NF-kappaB transcription factors are sequestered in the cytosol due to their association with IkappaB. During activation of NF-kappaB, IKK phosphorylates IkappaB, releasing NF-kappaB for importation into the nucleus. NF-kappaB transcription factors, the NFKBIA component of IkappaB, and subunits of the IKK complex can be SUMOylated (reviewed in Kracklauer and Schmidt 2003, Liu et al. 2013). SUMOylations of IkappaB, NFKBIA, and RELA inhibit NF-kappaB signaling; SUMOylation of NFKB2 is required for proteolytic processing.
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Kracklauer MP, Schmidt C.; ''At the crossroads of SUMO and NF-kappaB.''; PubMedEurope PMCScholia
Desterro JM, Rodriguez MS, Hay RT.; ''SUMO-1 modification of IkappaBalpha inhibits NF-kappaB activation.''; 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
Su HL, Li SS.; ''Molecular features of human ubiquitin-like SUMO genes and their encoded proteins.''; PubMedEurope PMCScholia
Huang TT, Wuerzberger-Davis SM, Wu ZH, Miyamoto S.; ''Sequential modification of NEMO/IKKgamma by SUMO-1 and ubiquitin mediates NF-kappaB activation by genotoxic stress.''; PubMedEurope PMCScholia
Rodriguez MS, Dargemont C, Hay RT.; ''SUMO-1 conjugation in vivo requires both a consensus modification motif and nuclear targeting.''; PubMedEurope PMCScholia
Vatsyayan J, Qing G, Xiao G, Hu J.; ''SUMO1 modification of NF-kappaB2/p100 is essential for stimuli-induced p100 phosphorylation and processing.''; PubMedEurope PMCScholia
Liu Q, Li J, Khoury J, Colgan SP, Ibla JC.; ''Adenosine signaling mediates SUMO-1 modification of IkappaBalpha during hypoxia and reoxygenation.''; PubMedEurope PMCScholia
Liu X, Wang Q, Chen W, Wang C.; ''Dynamic regulation of innate immunity by ubiquitin and ubiquitin-like proteins.''; PubMedEurope PMCScholia
Renner F, Moreno R, Schmitz ML.; ''SUMOylation-dependent localization of IKKepsilon in PML nuclear bodies is essential for protection against DNA-damage-triggered cell death.''; PubMedEurope PMCScholia
Mabb AM, Wuerzberger-Davis SM, Miyamoto S.; ''PIASy mediates NEMO sumoylation and NF-kappaB activation in response to genotoxic stress.''; PubMedEurope PMCScholia
Liu Y, Bridges R, Wortham A, Kulesz-Martin M.; ''NF-κB repression by PIAS3 mediated RelA SUMOylation.''; PubMedEurope PMCScholia
NFKBIA (IKBA, IkappaBalpha) is SUMOylated at lysine-21 with SUMO1 (Desterro et al. 1998, Rodriguez et al. 2001, Liu et al. 2009). SUMOylation blocks ubiquitin-mediated proteolysis of NFKBIA and thereby inhibits NF-kappaB dependent transcription and acts as an anti-inflammatory. Adenosine signaling increases SUMOylation of NFKBIA with SUMO1. Nuclear import of NFKBIA is required for SUMOylation.
PIAS4 SUMOylates IKBKG with SUMO1 at lysine-277 and lysine-309 (Huang et al. 2003, Mabb et al. 2006). SUMOylation occurs in the nucleus when IKBKG is unbound to IKK. The interaction between PIAS4 and IKBKG is increased by genotoxic stress. SUMOylation is independent of ATM.
TOPORS SUMOylates phosphorylated IKBKE (IKKI, IKKE) with SUMO1 at lysine-231 (Renner et al. 2010). SUMOylation causes IKBKE to localize with PML in the nucleus and is required for IKBKE to trigger phosphorylation of NF-kappaB p65.
Unprocessed NFKB2 p100 is SUMOylated with SUMO1 at lysine-90, lysine-298, lysine-689, and lysine-863 (Vatsyayan et al. 2008). SUMOylation of p100 is required for phosphorylation of p100 prior to processing to yield p52. Blockage of SUMOylation consequently interferes with import of NFKB2 p52 into the nucleus.
PIAS3 SUMOylates RELA with SUMO3 at lysine-37, lysine-121, and lysine-122 (Liu et al. 2012, Hendriks et al. 2014). SUMOylation occurs when RELA is bound to NF-kB binding sites on DNA in the nucleus. SUMOylation represses transcriptional activity of RELA and is enhanced by NF-kB activation by TNFalpha.
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