SUMO1,2, and 3 are predominantly located in the nucleus and targets of SUMOylation are predominantly nuclear. Transcription cofactors are nuclear proteins that generally do not bind DNA themselves but interact with DNA-bound factors and influence transcription. SUMOylation of transcription cofactors usually inhibits the activity of the cofactor (reviewed in Girdwood et al. 2004, Gill 2005, Lyst and Stancheva 2007, Garcia-Dominguez and Reyes 2009). In the cases of coactivators such as PPARGC1A (PGC-1alpha) this results in decreased transcription; in the cases of corepressors such as MBD1 this results in increased transcription.
View original pathway at Reactome.
Blomster HA, Hietakangas V, Wu J, Kouvonen P, Hautaniemi S, Sistonen L.; ''Novel proteomics strategy brings insight into the prevalence of SUMO-2 target sites.''; PubMedEurope PMCScholia
Vennemann A, Hofmann TG.; ''SUMO regulates proteasome-dependent degradation of FLASH/Casp8AP2.''; PubMedEurope PMCScholia
Matafora V, D'Amato A, Mori S, Blasi F, Bachi A.; ''Proteomics analysis of nucleolar SUMO-1 target proteins upon proteasome inhibition.''; PubMedEurope PMCScholia
Zeng L, Yap KL, Ivanov AV, Wang X, Mujtaba S, Plotnikova O, Rauscher FJ, Zhou MM.; ''Structural insights into human KAP1 PHD finger-bromodomain and its role in gene silencing.''; PubMedEurope PMCScholia
Mascle XH, Germain-Desprez D, Huynh P, Estephan P, Aubry M.; ''Sumoylation of the transcriptional intermediary factor 1beta (TIF1beta), the Co-repressor of the KRAB Multifinger proteins, is required for its transcriptional activity and is modulated by the KRAB domain.''; PubMedEurope PMCScholia
Oh Y, Chung KC.; ''UHRF2, a ubiquitin E3 ligase, acts as a small ubiquitin-like modifier E3 ligase for zinc finger protein 131.''; PubMedEurope PMCScholia
Jacobs AM, Nicol SM, Hislop RG, Jaffray EG, Hay RT, Fuller-Pace FV.; ''SUMO modification of the DEAD box protein p68 modulates its transcriptional activity and promotes its interaction with HDAC1.''; PubMedEurope PMCScholia
Puigserver P, Wu Z, Park CW, Graves R, Wright M, Spiegelman BM.; ''A cold-inducible coactivator of nuclear receptors linked to adaptive thermogenesis.''; PubMedEurope PMCScholia
Uchimura Y, Ichimura T, Uwada J, Tachibana T, Sugahara S, Nakao M, Saitoh H.; ''Involvement of SUMO modification in MBD1- and MCAF1-mediated heterochromatin formation.''; PubMedEurope PMCScholia
Su HL, Li SS.; ''Molecular features of human ubiquitin-like SUMO genes and their encoded proteins.''; PubMedEurope PMCScholia
Knutti D, Kaul A, Kralli A.; ''A tissue-specific coactivator of steroid receptors, identified in a functional genetic screen.''; 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
Alm-Kristiansen AH, Norman IL, Matre V, Gabrielsen OS.; ''SUMO modification regulates the transcriptional activity of FLASH.''; PubMedEurope PMCScholia
Liu X, Liu Z, Jang SW, Ma Z, Shinmura K, Kang S, Dong S, Chen J, Fukasawa K, Ye K.; ''Sumoylation of nucleophosmin/B23 regulates its subcellular localization, mediating cell proliferation and survival.''; PubMedEurope PMCScholia
Ythier D, Larrieu D, Binet R, Binda O, Brambilla C, Gazzeri S, Pedeux R.; ''Sumoylation of ING2 regulates the transcription mediated by Sin3A.''; PubMedEurope PMCScholia
Lyst MJ, Nan X, Stancheva I.; ''Regulation of MBD1-mediated transcriptional repression by SUMO and PIAS proteins.''; PubMedEurope PMCScholia
Fan J, Ren H, Fei E, Jia N, Ying Z, Jiang P, Wu M, Wang G.; ''Sumoylation is critical for DJ-1 to repress p53 transcriptional activity.''; PubMedEurope PMCScholia
