Proteins classified as transcription factors constitute a disproportionate number of SUMOylation targets. In most cases SUMOylation inhibits transcriptional activation, however in some cases such as TP53 (p53) SUMOylation can enhance activation. Inhibition of transcription by SUMOylation may be due to interference with DNA binding, re-localization to inactive nuclear bodies, or recruitment of repressive cofactors such as histone deacetylases (reviewed in Girdwood et al. 2004, Gill 2005).
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Su HL, Li SS.; ''Molecular features of human ubiquitin-like SUMO genes and their encoded proteins.''; PubMedEurope PMCScholia
Stindt MH, Carter S, Vigneron AM, Ryan KM, Vousden KH.; ''MDM2 promotes SUMO-2/3 modification of p53 to modulate transcriptional activity.''; PubMedEurope PMCScholia
Garcia-Dominguez M, Reyes JC.; ''SUMO association with repressor complexes, emerging routes for transcriptional control.''; PubMedEurope PMCScholia
Dehennaut V, Loison I, Dubuissez M, Nassour J, Abbadie C, Leprince D.; ''DNA double-strand breaks lead to activation of hypermethylated in cancer 1 (HIC1) by SUMOylation to regulate DNA repair.''; PubMedEurope PMCScholia
Kim JH, Kim YH, Kim HM, Park HO, Ha NC, Kim TH, Park M, Lee K, Bae J.; ''FOXL2 posttranslational modifications mediated by GSK3β determine the growth of granulosa cell tumours.''; PubMedEurope PMCScholia
Paget S, Dubuissez M, Dehennaut V, Nassour J, Harmon BT, Spruyt N, Loison I, Abbadie C, Rood BR, Leprince D.; ''HIC1 (hypermethylated in cancer 1) SUMOylation is dispensable for DNA repair but is essential for the apoptotic DNA damage response (DDR) to irreparable DNA double-strand breaks (DSBs).''; PubMedEurope PMCScholia
Lyst MJ, Stancheva I.; ''A role for SUMO modification in transcriptional repression and activation.''; PubMedEurope PMCScholia
Spengler ML, Kennett SB, Moorefield KS, Simmons SO, Brattain MG, Horowitz JM.; ''Sumoylation of internally initiated Sp3 isoforms regulates transcriptional repression via a Trichostatin A-insensitive mechanism.''; PubMedEurope PMCScholia
Eloranta JJ, Hurst HC.; ''Transcription factor AP-2 interacts with the SUMO-conjugating enzyme UBC9 and is sumolated in vivo.''; PubMedEurope PMCScholia
Bogachek MV, Chen Y, Kulak MV, Woodfield GW, Cyr AR, Park JM, Spanheimer PM, Li Y, Li T, Weigel RJ.; ''Sumoylation pathway is required to maintain the basal breast cancer subtype.''; PubMedEurope PMCScholia
Lomelí H, Vázquez M.; ''Emerging roles of the SUMO pathway in development.''; PubMedEurope PMCScholia
Impens F, Radoshevich L, Cossart P, Ribet D.; ''Mapping of SUMO sites and analysis of SUMOylation changes induced by external stimuli.''; PubMedEurope PMCScholia
Stankovic-Valentin N, Deltour S, Seeler J, Pinte S, Vergoten G, Guérardel C, Dejean A, Leprince D.; ''An acetylation/deacetylation-SUMOylation switch through a phylogenetically conserved psiKXEP motif in the tumor suppressor HIC1 regulates transcriptional repression activity.''; PubMedEurope PMCScholia
Sapetschnig A, Rischitor G, Braun H, Doll A, Schergaut M, Melchior F, Suske G.; ''Transcription factor Sp3 is silenced through SUMO modification by PIAS1.''; PubMedEurope PMCScholia
Ouyang J, Valin A, Gill G.; ''Regulation of transcription factor activity by SUMO modification.''; PubMedEurope PMCScholia
Girdwood DW, Tatham MH, Hay RT.; ''SUMO and transcriptional regulation.''; PubMedEurope PMCScholia
Marongiu M, Deiana M, Meloni A, Marcia L, Puddu A, Cao A, Schlessinger D, Crisponi L.; ''The forkhead transcription factor Foxl2 is sumoylated in both human and mouse: sumoylation affects its stability, localization, and activity.''; PubMedEurope PMCScholia
