glyceraldehyde-3-phosphate-dehydrogenase with multiple binding activity. J. Exp. Med. 176:415–26
     [Google Scholar]
  102. 102. 
    Pancholi V, Fischetti VA. 1993. Glyceraldehyde-3-phosphate dehydrogenase on the surface of group A streptococci is also an ADP-ribosylating enzyme. PNAS 90:8154–58
     [Google Scholar]
  103. 103. 
    Pancholi V, Fischetti VA. 1997. Regulation of the phosphorylation of human pharyngeal cell proteins by group A streptococcal surface dehydrogenase: signal transduction between streptococci and pharyngeal cells. J. Exp. Med. 186:1633–43
     [Google Scholar]
  104. 104. 
    Piatigorsky J, O'Brien WE, Norman BL, Kalumuck K, Wistow GJ et al. 1988. Gene sharing by delta-crystallin and argininosuccinate lyase. PNAS 85:3479–83
     [Google Scholar]
  105. 105. 
    Piatigorsky J, Wistow GJ. 1989. Enzyme/crystallins: gene sharing as an evolutionary strategy. Cell 57:197–99
     [Google Scholar]
  106. 106. 
    Popgeorgiev N, Bonneau B, Ferri KF, Prudent J, Thibaut J, Gillet G 2011. The apoptotic regulator Nrz controls cytoskeletal dynamics via the regulation of Ca2+ trafficking in the zebrafish blastula. Dev. Cell 20:663–76
     [Google Scholar]
  107. 107. 
    Qian X, Li XJ, Lu ZM 2017. Protein kinase activity of the glycolytic enzyme PGK1 regulates autophagy to promote tumorigenesis. Autophagy 13:1246–47
     [Google Scholar]
  108. 108. 
    Quessy S, Busque P, Higgins R, Jacques M, Dubreuil JD 1997. Description of an albumin binding activity for Streptococcussuis serotype 2. FEMS Microbiol. Lett. 147:245–50
     [Google Scholar]
  109. 109. 
    Ramos D, Pellin-Carcelen A, Agusti J, Murgui A, Jorda E et al. 2015. Deregulation of glyceraldehyde-3-phosphate dehydrogenase expression during tumor progression of human cutaneous melanoma. Anticancer Res 35:439–44
     [Google Scholar]
  110. 110. 
    Revillion F, Pawlowski V, Hornez L, Peyrat JP 2000. Glyceraldehyde-3-phosphate dehydrogenase gene expression in human breast cancer. Eur. J. Cancer 36:1038–42
     [Google Scholar]
  111. 111. 
    Rice AM, McLysaght A. 2017. Dosage-sensitive genes in evolution and disease. BMC Biol 15:78
     [Google Scholar]
  112. 112. 
    Rolland SG, Lu Y, David CN, Conradt B 2009. The BCL-2-like protein CED-9 of C. elegans promotes FZO-1/Mfn1,2- and EAT-3/Opa1-dependent mitochondrial fusion. J. Cell Biol. 186:525–40
     [Google Scholar]
  113. 113. 
    Rosenberg SC, Corbett KD. 2015. The multifaceted roles of the HORMA domain in cellular signaling. J. Cell Biol. 211:745–55
     [Google Scholar]
  114. 114. 
    Royle SJ. 2011. Mitotic moonlighting functions for membrane trafficking proteins. Traffic 12:791–98
     [Google Scholar]
  115. 115. 
    Royle SJ, Bright NA, Lagnado L 2005. Clathrin is required for the function of the mitotic spindle. Nature 434:1152–57
     [Google Scholar]
  116. 116. 
    Royle SJ, Lagnado L. 2006. Trimerisation is important for the function of clathrin at the mitotic spindle. J. Cell Sci. 119:4071–78
     [Google Scholar]
  117. 117. 
    Schek N, Hall BL, Finn OJ 1988. Increased glyceraldehyde-3-phosphate dehydrogenase gene expression in human pancreatic adenocarcinoma. Cancer Res 48:6354–59
     [Google Scholar]
  118. 118. 
    Scrivens PJ, Noueihed B, Shahrzad N, Hul S, Brunet S, Sacher M 2011. C4orf41 and TTC-15 are mammalian TRAPP components with a role at an early stage in ER-to-Golgi trafficking. Mol. Biol. Cell 22:2083–93
     [Google Scholar]
  119. 119. 
