SUMOylation of transcription factors (Homo sapiens)

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3, 4, 13, 14, 22...122, 6, 7, 11, 15...6, 7, 11, 16, 19...5, 9, 161, 2010nucleoplasmPIAS1,3,4SUMO1-C93-UBE2I PIAS3 TP53SUMO1-K551-SP3 UBE2I:SUMO2,UBE2I:SUMO3MDM2 SUMO2-C93-UBE2I SUMO2,3-K386-TP53SUMO1:C93-UBE2ISUMO1-K-TP53BP1 UBE2ISUMO1:TP53BP1SP3SUMO2,3-K509-MTA1MTA1SUMO2-C93-UBE2I PIAS4 SUMO1-K289,423-MITF UBE2IMITFPIAS4UBE2I-G92-SUMO3 UBE2I-G93-SUMO2 K423-MITF-G97-SUMO1 SUMO3-C93-UBE2I TP53BP1-G97-SUMO1 SUMO2-C93-UBE2I UBE2I2SUMO1:MITFPIAS3UBE2I-G92-SUMO3 p14-ARF:MDM2K289-MITF-G97-SUMO1 SUMO3-C93-UBE2I UBE2I-G97-SUMO1 UBE2IUBE2ISUMO2-K551-SP3SUMO1-C93-UBE2I UBE2I-G93-SUMO2 UBE2I-G97-SUMO1 UBE2IUBE2I:SUMO2,UBE2I:SUMO3SUMO1:C93-UBE2IUBE2I-G93-SUMO2 PIAS1SUMO1:SP3SUMO1-C93-UBE2I SUMO1:C93-UBE2IPIAS1 p14-ARF TP53BP1UBE2I-G97-SUMO1 SUMO2:UBE2ISP3-G97-SUMO1 21208, 215, 9, 168, 218, 2112021


Description

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). View original pathway at:Reactome.

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Bibliography

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  2. Stindt MH, Carter S, Vigneron AM, Ryan KM, Vousden KH.; ''MDM2 promotes SUMO-2/3 modification of p53 to modulate transcriptional activity.''; PubMed Europe PMC Scholia
  3. Garcia-Dominguez M, Reyes JC.; ''SUMO association with repressor complexes, emerging routes for transcriptional control.''; PubMed Europe PMC Scholia
  4. 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.''; PubMed Europe PMC Scholia
  5. 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.''; PubMed Europe PMC Scholia
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  7. Lyst MJ, Stancheva I.; ''A role for SUMO modification in transcriptional repression and activation.''; PubMed Europe PMC Scholia
  8. 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.''; PubMed Europe PMC Scholia
  9. Eloranta JJ, Hurst HC.; ''Transcription factor AP-2 interacts with the SUMO-conjugating enzyme UBC9 and is sumolated in vivo.''; PubMed Europe PMC Scholia
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  11. Lomelí H, Vázquez M.; ''Emerging roles of the SUMO pathway in development.''; PubMed Europe PMC Scholia
  12. Impens F, Radoshevich L, Cossart P, Ribet D.; ''Mapping of SUMO sites and analysis of SUMOylation changes induced by external stimuli.''; PubMed Europe PMC Scholia
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  14. Sapetschnig A, Rischitor G, Braun H, Doll A, Schergaut M, Melchior F, Suske G.; ''Transcription factor Sp3 is silenced through SUMO modification by PIAS1.''; PubMed Europe PMC Scholia
  15. Sapetschnig A, Koch F, Rischitor G, Mennenga T, Suske G.; ''Complexity of translationally controlled transcription factor Sp3 isoform expression.''; PubMed Europe PMC Scholia
  16. Ouyang J, Valin A, Gill G.; ''Regulation of transcription factor activity by SUMO modification.''; PubMed Europe PMC Scholia
  17. Girdwood DW, Tatham MH, Hay RT.; ''SUMO and transcriptional regulation.''; PubMed Europe PMC Scholia
  18. 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.''; PubMed Europe PMC Scholia
  19. Berlato C, Chan KV, Price AM, Canosa M, Scibetta AG, Hurst HC.; ''Alternative TFAP2A isoforms have distinct activities in breast cancer.''; PubMed Europe PMC Scholia
  20. Stielow B, Sapetschnig A, Wink C, Krüger I, Suske G.; ''SUMO-modified Sp3 represses transcription by provoking local heterochromatic gene silencing.''; PubMed Europe PMC Scholia
  21. Kamitani T, Kito K, Nguyen HP, Fukuda-Kamitani T, Yeh ET.; ''Characterization of a second member of the sentrin family of ubiquitin-like proteins.''; PubMed Europe PMC Scholia
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  25. Gill G.; ''Something about SUMO inhibits transcription.''; PubMed Europe PMC Scholia
  26. Galisson F, Mahrouche L, Courcelles M, Bonneil E, Meloche S, Chelbi-Alix MK, Thibault P.; ''A novel proteomics approach to identify SUMOylated proteins and their modification sites in human cells.''; PubMed Europe PMC Scholia
  27. 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.''; PubMed Europe PMC Scholia
  28. 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.''; PubMed Europe PMC Scholia
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  30. Ellis DJ, Dehm SM, Bonham K.; ''The modification of Sp3 isoforms by SUMOylation has differential effects on the SRC1A promoter.''; PubMed Europe PMC Scholia
  31. 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.''; PubMed Europe PMC Scholia
  32. Miller AJ, Levy C, Davis IJ, Razin E, Fisher DE.; ''Sumoylation of MITF and its related family members TFE3 and TFEB.''; PubMed Europe PMC Scholia
  33. 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.''; PubMed Europe PMC Scholia
  34. Tammsalu T, Matic I, Jaffray EG, Ibrahim AFM, Tatham MH, Hay RT.; ''Proteome-wide identification of SUMO2 modification sites.''; PubMed Europe PMC Scholia
  35. Ross S, Best JL, Zon LI, Gill G.; ''SUMO-1 modification represses Sp3 transcriptional activation and modulates its subnuclear localization.''; PubMed Europe PMC Scholia

