Sumoylation as a Signal for Polyubiquitylation and Proteasomal Degradation

  • Maria Miteva
  • Kirstin Keusekotten
  • Kay Hofmann
  • Gerrit J. K. Praefcke
  • R. Jürgen Dohmen
Part of the Subcellular Biochemistry book series (SCBI, volume 54)


The small ubiquitin-related modifier (SUMO) is a versatile cellular tool to modulate a protein’s function. SUMO modification is a reversible process analogous to ubiquitylation. The consecutive actions of E1, E2 and E3 enzymes catalyze the attachment of SUMO to target proteins, while deconjugation is promoted by SUMO specific proteases. Contrary to the long-standing assumption that SUMO has no role in proteolytic targeting and rather acts as an antagonist of ubiquitin in some cases, it has recently been discovered that sumoylation itself can function as a secondary signal mediating ubiquitin-dependent degradation by the proteasome. The discovery of a novel family of RING finger ubiquitin ligases bearing SUMO interaction motifs implicated the ubiquitin system in the control of SUMO modified proteins. SUMO modification as a signal for degradation is conserved in eukaryotes and ubiquitin ligases that specifically recognize SUMO-modified proteins have been discovered in species ranging from yeasts to humans. This chapter summarizes what is known about these ligases and their role in controlling sumoylated proteins.


Ubiquitin Ligase Schizosaccharomyces Pombe Sumo Modification Sumo Conjugation Sumo Specific Protease 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Hochstrasser M. Origin and function of ubiquitin-like proteins. Nature 2009; 458:422–429.PubMedCrossRefGoogle Scholar
  2. 2.
    Meluh PB, Koshland D. Evidence that the MIF2 gene of Saccharomyces cerevisiae encodes a centromere protein with homology to the mammalian centromere protein CENP-C. Mol Biol Cell 1995; 6:793–807.PubMedGoogle Scholar
  3. 3.
    Mannen H, Tseng HM, Cho CL et al. Cloning and expression of human homolog HSMT3 to yeast SMT3 suppressor of MIF2 mutations in a centromere protein gene. Biochem Biophys Res Commun 1996; 222:178–180.PubMedCrossRefGoogle Scholar
  4. 4.
    Johnson ES, Schwienhorst I, Dohmen RJ et al. The ubiquitin-like protein Smt3p is activated for conjugation to other proteins by an Aos1p/Uba2p heterodimer. EMBO J 1997; 16:5509–5519.PubMedCrossRefGoogle Scholar
  5. 5.
    Tanaka K, Nishide J, Okazaki K et al. Characterization of a fission yeast SUMO-1 homologue, pmt3p, required for multiple nuclear events, including the control of telomere length and chromosome segregation. Mol Cell Biol 1999; 19:8660–8672.PubMedGoogle Scholar
  6. 6.
    Nacerddine K, Lehembre F, Bhaumik M et al. The SUMO pathway is essential for nuclear integrity and chromosome segregation in mice. Dev Cell 2005; 9:769–779.PubMedCrossRefGoogle Scholar
  7. 7.
    Zhang FP, Mikkonen L, Toppari J et al. Sumo-1 function is dispensable in normal mouse development. Mol Cell Biol 2008; 28:5381–5390.PubMedCrossRefGoogle Scholar
  8. 8.
    Saitoh H, Hinchey J. Functional heterogeneity of small ubiquitin-related protein modifiers SUMO-1 versus SUMO-2/3. J Biol Chem 2000; 275:6252–6258.PubMedCrossRefGoogle Scholar
  9. 9.
    Golebiowski F, Matic I, Tatham MH et al. System-wide changes to SUMO modifications in response to heat shock. Sci Signal 2009; 2:ra24.PubMedCrossRefGoogle Scholar
  10. 10.
    Weisshaar SR, Keusekotten K, Krause A et al. Arsenic trioxide stimulates SUMO-2/3 modification leading to RNF4-dependent proteolytic targeting of PML. FEBS Lett 2008; 582:3174–3178.PubMedCrossRefGoogle Scholar
  11. 11.
