Molecular Neurobiology

, Volume 43, Issue 2, pp 114–123 | Cite as

The Role of PML in the Nervous System



The promyeloctic leukemia protein PML is a tumor suppressor that was originally identified due to its involvement in the (15;17) translocation of acute promyelocytic leukemia. While the majority of early research has focused upon the role of PML in the pathogenesis of leukemia, more recent evidence has identified important roles for PML in tissues outside the hemopoietic system, including the central nervous system (CNS). Here, we review recent literature on the role of PML in the CNS, with particular focus on the processes of neurodevelopment and neurodegeneration, and propose new lines of investigation.


PML PML nuclear body CNS Neural stem cell Neurodegeneration 



We apologize for any omission of references, which was due to space limitations. Laboratory is supported by the Samantha Dickson Brain Tumour Trust and the Wellcome Trust.


  1. 1.
    Grimwade D, Solomon E (1997) Characterisation of the PML/RAR alpha rearrangement associated with t(15;17) acute promyelocytic leukaemia. Curr Top Microbiol Immunol 220:81–112PubMedGoogle Scholar
  2. 2.
    Melnick A, Fruchtman S, Zelent A, Liu M, Huang Q, Boczkowska B et al (1999) Identification of novel chromosomal rearrangements in acute myelogenous leukemia involving loci on chromosome 2p23, 15q22 and 17q21. Leukemia 13:1534–1538PubMedGoogle Scholar
  3. 3.
    Melnick A, Licht JD (1999) Deconstructing a disease: RARalpha, its fusion partners, and their roles in the pathogenesis of acute promyelocytic leukemia. Blood 93:3167–3215PubMedGoogle Scholar
  4. 4.
    Salomoni P, Pandolfi PP (2002) The role of PML in tumor suppression. Cell 108:165–170PubMedGoogle Scholar
  5. 5.
    Reymond A, Meroni G, Fantozzi A, Merla G, Cairo S, Luzi L et al (2001) The tripartite motif family identifies cell compartments. EMBO J 20:2140–2151PubMedGoogle Scholar
  6. 6.
    Deshaies RJ, Joazeiro CA (2009) RING domain E3 ubiquitin ligases. Annu Rev Biochem 78:399–434PubMedGoogle Scholar
  7. 7.
    Meroni G, Diez-Roux G (2005) TRIM/RBCC, a novel class of ‘single protein RING finger’ E3 ubiquitin ligases. Bioessays 27:1147–1157PubMedGoogle Scholar
  8. 8.
    Burkhard P, Stetefeld J, Strelkov SV (2001) Coiled coils: a highly versatile protein folding motif. Trends Cell Biol 11:82–88PubMedGoogle Scholar
  9. 9.
    Borden KL, Boddy MN, Lally J, O'Reilly NJ, Martin S, Howe K et al (1995) The solution structure of the RING finger domain from the acute promyelocytic leukaemia proto-oncoprotein PML. EMBO J 14:1532–1541PubMedGoogle Scholar
  10. 10.
    Borden KL, Lally JM, Martin SR, O'Reilly NJ, Solomon E, Freemont PS (1996) In vivo and in vitro characterization of the B1 and B2 zinc-binding domains from the acute promyelocytic leukemia protooncoprotein PML. Proc Natl Acad Sci U S A 93:1601–1606PubMedGoogle Scholar
  11. 11.
    Fagioli M, Alcalay M, Tomassoni L, Ferrucci PF, Mencarelli A, Riganelli D et al (1998) Cooperation between the RING + B1-B2 and coiled-coil domains of PML is necessary for its effects on cell survival. Oncogene 16:2905–2913PubMedGoogle Scholar
  12. 12.
    Condemine W, Takahashi Y, Zhu J, Puvion-Dutilleul F, Guegan S, Janin A et al (2006) Characterization of endogenous human promyelocytic leukemia isoforms. Cancer Res 66:6192–6198PubMedGoogle Scholar
  13. 13.
