• 1
    Watts, F. Z. (2013) Starting and stopping SUMOylation: What regulates the regulator?, Chromosoma. 451463.
  • 2
    Wilson, V. G. (2012) Sumoylation at the host-pathogen interface. Biomolecules 2, 203227.
  • 3
    Everett, R. D., Boutell, C., and Hale, B. G. (2013) Interplay between viruses and host sumoylation pathways. Nat. Rev. Microbiol. 11, 400411.
  • 4
    Mattoscio, D., Segre C. V., and Chiocca S. (2013) Viral manipulation of cellular protein conjugation pathways: The SUMO lesson. World J. Virol. 2. 7990.
  • 5
    Matunis, M. J., Coutavas, E., and Blobel, G. (1996) A novel ubiquitin-like modification modulates the partitioning of the Ran-GTPase-activating protein RanGAP1 between the cytosol and the nuclear pore complex. J. Cell Biol. 135, 14571470.
  • 6
    Mahajan, R., Delphin, C., Guan, T., Gerace, L., and Melchior, F. (1997) A small ubiquitin-related polypeptide involved in targeting RanGAP1 to nuclear pore complex protein RanBP2. Cell. 88, 97107.
  • 7
    Bohren, K. M., Nadkarni, V., Song, J. H., Gabbay, K. H., and Owerbach, D. (2004) A M55V polymorphism in a novel SUMO gene (SUMO-4) differentially activates heat shock transcription factors and is associated with susceptibility to type I diabetes mellitus. J. Biol. Chem. 279, 2723327238.
  • 8
    Citro, S. and Chiocca, S. (2013) Sumo paralogs: Redundancy and divergencies. Front. Biosci. 5, 544553.
  • 9
    Tatham, M. H., Jaffray, E., Vaughan, O. A., Desterro, J. M., Botting, C. H., et al. (2001) Polymeric chains of SUMO-2 and SUMO-3 are conjugated to protein substrates by SAE1/SAE2 and Ubc9. J. Biol. Chem. 276, 3536835374.
  • 10
    Matic, I., van Hagen, M., Schimmel, J., Macek, B., Ogg, S. C., et al. (2008) In vivo identification of human small ubiquitin-like modifier polymerization sites by high accuracy mass spectrometry and an in vitro to in vivo strategy. Mol. Cell. Proteomics 7, 132144.
  • 11
    Hateboer, G., Hijmans, E. M., Nooij, J. B., Schlenker, S., Jentsch, S., et al. (1996) mUBC9, a novel adenovirus E1A-interacting protein that complements a yeast cell cycle defect. J. Biol. Chem. 271, 2590625911.
  • 12
    Seufert, W., Futcher, B., and Jentsch, S. (1995) Role of a ubiquitin-conjugating enzyme in degradation of S- and M-phase cyclins. Nature. 373, 7881.
  • 13
    al-Khodairy, F., Enoch, T., Hagan, I. M., and Carr, A. M. (1995) The Schizosaccharomyces pombe hus5 gene encodes a ubiquitin conjugating enzyme required for normal mitosis. J. Cell Sci. 108 (Pt 2), 475486.
  • 14
    van Wijk, S. J. and Timmers, H. T. (2010) The family of ubiquitin-conjugating enzymes (E2s): Deciding between life and death of proteins. FASEB J. 24, 981993.
  • 15
    Jentsch, S. (1992) The ubiquitin-conjugation system. Annu. Rev. Genet. 26, 179207.
  • 16
    Mo, Y. Y. and Moschos, S. J. (2005) Targeting Ubc9 for cancer therapy. Expert Opin. Ther.Ttargets 9, 12031216.
  • 17
    Nacerddine, K., Lehembre, F., Bhaumik, M., Artus, J., Cohen-Tannoudji, M., et al. (2005) The SUMO pathway is essential for nuclear integrity and chromosome segregation in mice. Dev. Cell. 9, 769779.
  • 18
    Nowak, M. and Hammerschmidt, M. (2006) Ubc9 regulates mitosis and cell survival during zebrafish development. Mol. Biol. Cell. 17, 53245336.