    Johnson ES, Blobel G. Cell cycle-regulated attachment of the ubiquitin-related protein SUMO to the yeast septins. J Cell Biol 1999; 147:981–994.PubMedCrossRefGoogle Scholar
  12. 12.
    Bernier-Villamor V, Sampson DA, Matunis MJ et al. Structural basis for E2-mediated SUMO conjugation revealed by a complex between ubiquitin-conjugating enzyme Ubc9 and RanGAP1. Cell 2002; 108:345–356.PubMedCrossRefGoogle Scholar
  13. 13.
    Tatham MH, Jaffray E, Vaughan OA et al. Polymeric chains of SUMO-2 and SUMO-3 are conjugated to protein substrates by SAE1/SAE2 and Ubc9. J Biol Chem 2001; 276:35368–35374.PubMedCrossRefGoogle Scholar
  14. 14.
    Bylebyl GR, Belichenko I, Johnson ES. The SUMO isopeptidase Ulp2 prevents accumulation of SUMO chains in yeast. J Biol Chem 2003; 278:44112–44120.CrossRefGoogle Scholar
  15. 15.
    Ulrich HD. The fast-growing business of SUMO chains. Mol Cell 2008; 32:301–305.PubMedCrossRefGoogle Scholar
  16. 16.
    Matic I, van Hagen M, Schimmel J et al. In vivo identification of human SUMO polymerization sites by high accuracy mass spectrometry and an in-vitro to in vivo strategy. Mol Cell Proteomics 2007.Google Scholar
  17. 17.
    Muller S, Hoege C, Pyrowolakis G et al. SUMO, ubiquitin’s mysterious cousin. Nat Rev Mol Cell Biol 2001; 2:202–210.PubMedCrossRefGoogle Scholar
  18. 18.
    Seeler JS, Dejean A. Nuclear and unclear functions of SUMO. Nat Rev Mol Cell Biol 2003; 4:690–699.PubMedCrossRefGoogle Scholar
  19. 19.
    Johnson ES. Protein modification by SUMO. Annu Rev Biochem 2004; 73:355–382.PubMedCrossRefGoogle Scholar
  20. 20.
    Hay RT. SUMO: a history of modification. Mol Cell 2005; 18:1–12.PubMedCrossRefGoogle Scholar
  21. 21.
    Kim JH, Choi HJ, Kim B et al. Roles of sumoylation of a reptin chromatin-remodelling complex in cancer metastasis. Nat Cell Biol 2006; 8:631–639.PubMedCrossRefGoogle Scholar
  22. 22.
    Hoeller D, Hecker CM, Dikic I. Ubiquitin and ubiquitin-like proteins in cancer pathogenesis. Nat Rev Cancer 2006; 6:776–788.PubMedCrossRefGoogle Scholar
  23. 23.
    Geiss-Friedlander R, Melchior F. Concepts in sumoylation: a decade on. Nat Rev Mol Cell Biol 2007; 8:947–956.PubMedCrossRefGoogle Scholar
  24. 24.
    Bischof O, Dejean A. SUMO is growing senescent. Cell Cycle 2007; 6:677–681.PubMedGoogle Scholar
  25. 25.
    Seeler JS, Bischof O, Nacerddine K et al. SUMO, the three Rs and cancer. Curr Top Microbiol Immunol 2007; 313:49–71.PubMedCrossRefGoogle Scholar
  26. 26.
    Bergink S, Jentsch S. Principles of ubiquitin and SUMO modifications in DNA repair. Nature 2009; 458:461–467.PubMedCrossRefGoogle Scholar
  27. 27.
    Dohmen RJ. SUMO protein modification. Biochim Biophys Acta 2004; 1695:113–131.PubMedGoogle Scholar
  28. 28.
