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Regulation of Cellular Processes by SUMO: Understudied Topics

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SUMO Regulation of Cellular Processes

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 963))

Abstract

SUMO plays a multiple role in maintenance of cellular homeostasis, both under normal conditions and under cell stress . Considerable effort has been devoted to unraveling the functions of SUMO in regulation of transcription and preservation of genome stability. However, it is clear from high-throughput SUMO proteome studies that SUMO likely regulates many more cellular processes. The function of SUMO in these processes has hardly been explored. This review will focus on the emerging function of SUMO in regulation of several of these processes.

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References

  • Albuquerque CP, Wang G, Lee NS, Kolodner RD, Putnam CD, Zhou H (2013) Distinct SUMO ligases cooperate with Esc2 and Slx5 to suppress duplication-mediated genome rearrangements. PLoS Genet 9:e1003670

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Arito M, Horiba T, Hachimura S, Inoue J, Sato R (2008) Growth factor-induced phosphorylation of sterol regulatory element-binding proteins inhibits sumoylation, thereby stimulating the expression of their target genes, low density lipoprotein uptake, and lipid synthesis. J Biol Chem 283:15224–15231

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Athanasiadis A, Rich A, Maas S (2004) Widespread A-to-I RNA editing of Alu-containing mRNAs in the human transcriptome. PLoS Biol 2:e391

    Article  PubMed  PubMed Central  Google Scholar 

  • Bellail AC, Olson JJ, Hao C (2014) SUMO1 modification stabilizes CDK6 protein and drives the cell cycle and glioblastoma progression. Nat Commun 5:4234

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bergink S, Jentsch S (2009) Principles of ubiquitin and SUMO modifications in DNA repair. Nature 458:461–467

    Article  CAS  PubMed  Google Scholar 

  • Bisht KS, Bradbury CM, Mattson D, Kaushal A, Sowers A, Markovina S, Ortiz KL, Sieck LK, Isaacs JS, Brechbiel MW, Mitchell JB, Neckers LM, Gius D (2003) Geldanamycin and 17-allylamino-17-demethoxygeldanamycin potentiate the in vitro and in vivo radiation response of cervical tumor cells via the heat shock protein 90-mediated intracellular signaling and cytotoxicity. Cancer Res 63:8984–8995

    CAS  PubMed  Google Scholar 

  • Bridges AA, Gladfelter AS (2015) Septin form and function at the cell cortex. J Biol Chem 290:17173–17180

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bruderer R, Tatham MH, Plechanovova A, Matic I, Garg AK, Hay RT (2011) Purification and identification of endogenous polySUMO conjugates. EMBO Rep 12:142–148

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Castillo-Lluva S, Tatham MH, Jones RC, Jaffray EG, Edmondson RD, Hay RT, Malliri A (2010) SUMOylation of the GTPase Rac1 is required for optimal cell migration. Nat Cell Biol 12:1078–U1070

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cho SJ, Yun SM, Jo C, Lee DH, Choi KJ, Song JC, Park SI, Kim YJ, Koh YH (2015) SUMO1 promotes Abeta production via the modulation of autophagy. Autophagy 11:100–112

    Article  PubMed  Google Scholar 

  • Chymkowitch P, Nguea AP, Aanes H, Koehler CJ, Thiede B, Lorenz S, Meza-Zepeda LA, Klungland A, Enserink JM (2015a) Sumoylation of Rap1 mediates the recruitment of TFIID to promote transcription of ribosomal protein genes. Genome Res 25:897–906

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chymkowitch P, Nguea PA, Enserink JM (2015b) SUMO-regulated transcription: challenging the dogma. Bioessays 37:1095–1105

    Article  CAS  PubMed  Google Scholar 

  • Dawlaty MM, Malureanu L, Jeganathan KB, Kao E, Sustmann C, Tahk S, Shuai K, Grosschedl R, van Deursen JM (2008) Resolution of sister centromeres requires RanBP2-mediated SUMOylation of topoisomerase II alpha. Cell 133:103–115

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Denison C, Rudner AD, Gerber SA, Bakalarski CE, Moazed D, Gygi SP (2005) A proteomic strategy for gaining insights into protein sumoylation in yeast. Mol Cell Proteomics 4:246–254

    Article  CAS  PubMed  Google Scholar 

  • Dotiwala F, Haase J, Arbel-Eden A, Bloom K, Haber JE (2007) The yeast DNA damage checkpoint proteins control a cytoplasmic response to DNA damage. Proc Natl Acad Sci U S A 104:11358–11363