  • 19
    Jones, D., Crowe, E., Stevens, T.A., and Candido, E.P. (2002) Functional and phylogenetic analysis of the ubiquitylation system in Caenorhabditis elegans: Ubiquitin-conjugating enzymes, ubiquitin-activating enzymes, and ubiquitin-like proteins. Genome Biol. 3, RESEARCH0002.
  • 20
    Duan, X., Trent, J.O., and Ye, H. (2009) Targeting the SUMO E2 conjugating enzyme Ubc9 interaction for anti-cancer drug design. Anticancer Agents Med. Chem. 9, 5154.
  • 21
    Tatham, M. H., Kim, S., Yu, B., Jaffray, E., Song, J., et al. (2003) Role of an N-terminal site of Ubc9 in SUMO-1, −2, and −3 binding and conjugation. Biochemistry 42, 99599969.
  • 22
    Hay, R. T. (2007) SUMO-specific proteases: A twist in the tail. Trends Cell Biol. 17, 370376.
  • 23
    Tong, H., Hateboer, G., Perrakis, A., Bernards, R., and Sixma, T.K. (1997) Crystal structure of murine/human Ubc9 provides insight into the variability of the ubiquitin-conjugating system. J. Biol. Chem. 272, 2138121387.
  • 24
    Bernier-Villamor, V., Sampson, D. A., Matunis, M. J., and Lima, C. D. (2002) Structural basis for E2-mediated SUMO conjugation revealed by a complex between ubiquitin-conjugating enzyme Ubc9 and RanGAP1. Cell 108, 345356.
  • 25
    Wang, J., Hu, W., Cai, S., Lee, B., Song, J., et al. (2007) The intrinsic affinity between E2 and the Cys domain of E1 in ubiquitin-like modifications. Mol. Cell. 27, 228237.
  • 26
    Melchior, F., Schergaut, M., and Pichler, A. (2003) SUMO: Ligases, isopeptidases and nuclear pores. Trends Biochem. Sci. 28, 612618.
  • 27
    Knipscheer, P., van Dijk, W. J., Olsen, J. V., Mann, M., and Sixma, T. K. (2007) Noncovalent interaction between Ubc9 and SUMO promotes SUMO chain formation. EMBO J. 26, 27972807.
  • 28
    Rodriguez, M. S., Dargemont, C., and Hay, R. T. (2001) SUMO-1 conjugation in vivo requires both a consensus modification motif and nuclear targeting. J. Biol. Chem. 276, 1265412659.
  • 29
    Hietakangas, V., Anckar, J., Blomster, H. A., Fujimoto, M., Palvimo, J. J., et al. (2006) PDSM, a motif for phosphorylation-dependent SUMO modification. Proc. Natl. Acad. Sci. USA 103, 4550.
  • 30
    Yang, S. H., Galanis, A., Witty, J., and Sharrocks, A. D. (2006) An extended consensus motif enhances the specificity of substrate modification by SUMO. EMBO J. 25, 50835093.
  • 31
    Lin, D. Y., Huang, Y. S., Jeng, J. C., Kuo, H. Y., Chang, C. C., et al. (2006) Role of SUMO-interacting motif in Daxx SUMO modification, subnuclear localization, and repression of sumoylated transcription factors. Mol. Cell 24, 341354.
  • 32
    Danielsen, J. R., Povlsen, L. K., Villumsen, B. H., Streicher, W., Nilsson, J., et al. (2012) DNA damage-inducible SUMOylation of HERC2 promotes RNF8 binding via a novel SUMO-binding Zinc finger. J. Cell Biol. 197, 179187.
  • 33
    Pilla, E., Moller, U., Sauer, G., Mattiroli, F., Melchior, F., et al. (2012) A novel SUMO1-specific interacting motif in dipeptidyl peptidase 9 (DPP9) that is important for enzymatic regulation. J. Biol. Chem. 287, 4432044329.
  • 34
    Shin, E. J., Shin, H. M., Nam, E., Kim, W. S., Kim, J. H., et al. (2012) DeSUMOylating isopeptidase: A second class of SUMO protease. EMBO Rep. 13, 339346.
