SUMO is a small ubiquitin-related modifier implicated in control of various cellular processes including gene transcription, cell cycle, DNA repair and apoptosis. Here we describe details of the SUMO molecular machineries implicated in the formation of signaling networks that underlie the specificity in these biological processes. SUMO signaling is also altered during development of human diseases, including cancer pathogenesis, and these alterations can be explored as a possible drug target.
Keywords: SUMO, Ubiquitin, NFκB, PCNA, RanGAP1, RanBP2, nucleocytoplasmic transport, reptin, KAI1, PTP1B, cancer pathogenesis
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Alkuraya, F.S., Saadi, I., Lund, J.J., Turbe-Doan, A., Morton, C.C., and Maas, R.L. (2006) SUMO1 haploinsufficiency leads to cleft lip and palate. Science 313: 1751.
Ayaydin, F., and Dasso, M. (2004) Distinct in vivo dynamics of vertebrate SUMO paralogues. Mol. Biol. Cell 15: 5208-5218.
Baek, S.H. (2006) A novel link between SUMO modification and cancer metastasis. Cell Cycle 5: 1492-1495.
Bauer, A., Chauvet, S., Huber, O., Usseglio, F., Rothbacher, U., Aragnol, D., Kemler, R., and Pradel, J. (2000) Pontin52 and reptin52 function as antagonistic regulators of beta-catenin signalling activity. EMBO J. 19: 6121-6130.
Dadke, S., Cotteret, S., Yip, S.C., Jaffer, Z.M., Haj, F., Ivanov, A., Rauscher, F., 3rd, Shuai, K., Ng, T., Neel, B.G., and Chernoff, J. (2007) Regulation of protein tyrosine phosphatase 1B by sumoylation. Nat. Cell Biol. 9: 80-85.
Desterro, J.M., Rodriguez, M.S., and Hay, R.T. (1998) SUMO-1 modification of IkappaBalpha inhibits NF-kappaB activation. Mol. Cell 2: 233-239.
Gill, G. (2003) Post-translational modification by the small ubiquitin-related modifier SUMO has big effects on transcription factor activity. Curr. Opin. Genet. Dev. 13: 108-113.
Gill, G. (2005) Something about SUMO inhibits transcription. Curr. Opin. Genet. Dev. 15: 536-541.
Gutierrez, G.J., and Ronai, Z. (2006) Ubiquitin and SUMO systems in the regulation of mitotic checkpoints. Trends Biochem. Sci. 31: 324-332.
Haglund, K., and Dikic, I. (2005) Ubiquitylation and cell signaling. EMBO J. 24: 1-7.
Hay, R.T. (2005) SUMO: a history of modification. Mol. Cell 18: 1-12.
Hecker, C.M., Rabiller, M., Haglund, K., Bayer, P., and Dikic, I. (2006) Specification of SUMO1- and SUMO2-interacting motifs. J. Biol. Chem. 281: 16117-16127.
Hershko, A., and Ciechanover, A. (1998) The ubiquitin system. Annu. Rev. Biochem. 67: 425-479.
Hicke, L., Schubert, H.L., and Hill, C.P. (2005) Ubiquitin-binding domains. Nat. Rev. Mol. Cell Biol. 6: 610-621.
Hoege, C., Pfander, B., Moldovan, G.L., Pyrowolakis, G., and Jentsch, S. (2002) RAD6-dependent DNA repair is linked to modification of PCNA by ubiquitin and SUMO. Nature 419: 135-141.
Hoeller, D., Hecker, C.M., and Dikic, I. (2006) Ubiquitin and ubiquitin-like proteins in cancer pathogenesis. Nat. Rev. Cancer 6: 776-788.
Hooker, G.W., and Roeder, G.S. (2006) A Role for SUMO in meiotic chromosome synapsis. Curr. Biol. 16: 1238-1243.
Huang, T.T., Wuerzberger-Davis, S.M., Wu, Z.H., and Miyamoto, S. (2003) Sequential modification of NEMO/IKKgamma by SUMO-1 and ubiquitin mediates NF-kappaB activation by genotoxic stress. Cell 115: 565-576.