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Efeyan A, Comb WC, Sabatini DM (2015) Nutrient-sensing mechanisms and pathways. Nature 517:302–310

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Eifler K, Vertegaal AC (2015) SUMOylation-mediated regulation of cell cycle progression and cancer. Trends Biochem Sci 40:779–793

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Enserink JM (2015) Sumo and the cellular stress response. Cell Div 10:4

    Article  PubMed  PubMed Central  Google Scholar 

  • Enserink JM, Smolka MB, Zhou H, Kolodner RD (2006) Checkpoint proteins control morphogenetic events during DNA replication stress in Saccharomyces cerevisiae. J Cell Biol 175:729–741

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Felberbaum R, Wilson NR, Cheng DM, Peng JM, Hochstrasser M (2012) Desumoylation of the endoplasmic reticulum membrane VAP family protein Scs2 by Ulp1 and SUMO regulation of the inositol synthesis pathway. Mol Cell Biol 32:64–75

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Feng Y, Yao Z, Klionsky DJ (2015) How to control self-digestion: transcriptional, post-transcriptional, and post-translational regulation of autophagy. Trends Cell Biol 25:354–363

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Finkbeiner E, Haindl M, Muller S (2011) The SUMO system controls nucleolar partitioning of a novel mammalian ribosome biogenesis complex. EMBO J 30:1067–1078

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Galluzzi L, Pietrocola F, Bravo-San Pedro JM, Amaravadi RK, Baehrecke EH, Cecconi F, Codogno P, Debnath J, Gewirtz DA, Karantza V, Kimmelman A, Kumar S, Levine B, Maiuri MC, Martin SJ, Penninger J, Piacentini M, Rubinsztein DC, Simon HU, Simonsen A, Thorburn AM, Velasco G, Ryan KM, Kroemer G (2015) Autophagy in malignant transformation and cancer progression. EMBO J 34:856–880

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Garcia-Rodriguez N, Wong RP, Ulrich HD (2016) Functions of ubiquitin and SUMO in DNA replication and replication stress. Front Genet 7:87

    Article  PubMed  PubMed Central  Google Scholar 

  • Goldstein JL, DeBose-Boyd RA, Brown MS (2006) Protein sensors for membrane sterols. Cell 124:35–46

    Article  CAS  PubMed  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 

  • Hirano Y, Murata S, Tanaka K, Shimizu M, Sato R (2003) Sterol regulatory element-binding proteins are negatively regulated through SUMO-1 modification independent of the ubiquitin/26 S proteasome pathway. J Biol Chem 278:16809–16819

    Article  CAS  PubMed  Google Scholar 

  • Howell AS, Lew DJ (2012) Morphogenesis and the cell cycle. Genetics 190:51–77

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jackson SP, Durocher D (2013) Regulation of DNA damage responses by ubiquitin and SUMO. Mol Cell 49:795–807

    Article  CAS  PubMed  Google Scholar 

  • Johnson ES, Blobel G (1999) Cell cycle-regulated attachment of the ubiquitin-related protein SUMO to the yeast septins. J Cell Biol 147:981–993

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jongjitwimol J, Feng M, Zhou L, Wilkinson O, Small L, Baldock R, Taylor DL, Smith D, Bowler LD, Morley SJ, Watts FZ (2014) The S. pombe translation initiation factor eIF4G is sumoylated and associates with the SUMO protease Ulp2. PLoS One 9:e94182

    Article  PubMed  PubMed Central  Google Scholar 

  • Kaur J, Debnath J (2015) Autophagy at the crossroads of catabolism and anabolism. Nat Rev Mol Cell Biol 16:461–472

    Article  CAS  PubMed  Google Scholar 

  • Kuma A, Hatano M, Matsui M, Yamamoto A, Nakaya H, Yoshimori T, Ohsumi Y, Tokuhisa T, Mizushima N (2004) The role of autophagy during the early neonatal starvation period. Nature 432:1032–1036

    Article  CAS  PubMed  Google Scholar 

  • Lee GY, Jang H, Lee JH, Huh JY, Choi S, Chung J, Kim JB (2014) PIASy-mediated sumoylation of SREBP1c regulates hepatic lipid metabolism upon fasting signaling. Mol Cell Biol 34:926–938