    Fagioli M, Alcalay M, Pandolfi PP, Venturini L, Mencarelli A, Simeone A et al (1992) Alternative splicing of PML transcripts predicts coexpression of several carboxy-terminally different protein isoforms. Oncogene 7:1083–1091PubMedGoogle Scholar
  14. 14.
    Jensen K, Shiels C, Freemont PS (2001) PML protein isoforms and the RBCC/TRIM motif. Oncogene 20:7223–7233PubMedGoogle Scholar
  15. 15.
    Nisole S, Stoye JP, Saib A (2005) TRIM family proteins: retroviral restriction and antiviral defence. Nat Rev Microbiol 3:799–808PubMedGoogle Scholar
  16. 16.
    Lin HK, Bergmann S, Pandolfi PP (2004) Cytoplasmic PML function in TGF-beta signalling. Nature 431:205–211PubMedGoogle Scholar
  17. 17.
    Salomoni P, Bellodi C (2007) New insights into the cytoplasmic function of PML. Histol Histopathol 22:937–946PubMedGoogle Scholar
  18. 18.
    Condemine W, Takahashi Y, Le Bras M, de The H (2007) A nucleolar targeting signal in PML-I addresses PML to nucleolar caps in stressed or senescent cells. J Cell Sci 120:3219–3227PubMedGoogle Scholar
  19. 19.
    Bischof O, Kirsh O, Pearson M, Itahana K, Pelicci PG, Dejean A (2002) Deconstructing PML-induced premature senescence. EMBO J 21:3358–3369PubMedGoogle Scholar
  20. 20.
    Guo A, Salomoni P, Luo J, Shih A, Zhong S, Gu W et al (2000) The function of PML in p53-dependent apoptosis. Nat Cell Biol 2:730–736PubMedGoogle Scholar
  21. 21.
    Borden KL (2002) Pondering the promyelocytic leukemia protein (PML) puzzle: possible functions for PML nuclear bodies. Mol Cell Biol 22:5259–5269PubMedGoogle Scholar
  22. 22.
    Chang KS, Fan YH, Andreeff M, Liu J, Mu ZM (1995) The PML gene encodes a phosphoprotein associated with the nuclear matrix. Blood 85:3646–3653PubMedGoogle Scholar
  23. 23.
    Duprez E, Saurin AJ, Desterro JM, Lallemand-Breitenbach V, Howe K, Boddy MN et al (1999) SUMO-1 modification of the acute promyelocytic leukaemia protein PML: implications for nuclear localisation. J Cell Sci 112(Pt 3):381–393PubMedGoogle Scholar
  24. 24.
    Bernardi R, Scaglioni PP, Bergmann S, Horn HF, Vousden KH, Pandolfi PP (2004) PML regulates p53 stability by sequestering Mdm2 to the nucleolus. Nat Cell Biol 6:665–672PubMedGoogle Scholar
  25. 25.
    Yang S, Kuo C, Bisi JE, Kim MK (2002) PML-dependent apoptosis after DNA damage is regulated by the checkpoint kinase hCds1/Chk2. Nat Cell Biol 4:865–870PubMedGoogle Scholar
  26. 26.
    Ishov AM, Sotnikov AG, Negorev D, Vladimirova OV, Neff N, Kamitani T et al (1999) PML is critical for ND10 formation and recruits the PML-interacting protein daxx to this nuclear structure when modified by SUMO-1. J Cell Biol 147:221–234PubMedGoogle Scholar
  27. 27.
    Zhong S, Salomoni P, Pandolfi PP (2000) The transcriptional role of PML and the nuclear body. Nat Cell Biol 2:E85–E90PubMedGoogle Scholar
  28. 28.