    Sen N, Hara MR, Kornberg MD, Cascio MB, Bae BI et al. 2008. Nitric oxide-induced nuclear GAPDH activates p300/CBP and mediates apoptosis. Nat. Cell Biol. 10:866–73
     [Google Scholar]
  120. 120. 
    Sigler PB, Xu Z, Rye HS, Burston SG, Fenton WA, Horwich AL 1998. Structure and function in GroEL-mediated protein folding. Annu. Rev. Biochem. 67:581–608
     [Google Scholar]
  121. 121. 
    Sironi L, Mapelli M, Knapp S, De Antoni A, Jeang KT, Musacchio A 2002. Crystal structure of the tetrameric Mad1–Mad2 core complex: implications of a ‘safety belt’ binding mechanism for the spindle checkpoint. EMBO J 21:2496–506
     [Google Scholar]
  122. 122. 
    Sirover MA. 2017. Glyceraldehyde-3-Phosphate Dehydrogenase (GAPDH): The Quintessential Moonlighting Protein in Normal Cell Function and in Human Disease London: Elsevier/Academic
  123. 123. 
    Sirover MA. 2018. Pleiotropic effects of moonlighting glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in cancer progression, invasiveness, and metastases. Cancer Metast. Rev. 37:665–76
     [Google Scholar]
  124. 124. 
    Sriram G, Martinez JA, McCabe ER, Liao JC, Dipple KM 2005. Single-gene disorders: What role could moonlighting enzymes play. ? Am. J. Hum. Genet. 76:911–24
     [Google Scholar]
  125. 125. 
    Strich R. 2015. Programmed cell death initiation and execution in budding yeast. Genetics 200:1003–14
     [Google Scholar]
  126. 126. 
    Stump AD, Dillon-White M, Gu S 2013. Molecular evolution of the moonlighting protein SMN in metazoans. Comp. Biochem. Phys. D 8:220–30
     [Google Scholar]
  127. 127. 
    Sunaga K, Takahashi H, Chuang D-M, Ishitani R 1995. Glyceraldehyde-3‐phosphate dehydrogenase is over‐expressed during apoptotic death of neuronal cultures and is recognized by a monoclonal antibody against amyloid plaques from Alzheimer's brain. Neurosci. Lett. 200:133–36
     [Google Scholar]
  128. 128. 
    Suzuki Y, Imai Y, Nakayama H, Takahashi K, Takio K, Takahashi R 2001. A serine protease, HtrA2, is released from the mitochondria and interacts with XIAP, inducing cell death. Mol. Cell 8:613–21
     [Google Scholar]
  129. 129. 
    Tait SW, Green DR. 2010. Mitochondria and cell death: outer membrane permeabilization and beyond. Nat. Rev. Mol. Cell Biol. 11:621–32
     [Google Scholar]
  130. 130. 
    Tamaoka A, Endoh R, Shoji S, Takahashi H, Hirokawa K et al. 1996. Antibodies to amyloid β protein (Aβ) crossreact with glyceraldehyde-3‐phosphate dehydrogenase (GAPDH). Neurobiol. Aging 17:405–14
     [Google Scholar]
  131. 131. 
    Tang ZJ, Yuan SQ, Hu YM, Zhang H, Wu WJ et al. 2012. Over-expression of GAPDH in human colorectal carcinoma as a preferred target of 3-bromopyruvate propyl ester. J. Bioenerg. Biomembr. 44:117–25
     [Google Scholar]
  132. 132. 
    Tarze A, Deniaud A, Le Bras M, Maillier E, Molle D et al. 2007. GAPDH, a novel regulator of the pro-apoptotic mitochondrial membrane permeabilization. Oncogene 26:2606–20
     [Google Scholar]
  133. 133. 
    Teichner A, Eytan E, Sitry-Shevah D, Miniowitz-Shemtov S, Dumin E et al. 2011. p31comet promotes disassembly of the mitotic checkpoint complex in an ATP-dependent process. PNAS 108:3187–92
     [Google Scholar]
  134. 134. 
    Terao Y, Yamaguchi M, Hamada S, Kawabata S 2006. Multifunctional glyceraldehyde-3-phosphate dehydrogenase of Streptococcus pyogenes is essential for evasion from neutrophils. J. Biol. Chem. 281:14215–23
     [Google Scholar]
  135. 135. 
    Tokunaga K, Nakamura Y, Sakata K, Fujimori K, Ohkubo M et al. 1987. Enhanced expression of a glyceraldehyde-3-phosphate dehydrogenase gene in human-lung cancers. Cancer Res 47:5616–19
     [Google Scholar]
  136. 136. 