  • 35
    Schulz, S., Chachami, G., Kozaczkiewicz, L., Winter, U., Stankovic-Valentin, N., et al. (2012) Ubiquitin-specific protease-like 1 (USPL1) is a SUMO isopeptidase with essential, non-catalytic functions. EMBO Rep. 13, 930938.
  • 36
    Zhu, S., Zhang, H., and Matunis, M. J. (2006) SUMO modification through rapamycin-mediated heterodimerization reveals a dual role for Ubc9 in targeting RanGAP1 to nuclear pore complexes. Exp. Cell Res. 312, 10421049.
  • 37
    Werner, A., Flotho, A., and Melchior, F. (2012) The RanBP2/RanGAP1*SUMO1/Ubc9 complex is a multisubunit SUMO E3 ligase. Mol. Cell. 46, 287298.
  • 38
    Klug, H., Xaver, M., Chaugule, V.K., Koidl, S., Mittler, G., et al. (2013) Ubc9 sumoylation controls SUMO chain formation and meiotic synapsis in Saccharomyces cerevisiae. Mol. Cell 50, 625636.
  • 39
    Kurtzman, A. L. and Schechter, N. (2001) Ubc9 interacts with a nuclear localization signal and mediates nuclear localization of the paired-like homeobox protein Vsx-1 independent of SUMO-1 modification. Proc. Natl. Acad. Sci. USA 98, 56025607.
  • 40
    Liu, L. B., Omata, W., Kojima, I., and Shibata, H. (2007) The SUMO conjugating enzyme Ubc9 is a regulator of GLUT4 turnover and targeting to the insulin-responsive storage compartment in 3T3-L1 adipocytes. Diabetes 56, 19771985.
  • 41
    Kurihara, I., Shibata, H., Kobayashi, S., Suda, N., Ikeda, Y., et al. (2005) Ubc9 and Protein Inhibitor of Activated STAT 1 activate chicken ovalbumin upstream promoter-transcription factor i-mediated human CYP11B2 gene transcription. J. Biol. Chem. 280, 67216730.
  • 42
    Uemura, A., Taniguchi, M., Matsuo, Y., Oku, M., Wakabayashi, S., et al. (2013) UBC9 regulates the stability of XBP1, a key transcription factor controlling the ER stress response. Cell Struct. Funct. 38, 6779.
  • 43
    Zhu, S., Sachdeva, M., Wu, F., Lu, Z., and Mo, Y. Y. (2010) Ubc9 promotes breast cell invasion and metastasis in a sumoylation-independent manner. Oncogene 29, 17631772.
  • 44
    Knipscheer, P., Flotho, A., Klug, H., Olsen, J. V., van Dijk, W. J., et al. (2008) Ubc9 sumoylation regulates SUMO target discrimination. Mol. Cell. 31, 371382.
  • 45
    Becker, J., Barysch, S. V., Karaca, S., Dittner, C., Hsiao, H. H., et al. (2013) Detecting endogenous SUMO targets in mammalian cells and tissues. Nat. Struct. Mol. Biol. 20, 525531.
  • 46
    Citro, S., Jaffray, E., Hay, R.T., Seiser, C., and Chiocca, S. (2013) A role for paralog-specific sumoylation in histone deacetylase 1 stability. J. Mol. Cell Biol. 416427.
  • 47
    Hsieh, Y. L., Kuo, H. Y., Chang, C. C., Naik, M. T., Liao, P. H., et al. (2013) Ubc9 acetylation modulates distinct SUMO target modification and hypoxia response. EMBO J. 32, 791804.
  • 48
    Su, Y. F., Yang, T., Huang, H., Liu, L.F., and Hwang, J. (2012) Phosphorylation of Ubc9 by Cdk1 enhances SUMOylation activity. PloS One. 7, e34250.
  • 49
    Tomasi, M. L., Tomasi, I., Ramani, K., Pascale, R. M., Xu, J., et al. (2012) S-adenosyl methionine regulates ubiquitin-conjugating enzyme 9 protein expression and sumoylation in murine liver and human cancers. Hepatology 56, 982993.
  • 50
    Bossis, G. and Melchior, F. (2006) Regulation of SUMOylation by reversible oxidation of SUMO conjugating enzymes. Mol. Cell. 21, 349357.