Johnson, E.S., and Blobel, G. (1997). Ubc9p is the conjugating enzyme for the ubiquitin-like protein Smt3p. J. Biol. Chem. 272: 26799-26802.
Kamitani, T., Nguyen, H.P., Kito, K., Fukuda-Kamitani, T., and Yeh, E.T. (1998) Covalent modification of PML by the sentrin family of ubiquitin-like proteins. J. Biol. Chem. 273: 3117-3120.
Kim, J.H., Choi, H.J., Kim, B., Kim, M.H., Lee, J.M., Kim, I.S., Lee, M.H., Choi, S.J., Kim, K.I., Kim, S.I., et al. (2006) Roles of sumoylation of a reptin chromatin-remodelling complex in cancer metastasis. Nat. Cell. Biol. 8: 631-639.
Lyst, M.J., Nan, X., and Stancheva, I. (2006) Regulation of MBD1-mediated transcriptional repression by SUMO and PIAS proteins. EMBO J. 25: 5317-5328.
Mahajan, R., Delphin, C., Guan, T., Gerace, L., and Melchior, F. (1997) A small ubiquitinrelated polypeptide involved in targeting RanGAP1 to nuclear pore complex protein RanBP2. Cell 88: 97-107.
Mahajan, R., Gerace, L., and Melchior, F. (1998) Molecular characterization of the SUMO-1 modification of RanGAP1 and its role in nuclear envelope association. J. Cell Biol. 140: 259-270.
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. 13: 1457-1470.
Matunis, M.J., Wu, J., and Blobel, G. (1998) SUMO-1 modification and its role in targeting the Ran GTPase-activating protein, RanGAP1, to the nuclear pore complex. J. Cell Biol. 140: 499-509.
Melchior, F. (2000). SUMO-nonclassical ubiquitin. Annu. Rev. Cell Dev. Biol. 16: 591-626.
Minty, A., Dumont, X., Kaghad, M., and Caput, D. (2000) 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. 275: 36316-36323.
Mo, Y.Y., and Moschos, S.J. (2005) Targeting Ubc9 for cancer therapy. Expert Opin. Ther. Targets 9: 1203-1216.
Moon, R.T., Kohn, A.D., De Ferrari, G.V., and Kaykas, A. (2004) WNT and beta-catenin signalling: diseases and therapies. Nat. Rev. Genet. 5: 691-701.
Muller, S., Ledl, A., and Schmidt, D. (2004) SUMO: a regulator of gene expression and genome integrity. Oncogene 23: 1998-2008.
Nacerddine, K., Lehembre, F., Bhaumik, M., Artus, J., Cohen-Tannoudji, M., Babinet, C., Pandolfi, P.P., and Dejean, A. (2005) The SUMO pathway is essential for nuclear integrity and chromosome segregation in mice. Dev. Cell 9: 769-779.
Papouli, E., Chen, S., Davies, A.A., Huttner, D., Krejci, L., Sung, P., and Ulrich, H.D. (2005) Crosstalk between SUMO and ubiquitin on PCNA is mediated by recruitment of the helicase Srs2p. Mol. Cell 19: 123-133.
Pascual, G., Fong, A.L., Ogawa, S., Gamliel, A., Li, A.C., Perissi, V., Rose, D.W., Willson, T.M., Rosenfeld, M.G., and Glass, C.K. (2005). A SUMOylation-dependent pathway mediates transrepression of inflammatory response genes by PPAR-gamma. Nature 437: 759-763.
Pfander, B., Moldovan, G.L., Sacher, M., Hoege, C., and Jentsch, S. (2005a) SUMO-modified PCNA recruits Srs2 to prevent recombination during S phase. Nature 436: 428-433.
Pfander, B., Moldovan, G.L., Sacher, M., Hoege, C., and Jentsch, S. (2005b) SUMO-modified PCNA recruits Srs2 to prevent recombination during S phase. Nature 136: 428-433.
