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

  • Eunju Kim (Laboratory of Cell Death and Human Diseases, Department of Life Sciences, Korea University) ;
  • Hyunchu Cho (Laboratory of Cell Death and Human Diseases, Department of Life Sciences, Korea University) ;
  • Gaeul Lee (Laboratory of Cell Death and Human Diseases, Department of Life Sciences, Korea University) ;
  • Heawon Baek (Laboratory of Cell Death and Human Diseases, Department of Life Sciences, Korea University) ;
  • In Young Lee (Laboratory of Cell Death and Human Diseases, Department of Life Sciences, Korea University) ;
  • Eui-Ju Choi (Laboratory of Cell Death and Human Diseases, Department of Life Sciences, Korea University)
  • 투고 : 2023.02.01
  • 심사 : 2023.03.26
  • 발행 : 2023.07.31

초록

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 (TNF-RSC). 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.

키워드

과제정보

We thank K. Iwai for GST-TNFα cDNA. This work was supported by a Korea University grant (E.-J.C.).

참고문헌

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