    Desterro JM, Rodriguez MS, Hay RT. SUMO-1 modification of IkappaBalpha inhibits NF-kappaB activation. Mol Cell 1998; 2:233–239.PubMedCrossRefGoogle Scholar
  29. 29.
    Skaug B, Jiang X, Chen ZJ. The role of ubiquitin in NF-kappaB regulatory pathways. Annu Rev Biochem 2009; 78:769–796.PubMedCrossRefGoogle Scholar
  30. 30.
    Ulrich HD. Mutual interactions between the SUMO and ubiquitin systems: a plea of no contest. Trends Cell Biol 2005; 15:525–532.PubMedCrossRefGoogle Scholar
  31. 31.
    Hoege C, Pfander B, Moldovan GL et al. RAD6-dependent DNA repair is linked to modification of PCNA by ubiquitin and SUMO. Nature 2002; 419:135–141.PubMedCrossRefGoogle Scholar
  32. 32.
    Ulrich HD, Jentsch S. Two RING finger proteins mediate cooperation between ubiquitin-conjugating enzymes in DNA repair. EMBO J 2000; 19:3388–3397.PubMedCrossRefGoogle Scholar
  33. 33.
    Sun H, Leverson JD, Hunter T. Conserved function of RNF4 family proteins in eukaryotes: targeting a ubiquitin ligase to SUMOylated proteins. EMBO J 2007; 26:4102–112.PubMedCrossRefGoogle Scholar
  34. 34.
    Pfander B, Moldovan GL, Sacher M et al. SUMO-modified PCNA recruits Srs2 to prevent recombination during S phase. Nature 2005; 436:428–433.PubMedGoogle Scholar
  35. 35.
    Papouli E, Chen S, Davies AA et al. Crosstalk between SUMO and ubiquitin on PCNA is mediated by recruitment of the helicase Srs2p. Mol Cell 2005; 19:123–133.PubMedCrossRefGoogle Scholar
  36. 36.
    Uzunova K, Gottsche K, Miteva M et al. Ubiquitin-dependent proteolytic control of SUMO conjugates. J Biol Chem 2007; 282:34167–34175.PubMedCrossRefGoogle Scholar
  37. 37.
    Xie Y, Kerscher O, Kroetz MB et al. The yeast HEX3-SLX8 heterodimer is a ubiquitin ligase stimulated by substrate sumoylation. J Biol Chem 2007.Google Scholar
  38. 38.
    Mullen JR, Brill SJ. Activation of the Slx5-Slx8 ubiquitin ligase by poly-small ubiquitin-like modifier conjugates. J Biol Chem 2008; 283:19912–19921.PubMedCrossRefGoogle Scholar
  39. 39.
    Prudden J, Pebernard S, Raffa G et al. SUMO-targeted ubiquitin ligases in genome stability. EMBO J 2007; 26:4089–4101.PubMedCrossRefGoogle Scholar
  40. 40.
    Cheng J, Kang X, Zhang S et al. SUMO-specific protease 1 is essential for stabilization of HIF1alpha during hypoxia. Cell 2007; 131:584–595.PubMedCrossRefGoogle Scholar
  41. 41.
    Mahajan R, Delphin C, Guan T et al. A small ubiquitin-related polypeptide involved in targeting RanGAP1 to nuclear pore complex protein RanBP2. Cell 1997; 88:97–107.PubMedCrossRefGoogle Scholar
  42. 42.
    Saitoh H, Pu R, Cavenagh M et al. RanBP2 associates with Ubc9p and a modified form of RanGAP1. Proc Natl Acad Sci USA 1997; 94:3736–3741.PubMedCrossRefGoogle Scholar
  43. 43.
    Matunis MJ, Wu J, Blobel G. SUMO-1 modification and its role in targeting the Ran GTPase-activating protein, RanGAP1, to the nuclear pore complex. J Cell Biol 1998; 140:499–509.PubMedCrossRefGoogle Scholar
  44. 44.