Pichler, A., Knipscheer, P., Oberhofer, E., van Dijk, W.J., Korner, R., Olsen, J.V., Jentsch, S., Melchior, F., and Sixma, T.K. (2005) SUMO modification of the ubiquitin-conjugating enzyme E2-25K. Nat. Struct. Mol. Biol. 12: 264-269.
Rajendra, R., Malegaonkar, D., Pungaliya, P., Marshall, H., Rasheed, Z., Brownell, J., Liu, L.F., Lutzker, S., Saleem, A., and Rubin, E.H. (2004) Topors functions as an E3 ubiquitin ligase with specific E2 enzymes and ubiquitinates p53. J. Biol. Chem. 279: 36440-36444.
Reya, T., and Clevers, H. (2005) Wnt signalling in stem cells and cancer. Nature 434: 843-850.
Rosas-Acosta, G., Russell, W.K., Deyrieux, A., Russell, D.H., and Wilson, V.G. (2005) A universal strategy for proteomic studies of SUMO and other ubiquitin-like modifiers. Mol. Cell Proteomics 4: 56-72.
Saitoh, H., and Hinchey, J. (2000). Functional heterogeneity of small ubiquitin-related protein modifiers SUMO-1 versus SUMO-2/3. J. Biol. Chem. 275: 6252-6258.
Seeler, J.S., and Dejean, A. (2003) Nuclear and unclear functions of SUMO. Nat. Rev. Mol. Cell Biol. 4: 690-699.
Seet, B.T., Dikic, I., Zhou, M.M., and Pawson, T. (2006) Reading protein modifications with interaction domains. Nat. Rev. Mol. Cell Biol. 7: 473-483.
Shen, T.H., Lin, H.K., Scaglioni, P.P., Yung, T.M., and Pandolfi, P.P. (2006) The mechanisms of PML-nuclear body formation. Mol. Cell 24: 331-339.
Song, J., Durrin, L.K., Wilkinson, T.A., Krontiris, T.G., and Chen, Y. (2004) Identification of a SUMO-binding motif that recognizes SUMO-modified proteins. Proc. Natl. Acad. Sci. USA 101: 14373-14378.
Uchimura, Y., Ichimura, T., Uwada, J., Tachibana, T., Sugahara, S., Nakao, M., and Saitoh, H. (2006) Involvement of SUMO modification in MBD1- and MCAF1-mediated heterochromatin formation. J. Biol. Chem. 281: 23180-23190.
Ulrich, H.D. (2005a) Mutual interactions between the SUMO and ubiquitin systems: a plea of no contest. Trends Cell Biol. 15: 525-532.
Ulrich, H.D. (2005b) SUMO modification: wrestling with protein conformation. Curr. Biol. 15: R257-259.
Ulrich, H.D., Vogel, S., and Davies, A.A. (2005) SUMO keeps a check on recombination during DNA replication. Cell Cycle 4: 1699-1702.
Vertegaal, A.C., Ogg, S.C., Jaffray, E., Rodriguez, M.S., Hay, R.T., Andersen, J.S., Mann, M., and Lamond, A.I. (2004). A proteomic study of SUMO-2 target proteins. J. Biol. Chem. 279: 33791-33798.
Weger, S., Hammer, E., and Heilbronn, R. (2005) Topors acts as a SUMO-1 E3 ligase for p53 in vitro and in vivo. FEBS Lett. 579: 5007-5012.
Weissman, A.M. (2001) Themes and variations on ubiquitylation. Nat. Rev. Mol. Cell Biol. 2: 169-178.
Willert, K., and Jones, K.A. (2006) Wnt signaling: is the party in the nucleus? Genes Dev. 20: 1394-1404.
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Hecker, CM., Dikic, I. (2007). Protein Complexes in SUMO Signaling. In: Pifat-Mrzljak, G. (eds) Supramolecular Structure and Function 9. Springer, Dordrecht. https://doi.org/10.1007/978-1-4020-6466-1_5
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