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Crosstalk Between the SUMO and Ubiquitin Pathways

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Part of the book series: Ernst Schering Foundation Symposium Proceedings ((SCHERING FOUND,volume 2008/1))

Abstract

Several ways in which the SUMO and ubiquitin pathways can intersect and communicate have recently been discovered. This review discusses the principles of crosstalk between SUMOylation and ubiquitination, focusing on the RNF4 family of RING finger E3 ubiquitin ligases, which specifically recognize SUMOylated proteins via their SUMO moiety for ubiquitination.

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References

  • al-Khodairy F, Enoch T, Hagan IM, Carr AM (1995) The Schizosaccharomyces pombe hus5 gene encodes a ubiquitin conjugating enzyme required for normal mitosis. J Cell Sci 108:475–486

    CAS  PubMed  Google Scholar 

  • Andersen PL, Xu F, Xiao W (2008) Eukaryotic DNA damage tolerance and translesion synthesis through covalent modifications of PCNA. Cell Res 18:162–173

    Article  CAS  PubMed  Google Scholar 

  • Andrews EA, Palecek J, Sergeant J, Taylor E, Lehmann AR, Watts FZ (2005) Nse2, a component of the Smc5–6 complex, is a SUMO ligase required for the response to DNA damage. Mol Cell Biol 25:185–196

    Article  CAS  PubMed  Google Scholar 

  • Azam M, Lee JY, Abraham V, Chanoux R, Schoenly KA, Johnson FB (2006) Evidence that the S. cerevisiae Sgs1 protein facilitates recombinational repair of telomeres during senescence. Nucleic Acids Res 34:506–516

    Article  CAS  PubMed  Google Scholar 

  • Bernier-Villamor V, Sampson DA, Matunis MJ, Lima CD (2002) Structural basis for E2-mediated SUMO conjugation revealed by a complex between ubiquitin-conjugating enzyme Ubc9 and RanGAP1. Cell 108:345–356

    Article  CAS  PubMed  Google Scholar 

  • Boddy MN, Shanahan P, McDonald WH, Lopez-Girona A, Noguchi E, Yates JR, Russell P (2003) Replication checkpoint kinase Cds1 regulates recombinational repair protein Rad60. Mol Cell Biol 23:5939–5946

    Article  CAS  PubMed  Google Scholar 

  • Burgess RC, Rahman S, Lisby M, Rothstein R, Zhao X (2007) The Slx5/8 complex affects sumoylation of DNA repair proteins and negatively regulates recombination. Mol Cell Biol 27:6153–6162

    Article  CAS  PubMed  Google Scholar 

  • Bylebyl GR, Belichenko I, Johnson ES (2003) The SUMO isopeptidase Ulp2 prevents accumulation of SUMO chains in yeast. J Biol Chem 278:44113–44120

    Article  CAS  PubMed  Google Scholar 

  • Cavallo F, Astolfi A, Iezzi M, Cordero F, Lollini PL, Forni G, Calogero R (2005) An integrated approach of immunogenomics and bioinformatics to identify new tumor associated antigens (TAA) for mammary cancer immunological prevention. BMC Bioinform 6 [Suppl 4]:S7

    Article  CAS  Google Scholar 

  • Cheng J, Kang X, Zhang S, Yeh ET (2007) SUMO-specific protease 1 is essential for stabilization of HIF1alpha during hypoxia. Cell 131:584–595

    Article  CAS  PubMed  Google Scholar 

  • Darst RP, Garcia SN, Koch MR, Pillus L (2007) Slx5 promotes transcriptional silencing and is required for robust growth in the absence of Sir2. Mol Cell Biol 28:1361–1372

    Article  PubMed  CAS  Google Scholar 

  • Galili N, Nayak S, Epstein JA, Buck CA (2000) Rnf4, a RING protein expressed in the developing nervous and reproductive systems, interacts with Gscl, a gene within the DiGeorge critical region. Dev Dyn 218:102–111

    Article  CAS  PubMed  Google Scholar 

  • Gill G (2004) SUMO and ubiquitin in the nucleus: different functions, similar mechanisms? Genes Dev 18:2046–2059

    Article  CAS  PubMed  Google Scholar 

  • Hakli M, Karvonen U, Janne OA, Palvimo JJ (2005) SUMO-1 promotes association of SNURF (RNF4) with PML nuclear bodies. Exp Cell Res 304:224–233

