The ubiquitin-editing enzyme A20 requires RNF11 to downregulate NF-κB signalling

Noula Shembade, Kislay Parvatiyar, Nicole S. Harhaj, Edward W. Harhaj

Research output: Contribution to journalArticle

Abstract

The RING domain protein RNF11 is overexpressed in breast cancers and promotes tumour growth factor-beta (TGF-β) signalling. RNF11 has been proposed to regulate TGF-β signalling by interacting with HECT- and SCF-type E3 ligases; however, the role of RNF11 in other signalling pathways is poorly understood. Here, we demonstrate a novel function of RNF11 as a negative regulator of NF-κB and jun N-terminal kinase (JNK) signalling pathways. Knockdown of RNF11 with siRNA resulted in persistent tumour necrosis factor (TNF)- and lipopolysaccharide (LPS)-mediated NF-κB and JNK signalling. RNF11 interacted with the NF-κB inhibitor A20 and its regulatory protein TAX1BP1 in a stimulus-dependent manner. RNF11 negatively regulated RIP1 and TRAF6 ubiquitination upon stimulation with TNF and LPS, respectively. Furthermore, RNF11 was required for A20 to interact with and inactivate RIP1 to inhibit TNF-mediated NF-κB activation. Our studies reveal that RNF11, together with TAX1BP1 and Itch, is an essential component of an A20 ubiquitin-editing protein complex that ensures transient activation of inflammatory signalling pathways.

Original languageEnglish (US)
Pages (from-to)513-522
Number of pages10
JournalThe EMBO journal
Volume28
Issue number5
DOIs
StatePublished - Mar 4 2009
Externally publishedYes

Fingerprint

Ubiquitin
Down-Regulation
Tumor Necrosis Factor-alpha
Lipopolysaccharides
Intercellular Signaling Peptides and Proteins
Phosphotransferases
Enzymes
TNF Receptor-Associated Factor 6
Ubiquitin-Protein Ligases
Ubiquitination
Small Interfering RNA
Tumors
Neoplasms
Proteins
Chemical activation
Breast Neoplasms
nuclear factor-jun

Keywords

  • A20
  • Itch
  • NF-κB
  • RNF11
  • TAX1BP1

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Neuroscience(all)

Cite this

The ubiquitin-editing enzyme A20 requires RNF11 to downregulate NF-κB signalling. / Shembade, Noula; Parvatiyar, Kislay; Harhaj, Nicole S.; Harhaj, Edward W.

In: The EMBO journal, Vol. 28, No. 5, 04.03.2009, p. 513-522.

Research output: Contribution to journalArticle

Shembade, N, Parvatiyar, K, Harhaj, NS & Harhaj, EW 2009, 'The ubiquitin-editing enzyme A20 requires RNF11 to downregulate NF-κB signalling', The EMBO journal, vol. 28, no. 5, pp. 513-522. https://doi.org/10.1038/emboj.2008.285
Shembade, Noula ; Parvatiyar, Kislay ; Harhaj, Nicole S. ; Harhaj, Edward W. / The ubiquitin-editing enzyme A20 requires RNF11 to downregulate NF-κB signalling. In: The EMBO journal. 2009 ; Vol. 28, No. 5. pp. 513-522.
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