    Song J, Durrin LK, Wilkinson TA et al. Identification of a SUMO-binding motif that recognizes SUMO-modified proteins. Proc Natl Acad Sci USA 2004; 101:14373–14378.PubMedCrossRefGoogle Scholar
  45. 45.
    Shen TH, Lin HK, Scaglioni PP et al. The mechanisms of PML-nuclear body formation. Mol Cell 2006; 24:331–339.PubMedCrossRefGoogle Scholar
  46. 46.
    Lin DY, Huang YS, Jeng JC et al. Role of SUMO-interacting motif in Daxx SUMO modification, subnuclear localization and repression of sumoylated transcription factors. Mol Cell 2006; 24:341–354.PubMedCrossRefGoogle Scholar
  47. 47.
    Kerscher O. SUMO junction-what’s your function? New insights through SUMO-interacting motifs. EMBO Rep 2007; 8:550–555.PubMedCrossRefGoogle Scholar
  48. 48.
    Hardeland U, Steinacher R, Jiricny J et al. Modification of the human thymine-D NA glycosylase by ubiquitin-like proteins facilitates enzymatic turnover. EMBO J 2002; 21:1456–1464.PubMedCrossRefGoogle Scholar
  49. 49.
    Steinacher R, Schar P. Functionality of human thymine DNA glycosylase requires SUMO-regulated changes in protein conformation. Curr Biol 2005; 15:616–623.PubMedCrossRefGoogle Scholar
  50. 50.
    Hay RT. SUMO-specific proteases: a twist in the tail. Trends Cell Biol 2007; 17:370–376.PubMedCrossRefGoogle Scholar
  51. 51.
    Mukhopadhyay D, Dasso M. Modification in reverse: the SUMO proteases. Trends Biochem Sci 2007; 32:286–295.PubMedCrossRefGoogle Scholar
  52. 52.
    Li SJ, Hochstrasser M. A new protease required for cell-cycle progression in yeast. Nature 1999; 398:246–251.PubMedCrossRefGoogle Scholar
  53. 53.
    Li SJ, Hochstrasser M. The yeast ULP2 (SMT4) gene encodes a novel protease specific for the ubiquitin-like Smt3 protein. Mol Cell Biol 2000; 20:2367–2377.PubMedCrossRefGoogle Scholar
  54. 54.
    Schwienhorst I, Johnson ES, Dohmen RJ. SUMO conjugation and deconjugation. Mol Gen Genet 2000; 263:771–786.PubMedCrossRefGoogle Scholar
  55. 55.
    Xu Z, Chan HY, Lam WL et al. SUMO Proteases: Redox Regulation and Biological Consequences. Antioxid Redox Signal 2009; 11:1453–1484.PubMedCrossRefGoogle Scholar
  56. 56.
    Mukhopadhyay D, Ayaydin F, Kolli N et al. SUSP1 antagonizes formation of highly SUMO2/3-conjugated species. J Cell Biol 2006; 174:939–949.PubMedCrossRefGoogle Scholar
  57. 57.
    Hofmann K. Ubiquitin-binding domains and their role in the DNA damage response. DNA Repair (Amst) 2009; 8:544–556.CrossRefGoogle Scholar
  58. 58.
    Minty A, Dumont X, Kaghad M et al. Covalent modification of p73alpha by SUMO-1. Two-hybrid screening with p73 identifies novel SUMO-1-interacting proteins and a SUMO-1 interaction motif. J Biol Chem 2000; 275:36316–36323.PubMedCrossRefGoogle Scholar
  59. 59.
    Song J, Zhang Z, Hu W et al. Small ubiquitin-like modifier (SUMO) recognition of a SUMO binding motif: a reversal of the bound orientation. J Biol Chem 2005; 280:40122–40129.PubMedCrossRefGoogle Scholar
  60. 60.
    Hannich JT, Lewis A, Kroetz MB et al. Defining the SUMO-modified proteome by multiple approaches in Saccharomyces cerevisiae. J Biol Chem 2005; 280:4102–4110.PubMedCrossRefGoogle Scholar
  61. 61.