    Article  PubMed  PubMed Central  Google Scholar 

  • Lisby M, Barlow JH, Burgess RC, Rothstein R (2004) Choreography of the DNA damage response: spatiotemporal relationships among checkpoint and repair proteins. Cell 118:699–713

    Article  CAS  PubMed  Google Scholar 

  • Liu HW, Zhang J, Heine GF, Arora M, Gulcin Ozer H, Onti-Srinivasan R, Huang K, Parvin JD (2012) Chromatin modification by SUMO-1 stimulates the promoters of translation machinery genes. Nucleic Acids Res 40:10172–10186

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liu HW, Banerjee T, Guan X, Freitas MA, Parvin JD (2015) The chromatin scaffold protein SAFB1 localizes SUMO-1 to the promoters of ribosomal protein genes to facilitate transcription initiation and splicing. Nucleic Acids Res 43:3605–3613

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lopes M, Cotta-Ramusino C, Pellicioli A, Liberi G, Plevani P, Muzi-Falconi M, Newlon CS, Foiani M (2001) The DNA replication checkpoint response stabilizes stalled replication forks. Nature 412:557–561

    Article  CAS  PubMed  Google Scholar 

  • Matafora V, D’Amato A, Mori S, Blasi F, Bachi A (2009) Proteomics analysis of nucleolar SUMO-1 target proteins upon proteasome inhibition. Mol Cell Proteomics 8:2243–2255

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Menzies FM, Fleming A, Rubinsztein DC (2015) Compromised autophagy and neurodegenerative diseases. Nat Rev Neurosci 16:345–357

    Article  CAS  PubMed  Google Scholar 

  • Mikkonen L, Hirvonen J, Janne OA (2013) SUMO-1 regulates body weight and adipogenesis via PPARgamma in male and female mice. Endocrinology 154:698–708

    Article  CAS  PubMed  Google Scholar 

  • Mizushima N, Levine B, Cuervo AM, Klionsky DJ (2008) Autophagy fights disease through cellular self-digestion. Nature 451:1069–1075

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mollapour M, Bourboulia D, Beebe K, Woodford MR, Polier S, Hoang A, Chelluri R, Li Y, Guo A, Lee MJ, Fotooh-Abadi E, Khan S, Prince T, Miyajima N, Yoshida S, Tsutsumi S, Xu W, Panaretou B, Stetler-Stevenson WG, Bratslavsky G, Trepel JB, Prodromou C, Neckers L (2014) Asymmetric Hsp90 N domain SUMOylation recruits Aha1 and ATP-competitive inhibitors. Mol Cell 53:317–329

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Naidu SR, Lakhter AJ, Androphy EJ (2012) PIASy-mediated Tip60 sumoylation regulates p53-induced autophagy. Cell Cycle 11:2717–2728

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nakatogawa H, Suzuki K, Kamada Y, Ohsumi Y (2009) Dynamics and diversity in autophagy mechanisms: lessons from yeast. Nat Rev Mol Cell Biol 10:458–467

    Article  CAS  PubMed  Google Scholar 

  • Nishikura K (2016) A-to-I editing of coding and non-coding RNAs by ADARs. Nat Rev Mol Cell Biol 17:83–96

    Article  CAS  PubMed  Google Scholar 

  • Ohshima T, Koga H, Shimotohno K (2004) Transcriptional activity of peroxisome proliferator-activated receptor gamma is modulated by SUMO-1 modification. J Biol Chem 279:29551–29557

    Article  CAS  PubMed  Google Scholar 

  • Panse VG, Hardeland U, Werner T, Kuster B, Hurt E (2004) A proteome-wide approach identifies sumoylated substrate proteins in yeast. J Biol Chem 279:41346–41351

    Article  CAS  PubMed  Google Scholar 

  • Psakhye I, Jentsch S (2012) Protein group modification and synergy in the SUMO pathway as exemplified in DNA repair. Cell 151:807–820

    Article  CAS  PubMed  Google Scholar 

  • Rodriguez-Boulan E, Macara IG (2014) Organization and execution of the epithelial polarity programme. Nat Rev Mol Cell Biol 15:225–242

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Santocanale C, Diffley JF (1998) A Mec1- and Rad53-dependent checkpoint controls late-firing origins of DNA replication. Nature 395:615–618

    Article  CAS  PubMed  Google Scholar 

  • Simonsen A, Tooze SA (2009) Coordination of membrane events during autophagy by multiple class III PI3-kinase complexes. J Cell Biol 186:773–782