Ivanov AV, Peng H, Yurchenko V, Yap KL, Negorev DG, Schultz DC, Psulkowski E, Fredericks WJ, White DE, Maul GG, Sadofsky MJ, Zhou MM, Rauscher FJ.; ''PHD domain-mediated E3 ligase activity directs intramolecular sumoylation of an adjacent bromodomain required for gene silencing.''; PubMedEurope PMCScholia
Liu HW, Banerjee T, Guan X, Freitas MA, Parvin JD.; ''The chromatin scaffold protein SAFB1 localizes SUMO-1 to the promoters of ribosomal protein genes to facilitate transcription initiation and splicing.''; PubMedEurope PMCScholia
Merrill JC, Melhuish TA, Kagey MH, Yang SH, Sharrocks AD, Wotton D.; ''A role for non-covalent SUMO interaction motifs in Pc2/CBX4 E3 activity.''; PubMedEurope PMCScholia
Jang MS, Ryu SW, Kim E.; ''Modification of Daxx by small ubiquitin-related modifier-1.''; PubMedEurope PMCScholia
Girdwood D, Bumpass D, Vaughan OA, Thain A, Anderson LA, Snowden AW, Garcia-Wilson E, Perkins ND, Hay RT.; ''P300 transcriptional repression is mediated by SUMO modification.''; PubMedEurope PMCScholia
Lin DY, Huang YS, Jeng JC, Kuo HY, Chang CC, Chao TT, Ho CC, Chen YC, Lin TP, Fang HI, Hung CC, Suen CS, Hwang MJ, Chang KS, Maul GG, Shih HM.; ''Role of SUMO-interacting motif in Daxx SUMO modification, subnuclear localization, and repression of sumoylated transcription factors.''; PubMedEurope PMCScholia
Mooney SM, Grande JP, Salisbury JL, Janknecht R.; ''Sumoylation of p68 and p72 RNA helicases affects protein stability and transactivation potential.''; PubMedEurope PMCScholia
Pungaliya P, Kulkarni D, Park HJ, Marshall H, Zheng H, Lackland H, Saleem A, Rubin EH.; ''TOPORS functions as a SUMO-1 E3 ligase for chromatin-modifying proteins.''; PubMedEurope PMCScholia
Shinbo Y, Niki T, Taira T, Ooe H, Takahashi-Niki K, Maita C, Seino C, Iguchi-Ariga SM, Ariga H.; ''Proper SUMO-1 conjugation is essential to DJ-1 to exert its full activities.''; PubMedEurope PMCScholia
Oh Y, Chung KC.; ''Small ubiquitin-like modifier (SUMO) modification of zinc finger protein 131 potentiates its negative effect on estrogen signaling.''; PubMedEurope PMCScholia
Yang SH, Sharrocks AD.; ''The SUMO E3 ligase activity of Pc2 is coordinated through a SUMO interaction motif.''; PubMedEurope PMCScholia
Takahashi K, Taira T, Niki T, Seino C, Iguchi-Ariga SM, Ariga H.; ''DJ-1 positively regulates the androgen receptor by impairing the binding of PIASx alpha to the receptor.''; PubMedEurope PMCScholia
Chauchereau A, Amazit L, Quesne M, Guiochon-Mantel A, Milgrom E.; ''Sumoylation of the progesterone receptor and of the steroid receptor coactivator SRC-1.''; PubMedEurope PMCScholia
Rytinki MM, Palvimo JJ.; ''SUMOylation modulates the transcription repressor function of RIP140.''; PubMedEurope PMCScholia
Girdwood DW, Tatham MH, Hay RT.; ''SUMO and transcriptional regulation.''; PubMedEurope PMCScholia
Garcia-Dominguez M, Reyes JC.; ''SUMO association with repressor complexes, emerging routes for transcriptional control.''; PubMedEurope PMCScholia
Lalioti VS, Vergarajauregui S, Pulido D, Sandoval IV.; ''The insulin-sensitive glucose transporter, GLUT4, interacts physically with Daxx. Two proteins with capacity to bind Ubc9 and conjugated to SUMO1.''; PubMedEurope PMCScholia
Kagey MH, Melhuish TA, Wotton D.; ''The polycomb protein Pc2 is a SUMO E3.''; 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
Gresko E, Möller A, Roscic A, Schmitz ML.; ''Covalent modification of human homeodomain interacting protein kinase 2 by SUMO-1 at lysine 25 affects its stability.''; PubMedEurope PMCScholia