Berlato C, Chan KV, Price AM, Canosa M, Scibetta AG, Hurst HC.; ''Alternative TFAP2A isoforms have distinct activities in breast cancer.''; PubMedEurope PMCScholia
Stielow B, Sapetschnig A, Wink C, Krüger I, Suske G.; ''SUMO-modified Sp3 represses transcription by provoking local heterochromatic gene silencing.''; PubMedEurope PMCScholia
Kamitani T, Kito K, Nguyen HP, Fukuda-Kamitani T, Yeh ET.; ''Characterization of a second member of the sentrin family of ubiquitin-like proteins.''; PubMedEurope PMCScholia
Galanty Y, Belotserkovskaya R, Coates J, Polo S, Miller KM, Jackson SP.; ''Mammalian SUMO E3-ligases PIAS1 and PIAS4 promote responses to DNA double-strand breaks.''; PubMedEurope PMCScholia
Hendriks IA, D'Souza RC, Chang JG, Mann M, Vertegaal AC.; ''System-wide identification of wild-type SUMO-2 conjugation sites.''; PubMedEurope PMCScholia
Kuo FT, Bentsi-Barnes IK, Barlow GM, Bae J, Pisarska MD.; ''Sumoylation of forkhead L2 by Ubc9 is required for its activity as a transcriptional repressor of the Steroidogenic Acute Regulatory gene.''; PubMedEurope PMCScholia
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Cong L, Pakala SB, Ohshiro K, Li DQ, Kumar R.; ''SUMOylation and SUMO-interacting motif (SIM) of metastasis tumor antigen 1 (MTA1) synergistically regulate its transcriptional repressor function.''; PubMedEurope PMCScholia
Stielow B, Sapetschnig A, Krüger I, Kunert N, Brehm A, Boutros M, Suske G.; ''Identification of SUMO-dependent chromatin-associated transcriptional repression components by a genome-wide RNAi screen.''; PubMedEurope PMCScholia
Van Rechem C, Boulay G, Pinte S, Stankovic-Valentin N, Guérardel C, Leprince D.; ''Differential regulation of HIC1 target genes by CtBP and NuRD, via an acetylation/SUMOylation switch, in quiescent versus proliferating cells.''; PubMedEurope PMCScholia
Ellis DJ, Dehm SM, Bonham K.; ''The modification of Sp3 isoforms by SUMOylation has differential effects on the SRC1A promoter.''; PubMedEurope PMCScholia
Hendriks IA, D'Souza RC, Yang B, Verlaan-de Vries M, Mann M, Vertegaal AC.; ''Uncovering global SUMOylation signaling networks in a site-specific manner.''; PubMedEurope PMCScholia
Miller AJ, Levy C, Davis IJ, Razin E, Fisher DE.; ''Sumoylation of MITF and its related family members TFE3 and TFEB.''; PubMedEurope PMCScholia
Georges A, Benayoun BA, Marongiu M, Dipietromaria A, L'Hôte D, Todeschini AL, Auer J, Crisponi L, Veitia RA.; ''SUMOylation of the Forkhead transcription factor FOXL2 promotes its stabilization/activation through transient recruitment to PML bodies.''; PubMedEurope PMCScholia
Tammsalu T, Matic I, Jaffray EG, Ibrahim AFM, Tatham MH, Hay RT.; ''Proteome-wide identification of SUMO2 modification sites.''; PubMedEurope PMCScholia
Ross S, Best JL, Zon LI, Gill G.; ''SUMO-1 modification represses Sp3 transcriptional activation and modulates its subnuclear localization.''; PubMedEurope PMCScholia
MDM2 in a complex with CDKN2A (p14-ARF) SUMOylates TP53 (p53) with SUMO2,3 at lysine-386 (Stindt et al. 2011, Hendriks et al. 2014, Tammsalu et al. 2014). SUMOylation decreases transcriptional activation by TP53 at some genes and decreases repression by TP53 at other genes (Stindt et al. 2011).
PIAS4 SUMOylates TP53BP1 with SUMO1 in response to double-strand breaks in DNA (Galanty et al. 2009, Impens et al. 2014). Overall, like TP53BP1, SUMO1,2,3, UBE2I, PIAS1 and PIAS4 are all observed to accumulate at double-strand breaks.
PIAS3 SUMOylates MITF with SUMO1 at lysine-289 and lysine-423 (lysine-182 and lysine-316 of the M2 isoform, Miller et al. 2005). SUMOylation reduces transcriptional activation by MITF at promoters containing multiple binding sites for MITF.