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Stepanov GA, Filippova JA, Komissarov AB, Kuligina EV, Richter VA, Semenov DV (2015) Regulatory role of small nucleolar RNAs in human diseases. Biomed Res Int 2015:206849

    Article  PubMed  PubMed Central  Google Scholar 

  • Sung MK, Lim G, Yi DG, Chang YJ, Yang EB, Lee K, Huh WK (2013) Genome-wide bimolecular fluorescence complementation analysis of SUMO interactome in yeast. Genome Res 23:736–746

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sykes SM, Mellert HS, Holbert MA, Li K, Marmorstein R, Lane WS, McMahon SB (2006) Acetylation of the p53 DNA-binding domain regulates apoptosis induction. Mol Cell 24:841–851

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tang Y, Luo J, Zhang W, Gu W (2006) Tip60-dependent acetylation of p53 modulates the decision between cell-cycle arrest and apoptosis. Mol Cell 24:827–839

    Article  CAS  PubMed  Google Scholar 

  • Trepel J, Mollapour M, Giaccone G, Neckers L (2010) Targeting the dynamic HSP90 complex in cancer. Nat Rev Cancer 10:537–549

    Article  CAS  PubMed  Google Scholar 

  • Tsukamoto S, Kuma A, Murakami M, Kishi C, Yamamoto A, Mizushima N (2008) Autophagy is essential for preimplantation development of mouse embryos. Science 321:117–120

    Article  CAS  PubMed  Google Scholar 

  • Waskiewicz AJ, Johnson JC, Penn B, Mahalingam M, Kimball SR, Cooper JA (1999) Phosphorylation of the cap-binding protein eukaryotic translation initiation factor 4E by protein kinase Mnk1 in vivo. Mol Cell Biol 19:1871–1880

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Westman BJ, Verheggen C, Hutten S, Lam YW, Bertrand E, Lamond AI (2010) A proteomic screen for nucleolar SUMO targets shows SUMOylation modulates the function of Nop5/Nop58. Mol Cell 39:618–631

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Willmund F, del Alamo M, Pechmann S, Chen T, Albanese V, Dammer EB, Peng J, Frydman J (2013) The cotranslational function of ribosome-associated Hsp70 in eukaryotic protein homeostasis. Cell 152:196–209

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wilson VG (2009) SUMO regulation of cellular processes. Springer, Dordrecht

    Book  Google Scholar 

  • Wohlschlegel JA, Johnson ES, Reed SI, Yates JR (2004) Global analysis of protein sumoylation in Saccharomyces cerevisiae. J Biol Chem 279:45662–45668

    Article  CAS  PubMed  Google Scholar 

  • Xu X, Vatsyayan J, Gao CX, Bakkenist CJ, Hu J (2010) Sumoylation of eIF4E activates mRNA translation. EMBO Rep 11:299–304

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yang Y, Fiskus W, Yong B, Atadja P, Takahashi Y, Pandita TK, Wang HG, Bhalla KN (2013) Acetylated hsp70 and KAP1-mediated Vps34 SUMOylation is required for autophagosome creation in autophagy. Proc Natl Acad Sci U S A 110:6841–6846

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yu JX, Zhang DY, Liu JY, Li JX, Yu YH, Wu XR, Huang CS (2012) RhoGDI SUMOylation at Lys-138 increases its binding activity to Rho GTPase and its inhibiting cancer cell motility. J Biol Chem 287:13752–13760

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhou W, Ryan JJ, Zhou H (2004) Global analyses of sumoylated proteins in Saccharomyces cerevisiae - Induction of protein sumoylation by cellular stresses. J Biol Chem 279:32262–32268

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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  1. Department of Molecular Cell Biology, Institute for Cancer Research, Oslo University Hospital and University of Oslo, Ullernchausseen 70, 0379, Oslo, Norway

    Jorrit M. Enserink

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Correspondence to Jorrit M. Enserink .

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  1. Department of Microbial Pathogenesis and Immunology, College of Medicine, Texas A&M Health Science Center, Bryan, Texas, USA

    Van G. Wilson

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Enserink, J.M. (2017). Regulation of Cellular Processes by SUMO: Understudied Topics. In: Wilson, V. (eds) SUMO Regulation of Cellular Processes. Advances in Experimental Medicine and Biology, vol 963. Springer, Cham. https://doi.org/10.1007/978-3-319-50044-7_5

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