Li X, Lee YK, Jeng JC, Yen Y, Schultz DC, Shih HM, Ann DK.; ''Role for KAP1 serine 824 phosphorylation and sumoylation/desumoylation switch in regulating KAP1-mediated transcriptional repression.''; 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
Alm-Kristiansen AH, Lorenzo PI, Molværsmyr AK, Matre V, Ledsaak M, Sæther T, Gabrielsen OS.; ''PIAS1 interacts with FLASH and enhances its co-activation of c-Myb.''; PubMedEurope PMCScholia
Hofmann TG, Jaffray E, Stollberg N, Hay RT, Will H.; ''Regulation of homeodomain-interacting protein kinase 2 (HIPK2) effector function through dynamic small ubiquitin-related modifier-1 (SUMO-1) modification.''; PubMedEurope PMCScholia
Lee YK, Thomas SN, Yang AJ, Ann DK.; ''Doxorubicin down-regulates Kruppel-associated box domain-associated protein 1 sumoylation that relieves its transcription repression on p21WAF1/CIP1 in breast cancer MCF-7 cells.''; PubMedEurope PMCScholia
Lyst MJ, Stancheva I.; ''A role for SUMO modification in transcriptional repression and activation.''; PubMedEurope PMCScholia
Hoffmann et al. 2005 (205) and Gresko et al. (2005) cite lysine-25 as the SUMO-modified residue, however the motif in their papers indicates lysine-32 of the UniProt sequence is the lysine residue modified.
CBX4 (Pc2) via its SUMO-interacting motifs recruits both CTBP1 and SUMO2,3:UBE2I (SUMO1:UBC9) to polycomb bodies where CTBP1 is SUMOylated with SUMO2,3 at lysine-428, as inferred from SUMOylation with SUMO1 (Merrill et al. 2010, Yang and Sharrocks 2010).
CBX4 (Pc2) via its SUMO-interacting motifs recruits both CTBP1 and SUMO1:UBE2I (SUMO1:UBC9) to polycomb bodies where CTBP1 is SUMOylated with SUMO1 at lysine-428 (Kagey et al. 2003, Merrill et al. 2010, Yang and Sharrocks 2010).
CBX4 (Pc2) and UHRF2 are able to SUMOylate ZNF131 on lysine-601 (lysine-567 in the isoform in Oh and Chung 2012, Oh and Chung 2013) . SUMOylation of ZNF131 increases the inhibition of ERalpha signaling by ZNF131 through suppression of ERalpha homodimerization.
The PHD domain of TRIM28 (KAP1) acts as a SUMO E3 ligase to SUMOylate the bromodomain of TRIM28 with SUMO1 (Ivanov et al. 2007, Lee et al. 2007, Li et al. 2007, Mascle et al. 2007, Zeng et al. 2008, Impens et al. 2014). SUMOylation enhances repression of p21 transcription by the TRIM28:ZNF350 (KAP1:ZBRK1) complex. SUMOylated TRIM28 recruits SETDB1 and CHD3 (of the NuRD complex).
EP300 (p300) is SUMOylated at lysine-1020 and lysine-1024 with SUMO1 (Girdwood et al. 2003). SUMOylation of EP300 alleviates transcriptional repression caused by the CRD1 domain.
DDX17 is SUMOylated at lysine-50 with SUMO1 or SUMO2 (Mooney et al. 2010, Fuller-Pace and Nicol 2012, Impens et al. 2014). SUMOylation reduces the transactivation activity of DDX17 with the estrogen receptor and with p53. SUMOylation also promotes association of DDX17 with HDAC1.
MKL1 is SUMOylated with SUMO1 at lysine-499, lysine-576, and lysine-624 (Nakagawa and Kuzumaki 2005) SUMOylation represses transcriptional activity of MKL1. MKL1 is a coactivator of SRF.
DDX5 is SUMOylated at lysine-53 with SUMO1 (Mooney et al. 2010, Matafora et al. 2009, Impens et al. 2014). SUMOylation enhances coactivation activity of DDX5, stability of DDX5, and interaction of DDX5 with HDAC1.
PIAS1 SUMOylates DDX5 at lysine-53 with SUMO2 (Jacobs et al. 2007, Hendriks et al. 2014, Impens et al. 2014). SUMOylation reduces the coactivation activity of DDX5 with p53 but enhances coactivation of the estrogen receptor. SUMOylation also increases stability of DDX5 and promotes interaction of DDX5 with HDAC1. DDX5 is a coactivator of p53 (TP53).
