NF-κB repression by PIAS3 mediated ReLA SUMOylation

Yuangang Liu, Rebecca Bridges, Aaron Wortham, Molly Kulesz-Martin

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Negative regulation of the NF-κB transcription factor is essential for tissue homeostasis in response to stress and inflammation. NF-κB activity is regulated by a variety of biochemical mechanisms including phosphorylation, acetylation, and ubiquitination. In this study, we provide the first experimental evidence that NF-κB is regulated by SUMOylation, where the RelA subunit of NF-κB is SUMOylated by PIAS3, a member of the PIAS (protein inhibitor of activated STAT) protein family with E3 SUMO ligase activity. PIAS3-mediated NF-κB repression was compromised by either RelA mutant resistant to SUMOylation or PIAS3 mutant defective in SUMOylation. PIAS3-mediated SUMOylation of endogenous RelA was induced by NF-κB activation thus forming a negative regulatory loop. The SUMOylation of endogenous RelA was enhanced in IκBα null as compared with wild type fibroblasts. The RelA SUMOylation was induced by TNFα but not leptomycin B mediated RelA nuclear translocation. Furthermore, RelA mutants defective in DNA binding were not SUMOylated by PIAS3, suggesting that RelA DNA binding is a signal for PIAS3-mediated SUMOylation. These results support a novel negative feedback mechanism for NF-κB regulation by PIAS3-mediated RelA SUMOylation.

Original languageEnglish (US)
Article numbere37636
JournalPLoS One
Volume7
Issue number5
DOIs
StatePublished - May 23 2012

Fingerprint

Sumoylation
Protein Inhibitors of Activated STAT
Tissue homeostasis
Acetylation
mutants
Phosphorylation
DNA
Fibroblasts
Ligases
biochemical mechanisms
Transcription Factors
Chemical activation
acetylation
Feedback
ligases
fibroblasts
stress response
homeostasis
phosphorylation
transcription factors

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

NF-κB repression by PIAS3 mediated ReLA SUMOylation. / Liu, Yuangang; Bridges, Rebecca; Wortham, Aaron; Kulesz-Martin, Molly.

In: PLoS One, Vol. 7, No. 5, e37636, 23.05.2012.

Research output: Contribution to journalArticle

Liu, Yuangang ; Bridges, Rebecca ; Wortham, Aaron ; Kulesz-Martin, Molly. / NF-κB repression by PIAS3 mediated ReLA SUMOylation. In: PLoS One. 2012 ; Vol. 7, No. 5.
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