    Vila MR, Nicolas A, Morote J, de Torres I, Meseguer A 2000. Increased glyceraldehyde-3-phosphate dehydrogenase expression in renal cell carcinoma identified by RNA-based, arbitrarily primed polymerase chain reaction. Cancer 89:152–64
     [Google Scholar]
  137. 137. 
    Wan J, Block S, Scribano CM, Thiry R, Esbona K et al. 2019. Mad1 destabilizes p53 by preventing PML from sequestering MDM2. Nat. Commun. 10:1540
     [Google Scholar]
  138. 138. 
    Wan J, Zhu F, Zasadil LM, Yu J, Wang L et al. 2014. A Golgi-localized pool of the mitotic checkpoint component Mad1 controls integrin secretion and cell migration. Curr. Biol. 24:2687–92
     [Google Scholar]
  139. 139. 
    Wang Q, Woltjer RL, Cimino PJ, Pan C, Montine KS et al. 2005. Proteomic analysis of neurofibrillary tangles in Alzheimer disease identifies GAPDH as a detergent-insoluble paired helical filament tau binding protein. FASEB J 19:869–71
     [Google Scholar]
  140. 140. 
    Wang WF, Jeffery CJ. 2016. An analysis of surface proteomics results reveals novel candidates for intracellular/surface moonlighting proteins in bacteria. Mol. Biosyst. 12:1420–31
     [Google Scholar]
  141. 141. 
    Westhorpe FG, Tighe A, Lara-Gonzalez P, Taylor SS 2011. p31comet-mediated extraction of Mad2 from the MCC promotes efficient mitotic exit. J. Cell Sci. 124:3905–16
     [Google Scholar]
  142. 142. 
    Wistow GJ, Mulders JW, de Jong WW 1987. The enzyme lactate dehydrogenase as a structural protein in avian and crocodilian lenses. Nature 326:622–24
     [Google Scholar]
  143. 143. 
    Wolfe KH, Shields DC. 1997. Molecular evidence for an ancient duplication of the entire yeast genome. Nature 387:708–13
     [Google Scholar]
  144. 144. 
    Xia L, Qin K, Wang X-R, Wang X-L, Zhou A-W et al. 2017. Pyruvate kinase M2 phosphorylates H2AX and promotes genomic instability in human tumor cells. Oncotarget 8:109120–34
     [Google Scholar]
  145. 145. 
    Yang M, Li B, Tomchick DR, Machius M, Rizo J et al. 2007. p31comet blocks Mad2 activation through structural mimicry. Cell 131:744–55
     [Google Scholar]
  146. 146. 
    Yang W, Xia Y, Hawke D, Li X, Liang J et al. 2012. PKM2 phosphorylates histone H3 and promotes gene transcription and tumorigenesis. Cell 150:685–96
     [Google Scholar]
  147. 147. 
    Yokoyama H, Nakos K, Santarella-Mellwig R, Rybina S, Krijgsveld J et al. 2013. CHD4 is a RanGTP-dependent MAP that stabilizes microtubules and regulates bipolar spindle formation. Curr. Biol. 23:2443–51
     [Google Scholar]
  148. 148. 
    Yokoyama H, Rybina S, Santarella-Mellwig R, Mattaj IW, Karsenti E 2009. ISWI is a RanGTP-dependent MAP required for chromosome segregation. J. Cell Biol. 187:813–29
     [Google Scholar]
  149. 149. 
    Yoshida N, Oeda K, Watanabe E, Mikami T, Fukita Y et al. 2001. Protein function. Chaperonin turned insect toxin. Nature 411:44
     [Google Scholar]
  150. 150. 
    Youle RJ, Strasser A. 2008. The BCL-2 protein family: opposing activities that mediate cell death. Nat. Rev. Mol. Cell Biol. 9:47–59
     [Google Scholar]
  151. 151. 
    Zmasek CM, Godzik A. 2013. Evolution of the animal apoptosis network. Cold Spring Harb. Perspect. Biol. 5:a008649
     [Google Scholar]
/content/journals/10.1146/annurev-genet-030620-102906
Loading
Moonlighting Proteins
Annual Review of Genetics 54, 265 (2020); https://doi.org/10.1146/annurev-genet-030620-102906
/content/journals/10.1146/annurev-genet-030620-102906
/content/journals/10.1146/annurev-genet-030620-102906
Loading

Data & Media loading...

  • Article Type: Review Article

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error