First Author | Huang Y | Year | 2011 |
Journal | Mol Biol Cell | Volume | 22 |
Issue | 8 | Pages | 1389-97 |
PubMed ID | 21307340 | Mgi Jnum | J:183001 |
Mgi Id | MGI:5317281 | Doi | 10.1091/mbc.E10-10-0827 |
Citation | Huang Y, et al. (2011) UXT-V1 protects cells against TNF-induced apoptosis through modulating complex II formation. Mol Biol Cell 22(8):1389-97 |
abstractText | 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-kappaB 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. |