    Stuurman N, de Graaf A, Floore A, Josso A, Humbel B, de Jong L et al (1992) A monoclonal antibody recognizing nuclear matrix-associated nuclear bodies. J Cell Sci 101(Pt 4):773–784PubMedGoogle Scholar
  29. 29.
    Dellaire G, Bazett-Jones DP (2004) PML nuclear bodies: dynamic sensors of DNA damage and cellular stress. Bioessays 26:963–977PubMedGoogle Scholar
  30. 30.
    Boisvert FM, Hendzel MJ, Bazett-Jones DP (2000) Promyelocytic leukemia (PML) nuclear bodies are protein structures that do not accumulate RNA. J Cell Biol 148:283–292PubMedGoogle Scholar
  31. 31.
    Eskiw CH, Dellaire G, Bazett-Jones DP (2004) Chromatin contributes to structural integrity of promyelocytic leukemia bodies through a SUMO-1-independent mechanism. J Biol Chem 279:9577–9585PubMedGoogle Scholar
  32. 32.
    Wang J, Shiels C, Sasieni P, Wu PJ, Islam SA, Freemont PS et al (2004) Promyelocytic leukemia nuclear bodies associate with transcriptionally active genomic regions. J Cell Biol 164:515–526PubMedGoogle Scholar
  33. 33.
    Kumar PP, Bischof O, Purbey PK, Notani D, Urlaub H, Dejean A et al (2007) Functional interaction between PML and SATB1 regulates chromatin-loop architecture and transcription of the MHC class I locus. Nat Cell Biol 9:45–56PubMedGoogle Scholar
  34. 34.
    Shiels C, Islam SA, Vatcheva R, Sasieni P, Sternberg MJ, Freemont PS et al (2001) PML bodies associate specifically with the MHC gene cluster in interphase nuclei. J Cell Sci 114:3705–3716PubMedGoogle Scholar
  35. 35.
    Ayaydin F, Dasso M (2004) Distinct in vivo dynamics of vertebrate SUMO paralogues. Mol Biol Cell 15:5208–5218PubMedGoogle Scholar
  36. 36.
    Fu C, Ahmed K, Ding H, Ding X, Lan J, Yang Z et al (2005) Stabilization of PML nuclear localization by conjugation and oligomerization of SUMO-3. Oncogene 24:5401–5413PubMedGoogle Scholar
  37. 37.
    Kamitani T, Nguyen HP, Kito K, Fukuda-Kamitani T, Yeh ET (1998) Covalent modification of PML by the sentrin family of ubiquitin-like proteins. J Biol Chem 273:3117–3120PubMedGoogle Scholar
  38. 38.
    Soignet SL, Maslak P, Wang ZG, Jhanwar S, Calleja E, Dardashti LJ et al (1998) Complete remission after treatment of acute promyelocytic leukemia with arsenic trioxide. N Engl J Med 339:1341–1348PubMedGoogle Scholar
  39. 39.
    Zhu J, Lallemand-Breitenbach V, de The H (2001) Pathways of retinoic acid- or arsenic trioxide-induced PML/RARalpha catabolism, role of oncogene degradation in disease remission. Oncogene 20:7257–7265PubMedGoogle Scholar
  40. 40.
    Jeanne M, Lallemand-Breitenbach V, Ferhi O, Koken M, Le Bras M, Duffort S et al (2010) PML/RARA oxidation and arsenic binding initiate the antileukemia response of As2O3. Cancer Cell 18:88–98PubMedGoogle Scholar
  41. 41.
    Lallemand-Breitenbach V, de The H (2010) PML nuclear bodies. Cold Spring Harb Perspect Biol 2:a000661PubMedGoogle Scholar
  42. 42.
    Aoto T, Saitoh N, Ichimura T, Niwa H, Nakao M (2006) Nuclear and chromatin reorganization in the MHC-Oct3/4 locus at developmental phases of embryonic stem cell differentiation. Dev Biol 298:354–367PubMedGoogle Scholar
  43. 43.