    Hecker CM, Rabiller M, Haglund K et al. Specification of SUMO1-and SUMO2-interacting motifs. J Biol Chem 2006; 281:16117–16127.PubMedCrossRefGoogle Scholar
  62. 62.
    Sekiyama N, Ikegami T, Yamane T et al. Structure of the small ubiquitin-like modifier (SUMO)-interacting motif of MBD1-containing chromatin-associated factor 1 bound to SUMO-3. J Biol Chem 2008; 283:35966–35975.PubMedCrossRefGoogle Scholar
  63. 63.
    Reverter D, Lima CD. Insights into E3 ligase activity revealed by a SUMO-RanGAP1-Ubc9-Nup358 complex. Nature 2005; 435:687–692.PubMedCrossRefGoogle Scholar
  64. 64.
    Stehmeier P, Muller S. Phospho-regulated SUMO interaction modules connect the SUMO system to CK2 signaling. Mol Cell 2009; 33:400–409.PubMedCrossRefGoogle Scholar
  65. 65.
    Hershko A, Ciechanover A. The ubiquitin system. Annu Rev Biochem 1998; 67:425–479.PubMedCrossRefGoogle Scholar
  66. 66.
    Varshavsky A. Regulated protein degradation. Trends Biochem Sci 2005; 30:283–286.PubMedCrossRefGoogle Scholar
  67. 67.
    Weissman AM. Themes and variations on ubiquitylation. Nat Rev Mol Cell Biol 2001; 2:169–178.PubMedCrossRefGoogle Scholar
  68. 68.
    Joazeiro CA, Weissman AM. RING finger proteins: mediators of ubiquitin ligase activity. Cell 2000; 102:549–552.PubMedCrossRefGoogle Scholar
  69. 69.
    Wang Z, Prelich G. Quality control of a transcriptional regulator by SUMO-targeted degradation. Mol Cell Biol 2009; 29:1694–1706.PubMedCrossRefGoogle Scholar
  70. 70.
    Uetz P, Giot L, Cagney G et al. A comprehensive analysis of protein-protein interactions in Saccharomyces cerevisiae. Nature 2000; 403:623–627.PubMedCrossRefGoogle Scholar
  71. 71.
    Ito T, Chiba T, Ozawa R et al. A comprehensive two-hybrid analysis to explore the yeast protein interactome. Proc Natl Acad Sci USA 2001; 98:4569–4574.PubMedCrossRefGoogle Scholar
  72. 72.
    Wang Z, Jones GM, Prelich G. Genetic analysis connects SLX5 and SLX8 to the SUMO pathway in Saccharomyces cerevisiae. Genetics 2006; 172:1499–1509.PubMedCrossRefGoogle Scholar
  73. 73.
    Mullen JR, Kaliraman V, Ibrahim SS et al. Requirement for three novel protein complexes in the absence of the Sgs1 DNA helicase in Saccharomyces cerevisiae. Genetics 2001; 157:103–118.PubMedGoogle Scholar
  74. 74.
    Cobb JA, Bjergbaek L. RecQ helicases: lessons from model organisms. Nucleic Acids Res 2006; 34:4106–4114.PubMedCrossRefGoogle Scholar
  75. 75.
    Pan X, Ye P, Yuan DS et al. A DNA integrity network in the yeast Saccharomyces cerevisiae. Cell 2006; 124:1069–1081.PubMedCrossRefGoogle Scholar
  76. 76.
    Collins SR, Miller KM, Maas NL et al. Functional dissection of protein complexes involved in yeast chromosome biology using a genetic interaction map. Nature 2007; 446:806–810.PubMedCrossRefGoogle Scholar
  77. 77.
    Ulrich HD. PCNASUMO and Srs2: a model SUMO substrate-effector pair. Biochem Soc Trans 2007; 35:1385–1388.PubMedCrossRefGoogle Scholar
  78. 78.
