1. Academic Validation
  2. UXT-V1 protects cells against TNF-induced apoptosis through modulating complex II formation

UXT-V1 protects cells against TNF-induced apoptosis through modulating complex II formation

  • Mol Biol Cell. 2011 Apr 15;22(8):1389-97. doi: 10.1091/mbc.E10-10-0827.
Yuefeng Huang 1 Liang Chen Yi Zhou Heng Liu Jueqing Yang Zhenggang Liu Chen Wang
Affiliations

Affiliation

  • 1 Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Abstract

Proteins that directly regulate tumor necrosis factor (TNF) signaling have critical roles in determining cell death and survival. Previously we characterized ubiquitously expressed transcript (UXT)-V2 as a novel transcriptional cofactor to regulate nuclear factor-κB in the nucleus. Here we report that another splicing isoform of UXT, UXT-V1, localizes in cytoplasm and regulates TNF-induced Apoptosis. UXT-V1 knockdown cells are hypersensitive to TNF-induced Apoptosis. We demonstrated that UXT-V1 is a new component of TNF Receptor signaling complex. We found that UXT-V1 binds to TNF receptor-associated factor 2 and prevents TNF receptor-associated death domain protein from recruiting Fas-associated protein with death domain. More importantly, UXT-V1 is a short-half-life protein, the degradation of which facilitates the formation of the apoptotic receptor complex II in response to TNF treatment. This study demonstrates that UXT-V1 is a novel regulator of TNF-induced Apoptosis and sheds new light on the underlying molecular mechanism of this process.

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