    Flenghi L, Fagioli M, Tomassoni L, Pileri S, Gambacorta M, Pacini R et al (1995) Characterization of a new monoclonal antibody (PG-M3) directed against the aminoterminal portion of the PML gene product: immunocytochemical evidence for high expression of PML proteins on activated macrophages, endothelial cells, and epithelia. Blood 85:1871–1880PubMedGoogle Scholar
  44. 44.
    Gambacorta M, Flenghi L, Fagioli M, Pileri S, Leoncini L, Bigerna B et al (1996) Heterogeneous nuclear expression of the promyelocytic leukemia (PML) protein in normal and neoplastic human tissues. Am J Pathol 149:2023–2035PubMedGoogle Scholar
  45. 45.
    Terris B, Baldin V, Dubois S, Degott C, Flejou JF, Henin D et al (1995) PML nuclear bodies are general targets for inflammation and cell proliferation. Cancer Res 55:1590–1597PubMedGoogle Scholar
  46. 46.
    Li W, Ferguson BJ, Khaled WT, Tevendale M, Stingl J, Poli V et al (2009) PML depletion disrupts normal mammary gland development and skews the composition of the mammary luminal cell progenitor pool. Proc Natl Acad Sci U S A 106(12):4725–4730PubMedGoogle Scholar
  47. 47.
    Everett RD, Chelbi-Alix MK (2007) PML and PML nuclear bodies: implications in antiviral defence. Biochimie 89:819–830PubMedGoogle Scholar
  48. 48.
    Stadler M, Chelbi-Alix MK, Koken MH, Venturini L, Lee C, Saib A et al (1995) Transcriptional induction of the PML growth suppressor gene by interferons is mediated through an ISRE and a GAS element. Oncogene 11:2565–2573PubMedGoogle Scholar
  49. 49.
    Ferbeyre G, de Stanchina E, Querido E, Baptiste N, Prives C, Lowe SW (2000) PML is induced by oncogenic ras and promotes premature senescence. Genes Dev 14:2015–2027PubMedGoogle Scholar
  50. 50.
    Pearson M, Carbone R, Sebastiani C, Cioce M, Fagioli M, Saito S et al (2000) PML regulates p53 acetylation and premature senescence induced by oncogenic Ras. Nature 406:207–210PubMedGoogle Scholar
  51. 51.
    de Stanchina E, Querido E, Narita M, Davuluri RV, Pandolfi PP, Ferbeyre G et al (2004) PML is a direct p53 target that modulates p53 effector functions. Mol Cell 13:523–535PubMedGoogle Scholar
  52. 52.
    Jiang WQ, Zhong ZH, Henson JD, Reddel RR (2007) Identification of candidate alternative lengthening of telomeres genes by methionine restriction and RNA interference. Oncogene 26:4635–4647PubMedGoogle Scholar
  53. 53.
    Stagno D’Alcontres M, Mendez-Bermudez A, Foxon JL, Royle NJ, Salomoni P (2007) Lack of TRF2 in ALT cells causes PML-dependent p53 activation and loss of telomeric DNA. J Cell Biol 179:855–867PubMedGoogle Scholar
  54. 54.
    Goldberg AD, Banaszynski LA, Noh KM, Lewis PW, Elsaesser SJ, Stadler S et al (2010) Distinct factors control histone variant H3.3 localization at specific genomic regions. Cell 140:678–691PubMedGoogle Scholar
  55. 55.
    Lewis PW, Elsaesser SJ, Noh KM, Stadler SC, Allis CD (2010) Daxx is an H3.3-specific histone chaperone and cooperates with ATRX in replication-independent chromatin assembly at telomeres. Proc Natl Acad Sci U S A 107:14075–14080PubMedGoogle Scholar
  56. 56.