    Watts FZ. Sumoylation of PCNA: Wrestling with recombination at stalled replication forks. DNA Repair (Amst) 2006; 5:399–403.CrossRefGoogle Scholar
  79. 79.
    Soustelle C, Vernis L, Freon K et al. A new Saccharomyces cerevisiae strain with a mutant Smt3-deconjugating Ulp1 protein is affected in DNA replication and requires Srs2 and homologous recombination for its viability. Mol Cell Biol 2004; 24:5130–5143.PubMedCrossRefGoogle Scholar
  80. 80.
    Azam M, Lee JY, Abraham V et al. Evidence that the S.cerevisiae Sgs1 protein facilitates recombinational repair of telomeres during senescence. Nucleic Acids Res 2006; 34:506–516.PubMedCrossRefGoogle Scholar
  81. 81.
    Zhang C, Roberts TM, Yang J et al. Suppression of genomic instability by SLX5 and SLX8 in Saccharomyces cerevisiae. DNA Repair (Amst) 2006; 5:336–346.CrossRefGoogle Scholar
  82. 82.
    Burgess RC, Rahman S, Lisby M et al. The Slx5-Slx8 complex affects sumoylation of DNA repair proteins and negatively regulates recombination. Mol Cell Biol 2007; 27:6153–6162.PubMedCrossRefGoogle Scholar
  83. 83.
    Takahashi Y, Dulev S, Liu X et al. Cooperation of sumoylated chromosomal proteins in rDNA maintenance. PLoS Genet 2008; 4:e1000215.PubMedCrossRefGoogle Scholar
  84. 84.
    Putnam CD, Hayes TK, Kolodner RD. Specific pathways prevent duplication-mediated genome rearrangements. Nature 2009; 460:984–989.PubMedCrossRefGoogle Scholar
  85. 85.
    Rouse J. Control of genome stability by SLX protein complexes. Biochem Soc Trans 2009; 37:495–510.PubMedCrossRefGoogle Scholar
  86. 86.
    Heideker J, Perry JJ, Boddy MN. Genome stability roles of SUMO-targeted ubiquitin ligases. DNA Repair (Amst) 2009; 8:517–524.CrossRefGoogle Scholar
  87. 87.
    Cook CE, Hochstrasser M, Kerscher O. The SUMO-targeted ubiquitin ligase subunit Slx5 resides in nuclear foci and at sites of DNA breaks. Cell Cycle 2009; 8:1080–1089.PubMedGoogle Scholar
  88. 88.
    Nagai S, Dubrana K, Tsai-Pflugfelder M et al. Functional targeting of DNA damage to a nuclear pore-associated SUMO-dependent ubiquitin ligase. Science 2008; 322:597–602.PubMedCrossRefGoogle Scholar
  89. 89.
    Yang L, Mullen JR, Brill SJ. Purification of the yeast Slx5-Slx8 protein complex and characterization of its DNA-binding activity. Nucleic Acids Res 2006; 34:5541–5551.PubMedCrossRefGoogle Scholar
  90. 90.
    Zhang Z, Buchman AR. Identification of a member of a DNA-dependent ATPase family that causes interference with silencing. Mol Cell Biol 1997; 17:5461–5472.PubMedGoogle Scholar
  91. 91.
    Shirai C, Mizuta K. SUMO mediates interaction of Ebp2p, the yeast homolog of Epstein-Barr virus nuclear antigen 1-binding protein 2, with a RING finger protein Ris1p. Biosci Biotechnol Biochem 2008; 72:1881–1886.PubMedCrossRefGoogle Scholar
  92. 92.
    Novatchkova M, Bachmair A, Eisenhaber B et al. Proteins with two SUMO-like domains in chromatin-associated complexes: the RENi (Rad60-E sc2-NIP45) family. BMC Bioinformatics 2005; 6:22.PubMedCrossRefGoogle Scholar
  93. 93.
    Prudden J, Perry JJ, Arvai AS et al. Molecular mimicry of SUMO promotes DNA repair. Nat Struct Mol Biol 2009; 16:509–516.PubMedCrossRefGoogle Scholar
  94. 94.