  • 51
    Ying, S., Dunnebier, T., Si, J., and Hamann, U. (2013) Estrogen receptor alpha and nuclear factor Y coordinately regulate the transcription of the SUMO-conjugating UBC9 gene in MCF-7 breast cancer cells. PloS One. 8, e75695.
  • 52
    Wu, F., Zhu, S., Ding, Y., Beck, W. T., and Mo, Y. Y. (2009) MicroRNA-mediated regulation of Ubc9 expression in cancer cells. Clin. Cancer Res. 15, 15501557.
  • 53
    Yu, F., Deng, H., Yao, H., Liu, Q., Su, F., et al. (2010) Mir-30 reduction maintains self-renewal and inhibits apoptosis in breast tumor-initiating cells. Oncogene 29, 41944204.
  • 54
    Lee, Y. J., Johnson, K. R., and Hallenbeck, J. M. (2012) Global protein conjugation by ubiquitin-like-modifiers during ischemic stress is regulated by microRNAs and confers robust tolerance to ischemia. PloS One. 7, e47787.
  • 55
    Zhao, Z., Tan, X., Zhao, A., Zhu, L., Yin, B., et al. (2012) microRNA-214-mediated UBC9 expression in glioma. BMB Rep. 45, 641646.
  • 56
    Glotzer, J. B., Saltik, M., Chiocca, S., Michou, A. I., Moseley, P., et al. (2000) Activation of heat-shock response by an adenovirus is essential for virus replication. Nature 407, 207211.
  • 57
    Boggio, R., Colombo, R., Hay, R. T., Draetta, G. F., and Chiocca, S. (2004) A mechanism for inhibiting the SUMO pathway. Mol. Cell. 16, 549561.
  • 58
    Boggio, R., Passafaro, A., and Chiocca, S. (2007) Targeting SUMO E1 to ubiquitin ligases: A viral strategy to counteract sumoylation. J. Biol. Chem. 282, 1537615382.
  • 59
    Colombo, R., Boggio, R., Seiser, C., Draetta, G. F., and Chiocca, S. (2002) The adenovirus protein Gam1 interferes with sumoylation of histone deacetylase 1. EMBO Rep. 3, 10621068.
  • 60
    Heaton, P. R., Deyrieux, A. F., Bian, X. L., and Wilson, V. G. (2011) HPV E6 proteins target Ubc9, the SUMO conjugating enzyme. Virus Res. 158, 199208.
  • 61
    Gomes, R., Guerra-Sa, R., and Arruda, E. (2010) Coxsackievirus B5 induced apoptosis of HeLa cells: Effects on p53 and SUMO. Virology 396, 256263.
  • 62
    Young, L. S. and Rickinson, A. B. (2004) Epstein-Barr virus: 40 years on. Nat. Rev. Cancer. 4, 757768.
  • 63
    Bentz, G. L., Whitehurst, C. B., and Pagano, J. S. (2011) Epstein-Barr virus latent membrane protein 1 (LMP1) C-terminal-activating region 3 contributes to LMP1-mediated cellular migration via its interaction with Ubc9. J. Virol. 85, 1014410153.
  • 64
    Bentz, G. L., Shackelford, J., and Pagano, J. S. (2012) Epstein-Barr virus latent membrane protein 1 regulates the function of interferon regulatory factor 7 by inducing its sumoylation. J. Virol. 86, 1225112261.
  • 65
    Yousef, A. F., Fonseca, G. J., Pelka, P., Ablack, J. N., Walsh, C., et al. (2010) Identification of a molecular recognition feature in the E1A oncoprotein that binds the SUMO conjugase UBC9 and likely interferes with polySUMOylation. Oncogene 29, 46934704.
  • 66
    Boutell, C. and Everett, R. D. (2013) Regulation of alphaherpesvirus infections by the ICP0 family of proteins. J. Gen. Virol. 94, 465481.
  • 67
    Yueh, A., Leung, J., Bhattacharyya, S., Perrone, L. A., de los Santos, K., et al. (2006) Interaction of moloney murine leukemia virus capsid with Ubc9 and PIASy mediates SUMO-1 addition required early in infection. J. Virol. 80, 342352.