    Seeler JS, Marchio A, Sitterlin D, Transy C, Dejean A (1998) Interaction of SP100 with HP1 proteins: a link between the promyelocytic leukemia-associated nuclear bodies and the chromatin compartment. Proc Natl Acad Sci U S A 95:7316–7321PubMedGoogle Scholar
  57. 57.
    He D, Mu ZM, Le X, Hsieh JT, Pong RC, Chung LW et al (1997) Adenovirus-mediated expression of PML suppresses growth and tumorigenicity of prostate cancer cells. Cancer Res 57:1868–1872PubMedGoogle Scholar
  58. 58.
    Le XF, Yang P, Chang KS (1996) Analysis of the growth and transformation suppressor domains of promyelocytic leukemia gene, PML. J Biol Chem 271:130–135PubMedGoogle Scholar
  59. 59.
    Mu ZM, Le XF, Vallian S, Glassman AB, Chang KS (1997) Stable overexpression of PML alters regulation of cell cycle progression in HeLa cells. Carcinogenesis 18:2063–2069PubMedGoogle Scholar
  60. 60.
    Le XF, Vallian S, Mu ZM, Hung MC, Chang KS (1998) Recombinant PML adenovirus suppresses growth and tumorigenicity of human breast cancer cells by inducing G1 cell cycle arrest and apoptosis. Oncogene 16:1839–1849PubMedGoogle Scholar
  61. 61.
    Alcalay M, Tomassoni L, Colombo E, Stoldt S, Grignani F, Fagioli M et al (1998) The promyelocytic leukemia gene product (PML) forms stable complexes with the retinoblastoma protein. Mol Cell Biol 18:1084–1093PubMedGoogle Scholar
  62. 62.
    Campisi J, d’Adda di Fagagna F (2007) Cellular senescence: when bad things happen to good cells. Nat Rev Mol Cell Biol 8:729–740PubMedGoogle Scholar
  63. 63.
    Serrano M, Lin AW, McCurrach ME, Beach D, Lowe SW (1997) Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a. Cell 88:593–602PubMedGoogle Scholar
  64. 64.
    Regad T, Bellodi C, Nicotera P, Salomoni P (2009) The tumor suppressor Pml regulates cell fate in the developing neocortex. Nat Neurosci 12:132–140PubMedGoogle Scholar
  65. 65.
    Bernardi R, Pandolfi PP (2003) Role of PML and the PML-nuclear body in the control of programmed cell death. Oncogene 22:9048–9057PubMedGoogle Scholar
  66. 66.
    Takahashi Y, Lallemand-Breitenbach V, Zhu J, de The H (2004) PML nuclear bodies and apoptosis. Oncogene 23:2819–2824PubMedGoogle Scholar
  67. 67.
    Trotman LC, Alimonti A, Scaglioni PP, Koutcher JA, Cordon-Cardo C, Pandolfi PP (2006) Identification of a tumour suppressor network opposing nuclear Akt function. Nature 441:523–527PubMedGoogle Scholar
  68. 68.
    Wang ZG, Ruggero D, Ronchetti S, Zhong S, Gaboli M, Rivi R et al (1998) PML is essential for multiple apoptotic pathways. Nat Genet 20:266–272PubMedGoogle Scholar
  69. 69.
    Quignon F, De Bels F, Koken M, Feunteun J, Ameisen JC, de The H (1998) PML induces a novel caspase-independent death process. Nat Genet 20:259–265PubMedGoogle Scholar
  70. 70.
    Fogal V, Gostissa M, Sandy P, Zacchi P, Sternsdorf T, Jensen K et al (2000) Regulation of p53 activity in nuclear bodies by a specific PML isoform. EMBO J 19:6185–6195PubMedGoogle Scholar
  71. 71.
    Salomoni P, Khelifi AF (2006) Daxx: death or survival protein? Trends Cell Biol 16:97–104PubMedGoogle Scholar
  72. 72.
    Khelifi AF, D’Alcontres MS, Salomoni P (2005) Daxx is required for stress-induced cell death and JNK activation. Cell Death Differ 12:724–733PubMedGoogle Scholar
  73. 73.