    Häkli M, Lorick KL, Weissman AM et al. Transcriptional coregulator SNURF (RNF4) possesses ubiquitin E3 ligase activity. FEBS Lett 2004; 560:56–62.PubMedCrossRefGoogle Scholar
  95. 95.
    Kosoy A, Calonge TM, Outwin EA et al. Fission yeast rnf4 homologs are required for DNA repair. J Biol Chem 2007; 282:20388–20394.PubMedCrossRefGoogle Scholar
  96. 96.
    Tatham MH, Geoffroy MC, Shen L et al. RNF4 is a poly-SUMO-specific E3 ubiquitin ligase required for arsenic-induced PML degradation. Nat Cell Biol 2008; 10:538–546.PubMedCrossRefGoogle Scholar
  97. 97.
    Häkli M, Karvonen U, Janne OA et al. SUMO-1 promotes association of SNURF (RNF4) with PML nuclear bodies. Exp Cell Res 2005; 304:224–233.PubMedCrossRefGoogle Scholar
  98. 98.
    Muller S, Matunis MJ, Dejean A. Conjugation with the ubiquitin-related modifier SUMO-1 regulates the partitioning of PML within the nucleus. EMBO J 1998; 17:61–70.PubMedCrossRefGoogle Scholar
  99. 99.
    Ishov AM, Sotnikov AG, Negorev D et al. 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 1999; 147:221–234.PubMedCrossRefGoogle Scholar
  100. 100.
    Zhong S, Muller S, Ronchetti S et al. Role of SUMO-1-modified PML in nuclear body formation. Blood 2000; 95:2748–2752.PubMedGoogle Scholar
  101. 101.
    Bernardi R, Pandolfi PP. Structure, dynamics and functions of promyelocytic leukaemia nuclear bodies. Nat Rev Mol Cell Biol 2007; 8:1006–1016.PubMedCrossRefGoogle Scholar
  102. 102.
    Nisole S, Stoye JP, Saib A. TRIM family proteins: retroviral restriction and antiviral defence. Nat Rev Microbiol 2005; 3:799–808.PubMedCrossRefGoogle Scholar
  103. 103.
    de The H, Chomienne C, Lanotte M et al. The t(15;17) translocation of acute promyelocytic leukaemia fuses the retinoic acid receptor alpha gene to a novel transcribed locus. Nature 1990; 347:558–561.PubMedCrossRefGoogle Scholar
  104. 104.
    Kakizuka A, Miller WH Jr, Umesono K et al. Chromosomal translocation t(15;17) in human acute promyelocytic leukemia fuses RAR alpha with a novel putative transcription factor, PML. Cell 1991; 66:663–674.PubMedCrossRefGoogle Scholar
  105. 105.
    Wang ZY, Chen Z. Acute promyelocytic leukemia: from highly fatal to highly curable. Blood 2008; 111:2505–515.PubMedCrossRefGoogle Scholar
  106. 106.
    Lallemand-Breitenbach V, Zhu J, Puvion F et al. 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 2001; 193:1361–1371.PubMedCrossRefGoogle Scholar
  107. 107.
    Lallemand-Breitenbach V, Jeanne M, Benhenda S et al. Arsenic degrades PML or PML-RARalpha through a SUMO-triggered RNF4/ubiquitin-mediated pathway. Nat Cell Biol 2008; 10:547–555.PubMedCrossRefGoogle Scholar
  108. 108.
    Bossis G, Melchior F. Regulation of SUMOylation by Reversible Oxidation of SUMO Conjugating Enzymes. Mol Cell 2006; 21:349–357.PubMedCrossRefGoogle Scholar
  109. 109.
    Hayakawa F, Privalsky ML. Phosphorylation of PML by mitogen-activated protein kinases plays a key role in arsenic trioxide-mediated apoptosis. Cancer Cell 2004; 5:389–401.PubMedCrossRefGoogle Scholar
  110. 110.