As infered from mouse homologs, PPARGC1A (PGC-1alpha) is SUMOylated at lysine-184 with SUMO1. SUMOylation reduces transcription activation by PPARGC1A.
The CBX3 component of PRC1 SUMOylates CASP8AP2 (FLASH) at lysine-1813 with SUMO1 (Alm-Kristiansen et al. 2009). SUMOylation enhances the transcriptional coactivation activity of CASP8AP2. SUMOylation also appears to trigger proteasomal degradation of CASP8AP2 (Vennemann and Hofmann 2013).
As inferred from mouse homologs, CREBBP (CBP) is SUMOylated at lysine-998, lysine-1033, and lysine-1056 with SUMO1. SUMOylation recruits DAXX and HDAC2 to repress transcription.
NCOA1 (SRC1) is SUMOylated at lysine-732 and lysine-774 with SUMO1 (Chauchereau et al. 2003). SUMOylation enhances interaction between NCOA1 and the progesterone receptor and causes NCOA1 to be retained in the nucleus.
As inferred from mouse homologs, NCOA2 is SUMOylated at lysine-239, lysine-731, and lysine-788 with SUMO1. SUMOylation of NCOA2 increases coactivation of transcription by the androgen receptor.
PIAS2-1 (PIASxalpha) SUMOylates PARK7 (DJ-1) at lysine-130 with SUMO1 (Takahashi et al. 2001, Shinbo et al. 2006). SUMOylation causes PARK7 to be retained in the nucleus where it represses transcription activation by P53 (TP53). A non-SUMOylatable mutant of PARK7 is located in the cytoplasm and fails to repress TP53 (p53) transcriptional activity (Fan et al. 2008).
PIAS1 SUMOylates SAFB at lysine-231 and lysine-294 with SUMO1 (Garee et al. 2011). SUMOylation of SAFB is required for co-repressor activity of SAFB at promoters regulated by the estrogen receptor (ER). In contrast, SUMOylated SAFB increases transcription of genes encoding ribosomal proteins (Liu 2015).
DAXX is SUMOylated at lysine-630 and lysine-631 with SUMO1 (Jang et al. 2002, Lalioti et al. 2002, Lin et al. 2006). SUMOylation of DAXX does not prevent it from localizing to PML oncogenic domains.
PIAS1,3 SUMOylate NRIP1 (RIP140) at lysine 756 and lysine-1154 with SUMO1 (Rytinki et al. 2008). SUMOylation enhances transcription repression by NRIP1.
NPM1 (Nucleophosmin, B23) is SUMOylated at lysine-263 with SUMO2,3 (Liu et al. 2007, Blomster et al. 2009, Hendriks et al. 2014). SUMOylation enhances binding of NPM1 to Rb and enhances nuclear residency of NPM1.
NPM1 (Nucleophosmin, B23) is SUMOylated at lysine-263 with SUMO1 (Liu et al. 2007). SUMOylation enhances binding of NPM1 to Rb and enhances nuclear residency of NPM1.
HIPK2 is SUMOylated at lysine-32 with SUMO1. (Lysine-25 is cited by Hofmann et al. 2005 and Gresko et al. 2005, however the sequence motif listed in Hoffmann et al. 2005 corresponds to lysine-32 of the UniProt reference protein. An alternative isoform having lysine-25 is listed as accession AAG35710 in GenBank.) SUMOylation of HIPK2 disrupts interaction of HIPK2 with GROUCHO corepressor, inhibits JNK activation, and inhibits p53-independent antiproliferative function.
PIAS1,3 SUMOylates MBD1 at lysine-499 and lysine-538 of the reference sequence (lysine-450 and lysine-489 of isoform 5) with SUMO1 (Lyst et al. 2006, Uchimura et al. 2006). SUMOylated MBD1 does not form a complex with SETDB1 and does not repress transcription.
PIAS1, PIAS4 SUMOylate CASP8AP2 (FLASH) at lysine-1813 with SUMO1 (Alm-Kristiansen et al. 2009, Alm-Kristiansen et al. 2011). SUMOylation enhances the transcriptional coactivation activity of CASP8AP2. As inferred from mouse homologs, SUMOylation also appears to trigger proteasomal degradation of CASP8AP2 (Vennemann and Hofmann 2013).
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