  • 68
    Jaber, T., Bohl, C. R., Lewis, G. L., Wood, C., West, J. T., Jr., et al. (2009) Human Ubc9 contributes to production of fully infectious human immunodeficiency virus type 1 virions. J. Virol. 83, 1044810459.
  • 69
    Bohl, C. R., Abrahamyan, L. G., and Wood, C. (2013) Human Ubc9 is involved in intracellular HIV-1 Env stability after trafficking out of the trans-Golgi network in a Gag dependent manner. PloS One. 8, e69359.
  • 70
    Sinigalia, E., Alvisi, G., Segre, C. V., Mercorelli, B., Muratore, G., et al. (2012) The human cytomegalovirus DNA polymerase processivity factor UL44 is modified by SUMO in a DNA-dependent manner. PloS One. 7, e49630.
  • 71
    Alfadhli, A., Love, Z., Arvidson, B., Seeds, J., Willey, J., et al. (2001) Hantavirus nucleocapsid protein oligomerization. J. Virol. 75, 20192023.
  • 72
    Maeda, A., Lee, B. H., Yoshimatsu, K., Saijo, M., Kurane, I., et al. (2003) The intracellular association of the nucleocapsid protein (NP) of hantaan virus (HTNV) with small ubiquitin-like modifier-1 (SUMO-1) conjugating enzyme 9 (Ubc9). Virology 305, 288297.
  • 73
    Xu, K., Klenk, C., Liu, B., Keiner, B., Cheng, J., et al. (2011) Modification of nonstructural protein 1 of influenza A virus by SUMO1. J. Virol. 85, 10861098.
  • 74
    Wu, Y. C., Roark, A. A., Bian, X. L., and Wilson, V. G. (2008) Modification of papillomavirus E2 proteins by the small ubiquitin-like modifier family members (SUMOs). Virology 378, 329338.
  • 75
    Miller, G., El-Guindy, A., Countryman, J., Ye, J., and Gradoville, L. (2007) Lytic cycle switches of oncogenic human gammaherpesviruses. Adv. Cancer Res. 97, 81109.
  • 76
    Chang, L. K., Lee, Y. H., Cheng, T. S., Hong, Y. R., Lu, P.J., et al. (2004) Post-translational modification of Rta of Epstein-Barr virus by SUMO-1. J. Biol. Chem. 279, 3880338812.
  • 77
    Liu, S. T., Wang, W. H., Hong, Y. R., Chuang, J. Y., Lu, P. J., et al. (2006) Sumoylation of Rta of Epstein-Barr virus is preferentially enhanced by PIASxbeta. Virus Res. 119, 163170.
  • 78
    Chang, L. K., Liu, S. T., Kuo, C. W., Wang, W. H., Chuang, J. Y., et al. (2008) Enhancement of transactivation activity of Rta of Epstein-Barr virus by RanBPM. J. Mol. Biol. 379, 231242.
  • 79
    Ribet, D., Hamon, M., Gouin, E., Nahori, M. A., Impens, F., et al. (2010) Listeria monocytogenes impairs SUMOylation for efficient infection. Nature 464, 11921195.
  • 80
    Moschos, S. J., Jukic, D. M., Athanassiou, C., Bhargava, R., Dacic, S., et al. (2010) Expression analysis of Ubc9, the single small ubiquitin-like modifier (SUMO) E2 conjugating enzyme, in normal and malignant tissues. Hum. Pathol. 41, 12861298.
  • 81
    Mo, Y. Y., Yu, Y., Ee, P. L., and Beck, W. T. (2004) Overexpression of a dominant-negative mutant Ubc9 is associated with increased sensitivity to anticancer drugs. Cancer Res. 64, 27932798.
  • 82
    Boggio, R., Passafaro, A., and Chiocca, S. (2007) Targeting SUMO E1 to ubiquitin ligases: A viral strategy to counteract sumoylation. J. Biol. Chem. 282, 1537615382.
  • 83
    Pozzebon, M. E., Varadaraj, A., Mattoscio, D., Jaffray, E. G., Miccolo, C., et al. (2013) BC-box protein domain-related mechanism for VHL protein degradation. Proc. Natl. Acad. Sci. USA 110, 1816818173.