History

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CompareRevisionActionTimeUserComment
114895view16:40, 25 January 2021ReactomeTeamReactome version 75
113341view11:41, 2 November 2020ReactomeTeamReactome version 74
112551view15:51, 9 October 2020ReactomeTeamReactome version 73
101465view11:33, 1 November 2018ReactomeTeamreactome version 66
101003view21:12, 31 October 2018ReactomeTeamreactome version 65
100539view19:46, 31 October 2018ReactomeTeamreactome version 64
100086view16:31, 31 October 2018ReactomeTeamreactome version 63
99637view15:02, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
93954view13:47, 16 August 2017ReactomeTeamreactome version 61
93550view11:26, 9 August 2017ReactomeTeamreactome version 61
88422view11:54, 5 August 2016FehrhartOntology Term : 'sumoylation pathway' added !
86652view09:23, 11 July 2016ReactomeTeamNew pathway

External references

DataNodes

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NameTypeDatabase referenceComment
2SUMO1:MITFComplexR-HSA-3730749 (Reactome)
K289-MITF-G97-SUMO1 ProteinP63165 (Uniprot-TrEMBL)
K423-MITF-G97-SUMO1 ProteinP63165 (Uniprot-TrEMBL)
MDM2 ProteinQ00987 (Uniprot-TrEMBL)
MITFProteinO75030 (Uniprot-TrEMBL)
MTA1ProteinQ13330 (Uniprot-TrEMBL)
PIAS1 ProteinO75925 (Uniprot-TrEMBL)
PIAS1,3,4ComplexR-HSA-3465556 (Reactome)
PIAS1ProteinO75925 (Uniprot-TrEMBL)
PIAS3 ProteinQ9Y6X2 (Uniprot-TrEMBL)
PIAS3ProteinQ9Y6X2 (Uniprot-TrEMBL)
PIAS4 ProteinQ8N2W9 (Uniprot-TrEMBL)
PIAS4ProteinQ8N2W9 (Uniprot-TrEMBL)
SP3-G97-SUMO1 ProteinP63165 (Uniprot-TrEMBL)
SP3ProteinQ02447 (Uniprot-TrEMBL)
SUMO1-C93-UBE2I ProteinP63279 (Uniprot-TrEMBL)
SUMO1-K-TP53BP1 ProteinQ12888 (Uniprot-TrEMBL)
SUMO1-K289,423-MITF ProteinO75030 (Uniprot-TrEMBL)
SUMO1-K551-SP3 ProteinQ02447 (Uniprot-TrEMBL)
SUMO1:C93-UBE2IComplexR-HSA-2993783 (Reactome)
SUMO1:SP3ComplexR-HSA-3730656 (Reactome)
SUMO1:TP53BP1ComplexR-HSA-3730720 (Reactome)
SUMO2,3-K386-TP53ProteinP04637 (Uniprot-TrEMBL)
SUMO2,3-K509-MTA1ProteinQ13330 (Uniprot-TrEMBL)
SUMO2-C93-UBE2I ProteinP63279 (Uniprot-TrEMBL)
SUMO2-K551-SP3ProteinQ02447 (Uniprot-TrEMBL)
SUMO2:UBE2IComplexR-HSA-2993778 (Reactome)
SUMO3-C93-UBE2I ProteinP63279 (Uniprot-TrEMBL)
TP53BP1-G97-SUMO1 ProteinP63165 (Uniprot-TrEMBL)