    Gurrieri C, Capodieci P, Bernardi R, Scaglioni PP, Nafa K, Rush LJ et al (2004) Loss of the tumor suppressor PML in human cancers of multiple histologic origins. J Natl Cancer Inst 96:269–279PubMedGoogle Scholar
  74. 74.
    Lee HE, Jee CD, Kim MA, Lee HS, Lee YM, Lee BL et al (2007) Loss of promyelocytic leukemia protein in human gastric cancers. Cancer Lett 247:103–109PubMedGoogle Scholar
  75. 75.
    Zhang P, Chin W, Chow LT, Chan AS, Yim AP, Leung SF et al (2000) Lack of expression for the suppressor PML in human small cell lung carcinoma. Int J Cancer 85:599–605PubMedGoogle Scholar
  76. 76.
    Koken MH, Linares-Cruz G, Quignon F, Viron A, Chelbi-Alix MK, Sobczak-Thepot J et al (1995) The PML growth-suppressor has an altered expression in human oncogenesis. Oncogene 10:1315–1324PubMedGoogle Scholar
  77. 77.
    Yoon GS, Yu E (2001) Overexpression of promyelocytic leukemia protein and alteration of PML nuclear bodies in early stage of hepatocarcinogenesis. J Korean Med Sci 16:433–438PubMedGoogle Scholar
  78. 78.
    Gray PA, Fu H, Luo P, Zhao Q, Yu J, Ferrari A et al (2004) Mouse brain organization revealed through direct genome-scale TF expression analysis. Science 306:2255–2257PubMedGoogle Scholar
  79. 79.
    Ito K, Bernardi R, Morotti A, Matsuoka S, Saglio G, Ikeda Y et al (2008) PML targeting eradicates quiescent leukaemia-initiating cells. Nature 453(7198):1072–1078PubMedGoogle Scholar
  80. 80.
    Woulfe J, Gray D, Prichett-Pejic W, Munoz DG, Chretien M (2004) Intranuclear rodlets in the substantia nigra: interactions with marinesco bodies, ubiquitin, and promyelocytic leukemia protein. J Neuropathol Exp Neurol 63:1200–1207PubMedGoogle Scholar
  81. 81.
    Woulfe JM, Prichett-Pejic W, Rippstein P, Munoz DG (2007) Promyelocytic leukaemia-immunoreactive neuronal intranuclear rodlets in the human brain. Neuropathol Appl Neurobiol 33:56–66PubMedGoogle Scholar
  82. 82.
    Villagra NT, Navascues J, Casafont I, Val-Bernal JF, Lafarga M, Berciano MT (2006) The PML-nuclear inclusion of human supraoptic neurons: a new compartment with SUMO-1- and ubiquitin-proteasome-associated domains. Neurobiol Dis 21:181–193PubMedGoogle Scholar
  83. 83.
    Villagra NT, Berciano J, Altable M, Navascues J, Casafont I, Lafarga M et al (2004) PML bodies in reactive sensory ganglion neurons of the Guillain-Barre syndrome. Neurobiol Dis 16:158–168PubMedGoogle Scholar
  84. 84.
    Berube NG, Mangelsdorf M, Jagla M, Vanderluit J, Garrick D, Gibbons RJ et al (2005) The chromatin-remodeling protein ATRX is critical for neuronal survival during corticogenesis. J Clin Invest 115:258–267PubMedGoogle Scholar
  85. 85.
    Ritchie K, Seah C, Moulin J, Isaac C, Dick F, Berube NG (2008) Loss of ATRX leads to chromosome cohesion and congression defects. J Cell Biol 180:315–324PubMedGoogle Scholar
  86. 86.
    Berube NG, Healy J, Medina CF, Wu S, Hodgson T, Jagla M et al (2007) Patient mutations alter ATRX targeting to PML nuclear bodies. Eur J Hum Genet 16(2):192–201PubMedGoogle Scholar
  87. 87.