    Article  PubMed  CAS  Google Scholar 

  • Hannich JT, Lewis A, Kroetz MB, Li SJ, Heide H, Emili A, Hochstrasser M (2005) Defining the SUMO-modified proteome by multiple approaches in Saccharomyces cerevisiae. J Biol Chem 280:4102–4110

    Article  CAS  PubMed  Google Scholar 

  • Hay RT (2005) SUMO: a history of modification. Mol Cell 18:1–12

    Article  CAS  PubMed  Google Scholar 

  • Hazbun TR, Malmstrom L, Anderson S, Graczyk BJ, Fox B, Riffle M, Sundin BA, Aranda JD, McDonald WH, Chiu CH, Snydsman BE, Bradley P, Muller EG, Fields S, Baker D, Yates JR, Davis TN (2003) Assigning function to yeast proteins by integration of technologies. Mol Cell 12:1353–1365

    Article  CAS  PubMed  Google Scholar 

  • Hecker CM, Rabiller M, Haglund K, Bayer P, Dikic I (2006) Specification of SUMO1- and SUMO2-interacting motifs. J Biol Chem 281:16117–16127

    Article  CAS  PubMed  Google Scholar 

  • Hunter T (2007) The age of crosstalk: phosphorylation, ubiquitination and beyond. Mol Cell 28:730–738

    Article  CAS  PubMed  Google Scholar 

  • Ii T, Fung J, Mullen JR, Brill SJ (2007a) The yeast Slx5-Slx8 DNA integrity complex displays ubiquitin ligase activity. Cell Cycle 6:2800–2809

    Article  CAS  PubMed  Google Scholar 

  • Ii T, Mullen JR, Slagle CE, Brill SJ (2007b) Stimulation of in vitro sumoylation by Slx5-Slx8: evidence for a functional interaction with the SUMO pathway. DNA Repair 6:1679–1691

    Article  CAS  PubMed  Google Scholar 

  • Johnson ES (2004) Protein modification by SUMO. Annu Rev Biochem 73:355–382

    Article  CAS  PubMed  Google Scholar 

  • Kaiser FJ, Moroy T, Chang GT, Horsthemke B, Ludecke HJ (2003) The RING finger protein RNF4, a co-regulator of transcription, interacts with the TRPS1 transcription factor. J Biol Chem 278:38780–38785

    Article  CAS  PubMed  Google Scholar 

  • Kosoy A, Calonge TM, Outwin EA, O'Connell MJ (2007) Fission yeast Rnf4 homologs are required for DNA repair. J Biol Chem 282:20388–20394

    Article  CAS  PubMed  Google Scholar 

  • Lallemand-Breitenbach V, Jeanne M, Benhanda S, Nasr R, Lei M, Peres L, Zhou J, Zhu J, Raught B, de The H (2008) Arsenic degrades PML or PML-RARa through a SUMO-triggered RNF4/ubiquitin-mediated pathway. Nat Cell Biol 10:547–555

    Article  CAS  PubMed  Google Scholar 

  • Linke K, Mace PD, Smith CA, Vaux DL, Silke J, Day CL (2008) Structure of the MDM 2/MDMX RING domain heterodimer reveals dimerization is required for their ubiquitylation in trans. Cell Death Differ 15:841–848

    Article  CAS  PubMed  Google Scholar 

  • Lyngso C, Bouteiller G, Damgaard CK, Ryom D, Sanchez-Munoz S, Norby PL, Bonven BJ, Jorgensen P (2000) Interaction between the transcription factor SPBP and the positive cofactor RNF4. An interplay between protein binding zinc fingers. J Biol Chem 275:26144–26149

    Article  CAS  PubMed  Google Scholar 

  • McDonald WH, Pavlova Y, Yates JR, Boddy MN (2003) Novel essential DNA repair proteins Nse1 and Nse2 are subunits of the fission yeast Smc5-Smc6 complex. J Biol Chem 278:45460–45467

    Article  CAS  PubMed  Google Scholar 

  • Meulmeester E, Kunze M, Hsiao HH, Urlaub H, Melchior F (2008) Mechanism and consequences for paralog-specific sumoylation of ubiquitin-specific protease 25. Mol Cell 30:610–619

