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KMID : 0578320230460070430
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Molecules and Cells
2023 Volume.46 No. 7 p.430 ~ p.440
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TSG101 Physically Interacts with Linear Ubiquitin Chain Assembly Complex (LUBAC) and Upregulates the TNFα-Induced NF-κB Activation
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Kim Eun-Ju
Cho Hyun-Chu
Lee Ga-Eul
Baek Hea-Won
Lee In-Young
Choi Eui-Ju
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Abstract
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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.
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KEYWORD
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HOIL-1-interacting protein, linear ubiquitin chain assembly complex, nuclear factor-κB, tumor necrosis factor α, tumor susceptibility gene 101
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