    Scaglioni PP, Yung TM, Choi SC et al. CK2 mediates phosphorylation and ubiquitin-mediated degradation of the PML tumor suppressor. Mol Cell Biochem 2008; 316:149–154.PubMedCrossRefGoogle Scholar
  111. 111.
    Percherancier Y, Germain-D esprez D, Galisson F et al. Role of SUMO in RNF4-mediated promyelocytic leukemia protein (PML) degradation: sumoylation of PML and phospho-switch control of its SUMO binding domain dissected in living cells. J Biol Chem 2009; 284:16595–16608.PubMedCrossRefGoogle Scholar
  112. 112.
    Knipscheer P, Flotho A, Klug H et al. Ubc9 sumoylation regulates SUMO target discrimination. Mol Cell 2008; 31:371–382.PubMedCrossRefGoogle Scholar
  113. 113.
    Meulmeester E, Kunze M, Hsiao HH et al. Mechanism and consequences for paralog-specific sumoylation of ubiquitin-specific protease 25. Mol Cell 2008; 30:610–619.PubMedCrossRefGoogle Scholar
  114. 114.
    Cho G, Lim Y, Golden JA. SUMO interaction motifs in Sizn1 are required for promyelocytic leukemia protein nuclear body localization and for transcriptional activation. J Biol Chem 2009; 284:19592–19600.PubMedCrossRefGoogle Scholar
  115. 115.
    Hoeller D, Crosetto N, Blagoev B et al. Regulation of ubiquitin-binding proteins by monoubiquitination. Nat Cell Biol 2006; 8:163–169.PubMedCrossRefGoogle Scholar
  116. 116.
    Ito K, Bernardi R, Morotti A et al. PML targeting eradicates quiescent leukaemia-initiating cells. Nature 2008; 453:1072–1078.PubMedCrossRefGoogle Scholar
  117. 117.
    Bae SH, Jeong JW, Park JA et al. Sumoylation increases HIF-1alpha stability and its transcriptional activity. Biochem Biophys Res Commun 2004; 324:394–400.PubMedCrossRefGoogle Scholar
  118. 118.
    Carbia-Nagashima A, Gerez J, Perez-Castro C et al. RSUME, a Small RWD-Containing Protein, Enhances SUMO Conjugation and Stabilizes HIF-1alpha during Hypoxia. Cell 2007; 131:309–323.PubMedCrossRefGoogle Scholar
  119. 119.
    Geoffroy MC, Hay RT. An additional role for SUMO in ubiquitin-mediated proteolysis. Nat Rev Mol Cell Biol 2009; 10:564–568.PubMedCrossRefGoogle Scholar
  120. 120.
    Salghetti SE, Caudy AA, Chenoweth JG et al. Regulation of transcriptional activation domain function by ubiquitin. Science 2001; 293:1651–1653.PubMedCrossRefGoogle Scholar
  121. 121.
    Conaway RC, Brower CS, Conaway JW. Emerging roles of ubiquitin in transcription regulation. Science 2002; 296:1254–1258.PubMedCrossRefGoogle Scholar
  122. 122.
    Hunter T. The age of crosstalk: phosphorylation, ubiquitination and beyond. Mol Cell 2007; 28:730–738.PubMedCrossRefGoogle Scholar

Copyright information

© Landes Bioscience and Springer Science+Business Media 2010

Authors and Affiliations

  • Maria Miteva
    • 3
  • Kirstin Keusekotten
    • 1
  • Kay Hofmann
    • 2
  • Gerrit J. K. Praefcke
    • 1
  • R. Jürgen Dohmen
    • 3
  1. 1.Center for Molecular Medicine Cologne (CMMC), Institute for GeneticsCologne UniversityCologneGermany
  2. 2.Bioinformatics GroupMiltenyi Biotec GmbHBergisch-GladbachGermany
  3. 3.Institute for GeneticsCologne UniversityCologneGermany

Personalised recommendations