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

The EMBO journal | Mar 4, 2009

http://www.ncbi.nlm.nih.gov/pubmed/19131965

The RING domain protein RNF11 is overexpressed in breast cancers and promotes tumour growth factor-beta (TGF-beta) signalling. RNF11 has been proposed to regulate TGF-beta 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-kappaB 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-kappaB and JNK signalling. RNF11 interacted with the NF-kappaB 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-kappaB 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.

Pubmed ID: 19131965 RIS Download

Mesh terms: Carrier Proteins | Cell Line | DNA-Binding Proteins | Down-Regulation | Gene Knockdown Techniques | Humans | Intracellular Signaling Peptides and Proteins | JNK Mitogen-Activated Protein Kinases | Lipopolysaccharides | Monocytes | NF-kappa B | Neoplasm Proteins | Nuclear Pore Complex Proteins | Nuclear Proteins | Protein Binding | Protein Structure, Tertiary | RNA, Small Interfering | RNA-Binding Proteins | Signal Transduction | TNF Receptor-Associated Factor 6 | Transforming Growth Factor beta | Ubiquitin-Protein Ligases | Ubiquitination

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