The E3 ubiquitin ligase RNF121 is a positive regulator of NF-κB activation

Cell Communication and Signaling

Short Report

Aimé Vazquez¹  Marie Pourcelot¹  Damien Arnoult¹  Neslihan Dogan¹  Naima Zemirli¹ 

[1] INSERM, UMR_S 1014, Hôpital Paul Brousse, 94800, Villejuif, France;Université Paris-Sud P11, 91400, Orsay, France;Equipe Labellisée Ligue contre le Cancer, 94800, Villejuif, France;

关键词: NF-κB;    Ubiquitination;    E3 ubiquitin ligase;    Golgi apparatus;    Innate immunity;   

DOI  :  10.1186/s12964-014-0072-8

 received in 2014-05-13, accepted in 2014-10-21,  发布年份 2014

来源: Springer

【 摘 要 】

BackgroundThe nuclear factor κB (NF-κB) family members regulate several biological processes as cell proliferation and differentiation, inflammation, immunity and tumor progression. Ubiquitination plays a key role in NF-κB activation and the ubiquitylated transmitters of the NF-κB signaling cascade accumulate in close proximity to endomembranes.FindingsWe performed an unbiased siRNA library screen targeting the 46 E3 ubiquitin ligases bearing transmembrane domains to uncover new modulators of NF-κB activation, using tumor necrosis factor–α (TNF-α) receptor (TNFR) stimulation as a model. We report here the identification of a new Golgi Apparatus-resident protein, RNF121, as an enhancer of NF-κB promoter activity through the catalytic function of its RING domain. From a molecular standpoint, while knocking down RNF121 did not alter RIP1 ubiquitination and IKK activation, the proteasomal degradation of IκBα was impaired suggesting that this E3 ubiquitin ligase regulates this process. However, RNF121 did not directly ubiquitinate IκBα While they were found in the same complex. Finally, we discovered that RNF121 acts as a broad regulator of NF-κB signaling since its silencing also dampens NF-κB activation following stimulation of Toll-Like Receptors (TLRs), Nod-Like Receptors (NLRs), RIG-I-Like Receptors (RLRs) or after DNA damages.ConclusionsThese results unveil an unexpected role of Golgi Apparatus and reveal RNF121 as a new player involved in the signaling leading to NF-κB activation.

【 授权许可】

Unknown   
© Zemirli et al.; licensee BioMed Central Ltd. 2014. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.