TRAF6 Phosphorylation Prevents Its Autophagic Degradation and Re-Shapes LPS-Triggered Signaling Networks.
TRAF6 Phosphorylation Prevents Its Autophagic Degradation and Re-Shapes LPS-Triggered Signaling Networks.
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DOI：
10.3390/cancers13143618
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发表时间：
2021-07-19
期刊：
影响因子：
5.2
通讯作者：
Schmitz ML
中科院分区：
文献类型：
--
作者：
Busch J;Moreno R;de la Vega L;Saul VV;Bacher S;von Zweydorf F;Ueffing M;Weber A;Gloeckner CJ;Linne U;Kracht M;Schmitz ML
Here, we reveal that basal turnover and autophagy-induced decay of the ubiquitin E3 ligase TRAF6 is antagonized by IKKε-mediated phosphorylation at five serines. Phosphoproteomic experiments show that TRAF6 and its phosphorylation contribute to the remodeling of LPS- and autophagyinduced signaling networks, revealing an intricate link between inflammatory and metabolic processes that are frequently dysregulated in cancer. The ubiquitin E3 ligase TNF Receptor Associated Factor 6 (TRAF6) participates in a large number of different biological processes including innate immunity, differentiation and cell survival, raising the need to specify and shape the signaling output. Here, we identify a lipopolysaccharide (LPS)-dependent increase in TRAF6 association with the kinase IKKε (inhibitor of NF-κB kinase subunit ε) and IKKε-mediated TRAF6 phosphorylation at five residues. The reconstitution of TRAF6-deficient cells, with TRAF6 mutants representing phosphorylation-defective or phospho-mimetic TRAF6 variants, showed that the phospho-mimetic TRAF6 variant was largely protected from basal ubiquitin/proteasome-mediated degradation, and also from autophagy-mediated decay in autolysosomes induced by metabolic perturbation. In addition, phosphorylation of TRAF6 and its E3 ligase function differentially shape basal and LPS-triggered signaling networks, as revealed by phosphoproteome analysis. Changes in LPS-triggered phosphorylation networks of cells that had experienced autophagy are partially dependent on TRAF6 and its phosphorylation status, suggesting an involvement of this E3 ligase in the interplay between metabolic and inflammatory circuits.
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影响因子：
44.1
作者：
Hu H;Sun SC
通讯作者：
Sun SC
MAVS 通过 TRAF 以 NEMO 依赖和独立方式激活 TBK1 和 IKKε
影响因子：
6.7
作者：
Fang R;Jiang Q;Zhou X;Wang C;Guan Y;Tao J;Xi J;Feng JM;Jiang Z
通讯作者：
Jiang Z
DOI：
10.1038/nri.2016.100
发表时间：
2016-11
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
Cadwell K
通讯作者：
Cadwell K
影响因子：
16.6
作者：
Balic, Jesse J.;Albargy, Hassan;Mansell, Ashley
通讯作者：
Mansell, Ashley
影响因子：
5.6
作者：
Das, Anubrita;Middleton, Adam J.;Day, Catherine L.
通讯作者：
Day, Catherine L.