    Salomoni P (2009) Stemming out of a new PML era? Cell Death Differ 16:1083–1092PubMedGoogle Scholar
  88. 88.
    Milyavsky M, Gan OI, Trottier M, Komosa M, Tabach O, Notta F et al (2010) A distinctive DNA damage response in human hematopoietic stem cells reveals an apoptosis-independent role for p53 in self-renewal. Cell Stem Cell 7:186–197PubMedGoogle Scholar
  89. 89.
    Schwamborn JC, Berezikov E, Knoblich JA (2009) The TRIM-NHL protein TRIM32 activates microRNAs and prevents self-renewal in mouse neural progenitors. Cell 136:913–925PubMedGoogle Scholar
  90. 90.
    Tuoc TC, Stoykova A (2008) Trim11 modulates the function of neurogenic transcription factor Pax6 through ubiquitin-proteosome system. Genes Dev 22:1972–1986PubMedGoogle Scholar
  91. 91.
    Chai Y, Koppenhafer SL, Shoesmith SJ, Perez MK, Paulson HL (1999) Evidence for proteasome involvement in polyglutamine disease: localization to nuclear inclusions in SCA3/MJD and suppression of polyglutamine aggregation in vitro. Hum Mol Genet 8:673–682PubMedGoogle Scholar
  92. 92.
    Kaytor MD, Duvick LA, Skinner PJ, Koob MD, Ranum LP, Orr HT (1999) Nuclear localization of the spinocerebellar ataxia type 7 protein, ataxin-7. Hum Mol Genet 8:1657–1664PubMedGoogle Scholar
  93. 93.
    Klement IA, Skinner PJ, Kaytor MD, Yi H, Hersch SM, Clark HB et al (1998) Ataxin-1 nuclear localization and aggregation: role in polyglutamine-induced disease in SCA1 transgenic mice. Cell 95:41–53PubMedGoogle Scholar
  94. 94.
    Takahashi J, Fujigasaki H, Iwabuchi K, Bruni AC, Uchihara T, El Hachimi KH et al (2003) PML nuclear bodies and neuronal intranuclear inclusion in polyglutamine diseases. Neurobiol Dis 13:230–237PubMedGoogle Scholar
  95. 95.
    Takahashi J, Fujigasaki H, Zander C, El Hachimi KH, Stevanin G, Durr A et al (2002) Two populations of neuronal intranuclear inclusions in SCA7 differ in size and promyelocytic leukaemia protein content. Brain 125:1534–1543PubMedGoogle Scholar
  96. 96.
    Yamada M, Sato T, Shimohata T, Hayashi S, Igarashi S, Tsuji S et al (2001) Interaction between neuronal intranuclear inclusions and promyelocytic leukemia protein nuclear and coiled bodies in CAG repeat diseases. Am J Pathol 159:1785–1795PubMedGoogle Scholar
  97. 97.
    Mackenzie IR, Baker M, West G, Woulfe J, Qadi N, Gass J et al (2006) A family with tau-negative frontotemporal dementia and neuronal intranuclear inclusions linked to chromosome 17. Brain 129:853–867PubMedGoogle Scholar
  98. 98.
    Kumada S, Uchihara T, Hayashi M, Nakamura A, Kikuchi E, Mizutani T et al (2002) Promyelocytic leukemia protein is redistributed during the formation of intranuclear inclusions independent of polyglutamine expansion: an immunohistochemical study on Marinesco bodies. J Neuropathol Exp Neurol 61:984–991PubMedGoogle Scholar
  99. 99.
    Imarisio S, Carmichael J, Korolchuk V, Chen CW, Saiki S, Rose C et al (2008) Huntington’s disease: from pathology and genetics to potential therapies. Biochem J 412:191–209PubMedGoogle Scholar
  100. 100.