TP53BP1ProteinQ12888 (Uniprot-TrEMBL)
TP53ProteinP04637 (Uniprot-TrEMBL)
UBE2I-G92-SUMO3 ProteinP55854 (Uniprot-TrEMBL)
UBE2I-G93-SUMO2 ProteinP61956 (Uniprot-TrEMBL)
UBE2I-G97-SUMO1 ProteinP63165 (Uniprot-TrEMBL)
UBE2I:SUMO2,UBE2I:SUMO3ComplexR-HSA-3899312 (Reactome)
UBE2IProteinP63279 (Uniprot-TrEMBL)
p14-ARF ProteinQ8N726 (Uniprot-TrEMBL)
p14-ARF:MDM2ComplexR-HSA-3209192 (Reactome)

Annotated Interactions

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SourceTargetTypeDatabase referenceComment
2SUMO1:MITFArrowR-HSA-3232162 (Reactome)
MITFR-HSA-3232162 (Reactome)
MTA1R-HSA-3465545 (Reactome)
PIAS1,3,4mim-catalysisR-HSA-3465545 (Reactome)
PIAS1mim-catalysisR-HSA-3247493 (Reactome)
PIAS1mim-catalysisR-HSA-6804468 (Reactome)
PIAS3mim-catalysisR-HSA-3232162 (Reactome)
PIAS4mim-catalysisR-HSA-2997723 (Reactome)
R-HSA-2997706 (Reactome) 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).
R-HSA-2997723 (Reactome) 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.
R-HSA-3232162 (Reactome) 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.
R-HSA-3247493 (Reactome) 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).
R-HSA-3465545 (Reactome) 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).
R-HSA-6804468 (Reactome) 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).
SP3R-HSA-3247493 (Reactome)
SP3R-HSA-6804468 (Reactome)
SUMO1:C93-UBE2IR-HSA-2997723 (Reactome)
SUMO1:C93-UBE2IR-HSA-3232162 (Reactome)
SUMO1:C93-UBE2IR-HSA-3247493 (Reactome)
SUMO1:SP3ArrowR-HSA-3247493 (Reactome)
SUMO1:TP53BP1ArrowR-HSA-2997723 (Reactome)
SUMO2,3-K386-TP53ArrowR-HSA-2997706 (Reactome)
SUMO2,3-K509-MTA1ArrowR-HSA-3465545 (Reactome)
SUMO2-K551-SP3ArrowR-HSA-6804468 (Reactome)
SUMO2:UBE2IR-HSA-6804468 (Reactome)
TP53BP1R-HSA-2997723 (Reactome)
TP53R-HSA-2997706 (Reactome)
UBE2I:SUMO2,UBE2I:SUMO3R-HSA-2997706 (Reactome)
UBE2I:SUMO2,UBE2I:SUMO3R-HSA-3465545 (Reactome)
UBE2IArrowR-HSA-2997706 (Reactome)
UBE2IArrowR-HSA-2997723 (Reactome)
UBE2IArrowR-HSA-3232162 (Reactome)
UBE2IArrowR-HSA-3247493 (Reactome)
UBE2IArrowR-HSA-3465545 (Reactome)
UBE2IArrowR-HSA-6804468 (Reactome)
p14-ARF:MDM2mim-catalysisR-HSA-2997706 (Reactome)
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