Roy, M;
Singh, K;
Shinde, A;
Singh, J;
Mane, M;
Bedekar, S;
Tailor, Y;
... Singh, R; + view all
(2022)
TNF-α-induced E3 ligase, TRIM15 inhibits TNF-α-regulated NF-κB pathway by promoting turnover of K63 linked ubiquitination of TAK1.
Cellular Signalling
, 91
, Article 110210. 10.1016/j.cellsig.2021.110210.
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Abstract
Ubiquitin E3-ligases are recruited at different steps of TNF-α-induced NF-κB activation; however, their role in temporal regulation of the pathway remains elusive. The study systematically identified TRIMs as potential feedback regulators of the TNF-α-induced NF-κB pathway. We further observed that TRIM15 is “late” response TNF-α-induced gene and inhibits the TNF-α-induced NF-κB pathway in several human cell lines. TRIM15 promotes turnover of K63-linked ubiquitin chains in a PRY/SPRY domain-dependent manner. TRIM15 interacts with TAK1 and inhibits its K63-linked ubiquitination, thus NF-κB activity. Further, TRIM15 interacts with TRIM8 and inhibits cytosolic translocation to antagonize TRIM8 modualted NF-κB. TRIM8 and TRIM15 also show functionally inverse correlation in psoriasis condition. In conclusion, TRIM15 is TNF-α-induced late response gene and inhibits TNF-α induced NF-κB pathway hence a feedback modulator to keep the proinflammatory NF-κB pathway under control.
| Type: | Article |
|---|---|
| Title: | TNF-α-induced E3 ligase, TRIM15 inhibits TNF-α-regulated NF-κB pathway by promoting turnover of K63 linked ubiquitination of TAK1 |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.cellsig.2021.110210 |
| Publisher version: | https://doi.org/10.1016/j.cellsig.2021.110210 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | TNF-α, NF-κB, TRIM15, TRIM8, Ubiquitination, Functional antagonism |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Cell and Developmental Biology |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10166414 |
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