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

• Published in: Molecules and cells Vol. 46; no. 7; pp. 430 - 440
• Main Authors: Kim, Eunju, Cho, Hyunchu, Lee, Gaeul, Baek, Heawon, Lee, In Young, Choi, Eui-Ju
• Format: Journal Article
• Language: English
• Published: United States Korean Society for Molecular and Cellular Biology 31.07.2023
• Subjects: Genes, Regulator; NF-kappa B; Signal Transduction; Tumor Necrosis Factor-alpha - pharmacology; Ubiquitins; nuclear factor-κB; tumor susceptibility gene 101; linear ubiquitin chain assembly complex; tumor necrosis factor α; HOIL-1-interacting protein
• ISSN: 1016-8478; 0219-1032
• DOI: 10.14348/molcells.2023.0026

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.