    Article  CAS  PubMed  Google Scholar 

  • Minty A, Dumont X, Kaghad M, 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. 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

    Article  CAS  PubMed  Google Scholar 

  • Moilanen AM, Poukka H, Karvonen U, Hakli M, Janne OA, Palvimo JJ (1998) Identification of a novel RING finger protein as a coregulator in steroid receptor-mediated gene transcription. Mol Cell Biol 18:5128–5139

    CAS  PubMed  Google Scholar 

  • Mullen JR, Kaliraman V, Ibrahim SS, Brill SJ (2001) Requirement for three novel protein complexes in the absence of the Sgs1 DNA helicase in Saccharomyces cerevisiae. Genetics 157:103–118

    CAS  PubMed  Google Scholar 

  • Perry JJ, Tainer JA, Boddy MN (2008) A SIM-ultaneous role for SUMO and ubiquitin. Trends Cell Biol 33:201–208

    CAS  Google Scholar 

  • Pichler A, Knipscheer P, Oberhofer E, van Dijk WJ, Korner R, Olsen JV, Jentsch S, Melchior F, Sixma TK (2005) SUMO modification of the ubiquitin-conjugating enzyme E2-25K. Nat Struct Mol Biol 12:264–269

    Article  CAS  PubMed  Google Scholar 

  • Poyurovsky MV, Priest C, Kentsis A, Borden KL, Pan ZQ, Pavletich N, Prives C (2007) The Mdm2 RING domain C-terminus is required for supramolecular assembly and ubiquitin ligase activity. EMBO J 26:90–101

    Article  CAS  PubMed  Google Scholar 

  • Prudden J, Pebernard S, Raffa G, Slavin DA, Perry JJ, Tainer JA, McGowan CH, Boddy MN (2007) SUMO-targeted ubiquitin ligases in genome stability. EMBO J 26:4089–4101

    Article  CAS  PubMed  Google Scholar 

  • Raffa GD, Wohlschlegel J, Yates JR, Boddy MN (2006) SUMO-binding motifs mediate the RAD60-dependent response to replicative stress and self association. J Biol Chem 281:27973–27981

    Article  CAS  PubMed  Google Scholar 

  • Reverter D, Lima CD (2005) Insights into E3 ligase activity revealed by a SUMO-RanGAP1-Ubc9-Nup358 complex. Nature 435:687–692

    Article  CAS  PubMed  Google Scholar 

  • Shayeghi M, Doe CL, Tavassoli M, Watts FZ (1997) Characterisation of Schizosaccharomyces pombe rad31, a UBA-related gene required for DNA damage tolerance. Nucleic Acids Res 25:1162–1169

    Article  CAS  PubMed  Google Scholar 

  • Sobko A, Ma H, Firtel RA (2002) Regulated SUMOylation and ubiquitination of DdMEK1 is required for proper chemotaxis. Dev Cell 2:745–756

    Article  CAS  PubMed  Google Scholar 

  • Song J, Durrin LK, Wilkinson TA, Krontiris TG, Chen Y (2004) Identification of a SUMO-binding motif that recognizes SUMO-modified proteins. Proc Natl Acad Sci U S A 101:14373–11438

    Article  CAS  PubMed  Google Scholar 

  • Song J, Zhang Z, Hu W, Chen Y (2005) Small ubiquitin-like modifier (SUMO) recognition of a SUMO binding motif: a reversal of the bound orientation. J Biol Chem 280:40122–40129

    Article  CAS  PubMed  Google Scholar 

  • Sun H, Leverson JD, Hunter T (2007) Conserved function of RNF4 family proteins in eukaryotes: targeting a ubiquitin ligase to SUMOylated proteins. EMBO J 26:4102–4112

    Article  CAS  PubMed  Google Scholar 

  • Tanaka K, Nishide J, Okazaki K, Kato H, Niwa O, Nakagawa T, Matsuda H, Kawamukai M, Murakami Y (1999) 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 19:8660–8672

    CAS  PubMed  Google Scholar 

  • Tatham MH, Jaffray E, Vaughan OA, Desterro JM, Botting CH, Naismith JH, Hay RT (2001) Polymeric chains of SUMO-2 and SUMO-3 are conjugated to protein substrates by SAE1/SAE2 and Ubc9. J Biol Chem 276:35368–35374