UBE2I (UBC9) interacts with TFAP2A, TFAP2B and TFAP2C, and the interaction site has been mapped to the C terminal region of TFAP2C; SUMOylation occurs on lysine-10 (Eloranta and Hurst 2002). As lysine-10 is conserved in TFAP2A and TFAP2B, SUMOylation of these factors is assumed to be on lysine-10 (Eloranta and Hurst 2002; Impens et al. 2014). SUMOylation causes a reduction in AP-2 transcriptional activation function but is required for its repressive function. A dominant negative mutant of UBC9 led to increased activation and reduced repressor function of TFAP2A and C, supporting the role of UBC9 in SUMOylation (Eloranta and Hurst 2002; Berlato et al. 2011). Isoform 1a of TFAP2A is SUMOylated, isoforms 1b and 1c lack lysine 10 and are not SUMOylated (Berlato et al. 2011). TFAP2D and TFAP2E lack lysine-10 and are thus assumed not to be SUMOylated. SUMOylation of TFAP2A blocked its ability to induce the expression of luminal genes and repression of basal genes (Bogachek et al. 2014). Disruption of the sumoylation pathway by knockdown of sumoylation enzymes, mutation of the SUMO-target lysine of TFAP2A, or treatment with sumoylation inhibitors induced MET in basal breast cancers, which was dependent on TFAP2A(Bogachek et al. 2014).
UBE2I (UBC9) interacts with the C terminal region of TFAP2B (Eloranta and Hurst 2002). As inferred from TFAP2C, SUMOylation of TFAP2B occurs at lysine in the VKYE motif and. therefore UBC9 is assumed to catalyze the ligation of SUMO1 to TFAP2B.
UBE2I (UBC9) interacts with the C-terminal region of TFAP2C (Eloranta and Hurst 2002). SUMOylation of TFAP2C occurs at lysine-10 and causes a reduction in its transcriptional activation activity. A dominant negative mutant of UBC9 led to increased activity of TFAP2C therefore UBC9 is assumed to catalyze the ligation of SUMO1 to TFAP2C.
PIAS1 SUMOylates SP3 with SUMO1 at lysine-551 (Ross et al. 2002, Sapetschnig et al. 2002, Sapetschnig et al. 2004, Spengler et al. 2005, Ellis et al. 2006, Impens et al. 2014). A minor amount of SUMOylation is also observed at lysine-120 (Ross et al. 2002). The effects of SUMOylation on the activities of isoforms of SP3 are promoter-dependent (Sapetschnig et al. 2004). Generally SUMOylation reduces the transcription activation capacity of the long and the short isoforms of Sp3 (Ross et al. 2002, Sapetschnig et al 2004, Ellis et al 2006). Mechanistically, SUMO attachment to Sp3 serves as a molecular beacon for the recruitment of chromatin-modifying machineries that impose epigenetic silencing (inferred from Drosophila homologs in Stielow et al. 2008a, inferred from mouse homologs in Stielow et al. 2008b).
PIAS1,3,4 SUMOylate MTA1 with SUMO2,3 at lysine-509 (Cong et al. 2011). SUMOylation increases the repressor activity of MTA1 at the PS2 promoter (Cong et al. 2011).
UBC9 and PIAS1 SUMOylate FOXL2 with SUMO1 (Kuo et al. 2009, Marongiu et al 2010, Georges et al. 2011). This modification changes its cellular localization, stability and transcriptional activity (Marongiu et al, 2010). SUMOylation localizes FOXL2 to PML bodies in the nucleus. SUMOylation is required for repression of transcription by FOXL2 at the StAR promoter and reduces transactivation by FOXL2 at the PER2 promoter. Hypophosphorylation of serine-33 correlates with SUMOylation and stablization of FOXL2, leading to enhanced transcriptional activation of TNF-R1, FAS, caspase 8, p21, and aromatase (Kim et al. 2014).
PIAS1,2-1 SUMOylate deacetylated HIC1 at lysine-333 (lysine 314 of HIC1 isoform 2) with SUMO1 (Stankovic-Valentin et al. 2007). Acetylation of HIC1 at lysine-333 inhibits SUMOylation. SUMOylation increases transcription repression by HIC1 (Stankovic-Valentin et al. 2007) and favors the interaction of HIC1 with MTA1 (Van Rechem et al., Mol Cell Biol, 2010) and MTA3 (Paget et al. 2016) notably during the DNA damage response (DDR) to non-repairable double strand breaks (DSBs).(Dehennaut et al. 2013). This increase of HIC1 SUMOylation during the DDR to DSBs is strictly dependent on the ATM kinase (Paget et al. 2016). SUMOylation of HIC1 is dispensable for DNA repair since the non-SUMOylatable point mutant E316A is as efficient as wt HIC1 in Comet assays which measure the repair of DSBs (Paget et al. 2016).
PIAS1 SUMOylates SP3 with SUMO2 at lysine-551 (Sapetschnig et al. 2002, Galisson et al. 2011, Tammsalu et al. 2014, Hendriks et al. 2015). SUMOylation reduces the transcription activation capacity of the long and the short isoforms of Sp3 (Sapetschnig et al 2004). Mechanistically, SUMO attachment to Sp3 serves as a molecular beacon for the recruitment of chromatin-modifying machineries that impose epigenetic silencing (inferred from Drosophila homologs in Stielow et al. 2008a, inferred from mouse homologs in Stielow et al. 2008b).
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