TSG101 Physically Interacts with Linear Ubiquitin Chain Assembly Complex (LUBAC) and Upregulates the TNFα-Induced NF-κB Activation

Overview

Journal Mol Cells

Publisher Elsevier

Specialties Cell Biology
Molecular Biology

Date 2023 Jul 11

PMID 37431163

Authors

Eunju Kim

Hyunchu Cho

Gaeul Lee

Heawon Baek

In Young Lee

Eui-Ju Choi

Affiliations

Soon will be listed here.

Abstract

Linear ubiquitin chain assembly complex (LUBAC) is a ubiquitin E3 ligase complex composed of HOIP, HOIL-1L, and SHARPIN that catalyzes the formation of linear/M1- linked ubiquitin chain. It has been shown to play a pivotal role in the nuclear factor (NF)-κB signaling induced by proinflammatory stimuli. Here, we found that tumor susceptibility gene (TSG101) physically interacts with HOIP, a catalytic component of LUBAC, and potentiates LUBAC activity. Depletion of TSG101 expression by RNA interference decreased TNFα-induced linear ubiquitination and the formation of TNFα receptor 1 signaling complex (TNFRSC). Furthermore, TSG101 facilitated the TNFα-induced stimulation of the NF-κB pathway. Thus, we suggest that TSG101 functions as a positive modulator of HOIP that mediates TNFα-induced NF-κB signaling pathway.

Citing Articles

Tsg101 mimicry of canonical E2 enzymes underlies its role in ubiquitin signaling.

Nyenhuis D, Watanabe S, Tjandra N, Carter C Proc Natl Acad Sci U S A. 2024; 122(1):e2419542121.

PMID: 39739800 PMC: 11725782. DOI: 10.1073/pnas.2419542121.

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