    Scaglioni PP, Yung TM, Cai LF, Erdjument-Bromage H, Kaufman AJ, Singh B et al (2006) A CK2-dependent mechanism for degradation of the PML tumor suppressor. Cell 126:269–283PubMedGoogle Scholar
  101. 101.
    Lallemand-Breitenbach V, Zhu J, Puvion F, Koken M, Honore N, Doubeikovsky A et al (2001) Role of promyelocytic leukemia (PML) sumolation in nuclear body formation, 11S proteasome recruitment, and As2O3-induced PML or PML/retinoic acid receptor alpha degradation. J Exp Med 193:1361–1371PubMedGoogle Scholar
  102. 102.
    Zhang XW, Yan XJ, Zhou ZR, Yang FF, Wu ZY, Sun HB et al (2010) Arsenic trioxide controls the fate of the PML-RARalpha oncoprotein by directly binding PML. Science 328:240–243PubMedGoogle Scholar
  103. 103.
    Lafarga M, Berciano MT, Pena E, Mayo I, Castano JG, Bohmann D et al (2002) Clastosome: a subtype of nuclear body enriched in 19S and 20S proteasomes, ubiquitin, and protein substrates of proteasome. Mol Biol Cell 13:2771–2782PubMedGoogle Scholar
  104. 104.
    Janer A, Martin E, Muriel MP, Latouche M, Fujigasaki H, Ruberg M et al (2006) PML clastosomes prevent nuclear accumulation of mutant ataxin-7 and other polyglutamine proteins. J Cell Biol 174:65–76PubMedGoogle Scholar
  105. 105.
    Qin Q, Inatome R, Hotta A, Kojima M, Yamamura H, Hirai H et al (2006) A novel GTPase, CRAG, mediates promyelocytic leukemia protein-associated nuclear body formation and degradation of expanded polyglutamine protein. J Cell Biol 172:497–504PubMedGoogle Scholar
  106. 106.
    Nucifora FC Jr, Sasaki M, Peters MF, Huang H, Cooper JK, Yamada M et al (2001) Interference by huntingtin and atrophin-1 with cbp-mediated transcription leading to cellular toxicity. Science 291:2423–2428PubMedGoogle Scholar
  107. 107.
    Steffan JS, Kazantsev A, Spasic-Boskovic O, Greenwald M, Zhu YZ, Gohler H et al (2000) The Huntington’s disease protein interacts with p53 and CREB-binding protein and represses transcription. Proc Natl Acad Sci U S A 97:6763–6768PubMedGoogle Scholar
  108. 108.
    Hayashi T, Sasaki C, Iwai M, Sato K, Zhang WR, Warita H et al (2001) Induction of PML immunoreactivity in rat brain neurons after transient middle cerebral artery occlusion. Neurol Res 23:772–776PubMedGoogle Scholar
  109. 109.
    Wang ZG, Delva L, Gaboli M, Rivi R, Giorgio M, Cordon-Cardo C et al (1998) Role of PML in cell growth and the retinoic acid pathway. Science 279:1547–1551PubMedGoogle Scholar
  110. 110.
    Wichterle H, Przedborski S (2010) What can pluripotent stem cells teach us about neurodegenerative diseases? Nat Neurosci 13:800–804PubMedGoogle Scholar
  111. 111.
    Pardal R, Ortega-Saenz P, Duran R, Lopez-Barneo J (2007) Glia-like stem cells sustain physiologic neurogenesis in the adult mammalian carotid body. Cell 131:364–377PubMedGoogle Scholar
  112. 112.
    Zhu J, Zhou J, Peres L, Riaucoux F, Honore N, Kogan S et al (2005) A sumoylation site in PML/RARA is essential for leukemic transformation. Cancer Cell 7:143–153PubMedGoogle Scholar

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© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.Samantha Dickson Brain Cancer UnitUCL Cancer InstituteLondonUK

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