    Article  CAS  PubMed  Google Scholar 

  • Tatham MH, Geoffroy M-C, Shen L, Plechanovova A, Hattersely N, Jaffray EG, Palvimo JJ, Hay RT (2008) RNF4 is a poly-SUMO-specific E3 ubiquitin ligase required for arsenic-induced PML degradation. Nat Cell Biol 10:538–546

    Article  CAS  PubMed  Google Scholar 

  • Torres-Rosell J, Sunjevaric I, De Piccoli G, Sacher M, Eckert-Boulet N, Reid R, Jentsch S, Rothstein R, Aragon L, Lisby M (2007) The Smc5-Smc6 complex and SUMO modification of Rad52 regulates recombinational repair at the ribosomal gene locus. Nat Cell Biol 9:923–931

    Article  CAS  PubMed  Google Scholar 

  • Uetz P, Giot L, Cagney G, Mansfield TA, Judson RS, Knight JR, Lockshon D, Narayan V, Srinivasan M, Pochart P, Qureshi-Emili A, Li Y, Godwin B, Conover D, Kalbfleisch T, Vijayadamodar G, Yang M, Johnston M, Fields S, Rothberg JM (2000) A comprehensive analysis of protein–protein interactions in Saccharomyces cerevisiae. Nature 403:623–627

    Article  CAS  PubMed  Google Scholar 

  • Uldrijan S, Pannekoek WJ, Vousden KH (2007) An essential function of the extreme C-terminus of MDM 2 can be provided by MDMX. EMBO J 26:102–112

    Article  CAS  PubMed  Google Scholar 

  • Uzunova K, Gottsche K, Miteva M, Weisshaar SR, Glanemann C, Schnellhardt M, Niessen M, Scheel H, Hofmann K, Johnson ES, Praefcke GJ, Dohmen RJ (2007) Ubiquitin-dependent proteolytic control of SUMO conjugates. J Biol Chem 282:34167–34175

    Article  CAS  PubMed  Google Scholar 

  • Wang Z, Jones GM, Prelich G (2006) Genetic analysis connects SLX5 and SLX8 to the SUMO pathway in Saccharomyces cerevisiae. Genetics 172:1499–1509

    Article  CAS  PubMed  Google Scholar 

  • Wu SM, Kuo WC, Hwu WL, Hwa KY, Mantovani R, Lee YM (2004) RNF4 is a coactivator for nuclear factor Y on GTP cyclohydrolase I proximal promoter. Mol Pharmacol 66:1317–1324

    Article  CAS  PubMed  Google Scholar 

  • Xhemalce B, Seeler JS, Thon G, Dejean A, Arcangioli B (2004) Role of the fission yeast SUMO E3 ligase Pli1p in centromere and telomere maintenance. EMBO J 23:3844–3853

    Article  CAS  PubMed  Google Scholar 

  • Xie Y, Kerscher O, Kroetz MB, McConchie HF, Sung P, Hochstrasser M (2007) The yeast HEX3-SLX8 heterodimer is a ubiquitin ligase stimulated by substrate sumoylation. J Biol Chem 282:34176–34184

    Article  CAS  PubMed  Google Scholar 

  • Zhang C, Roberts TM, Yang J, Desai R, Brown GW (2006) Suppression of genomic instability by SLX5 and SLX8 in Saccharomyces cerevisiae. DNA Repair 5:336–346

    Article  CAS  PubMed  Google Scholar 

  • Zhao X, Blobel G (2005) A SUMO ligase is part of a nuclear multiprotein complex that affects DNA repair and chromosomal organization. Proc Natl Acad Sci U S A 102:4777–4782

    Article  CAS  PubMed  Google Scholar 

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Correspondence to T. Hunter .

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S. Jentsch B. Haendler

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© 2008 Springer-Verlag

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Hunter, T., Sun, H. (2008). Crosstalk Between the SUMO and Ubiquitin Pathways. In: Jentsch, S., Haendler, B. (eds) The Ubiquitin System in Health and Disease. Ernst Schering Foundation Symposium Proceedings, vol 2008/1. Springer, Berlin, Heidelberg. https://doi.org/10.1007/2789_2008_098

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  • DOI: https://doi.org/10.1007/2789_2008_098

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  • Print ISBN: 978-3-540-85106-6

  • Online ISBN: 978-3-540-85107-3

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