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.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsReferences
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
Andersen PL, Xu F, Xiao W (2008) Eukaryotic DNA damage tolerance and translesion synthesis through covalent modifications of PCNA. Cell Res 18:162–173
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
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
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
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
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
Bylebyl GR, Belichenko I, Johnson ES (2003) The SUMO isopeptidase Ulp2 prevents accumulation of SUMO chains in yeast. J Biol Chem 278:44113–44120
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
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
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
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
Gill G (2004) SUMO and ubiquitin in the nucleus: different functions, similar mechanisms? Genes Dev 18:2046–2059
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
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
Hay RT (2005) SUMO: a history of modification. Mol Cell 18:1–12
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
Hecker CM, Rabiller M, Haglund K, Bayer P, Dikic I (2006) Specification of SUMO1- and SUMO2-interacting motifs. J Biol Chem 281:16117–16127
Hunter T (2007) The age of crosstalk: phosphorylation, ubiquitination and beyond. Mol Cell 28:730–738
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
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
Johnson ES (2004) Protein modification by SUMO. Annu Rev Biochem 73:355–382
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
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
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
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
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
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
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
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
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
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
Perry JJ, Tainer JA, Boddy MN (2008) A SIM-ultaneous role for SUMO and ubiquitin. Trends Cell Biol 33:201–208
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
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
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
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
Reverter D, Lima CD (2005) Insights into E3 ligase activity revealed by a SUMO-RanGAP1-Ubc9-Nup358 complex. Nature 435:687–692
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
Sobko A, Ma H, Firtel RA (2002) Regulated SUMOylation and ubiquitination of DdMEK1 is required for proper chemotaxis. Dev Cell 2:745–756
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
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
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
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
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
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
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
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
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
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
Wang Z, Jones GM, Prelich G (2006) Genetic analysis connects SLX5 and SLX8 to the SUMO pathway in Saccharomyces cerevisiae. Genetics 172:1499–1509
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
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
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
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
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
Author information
Authors and Affiliations
Corresponding author
Editor information
Rights and permissions
Copyright information
© 2008 Springer-Verlag
About this paper
Cite this paper
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
Download citation
DOI: https://doi.org/10.1007/2789_2008_098
Published:
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-540-85106-6
Online ISBN: 978-3-540-85107-3
eBook Packages: MedicineMedicine (R0)