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Publication : Nur77 as a survival factor in tumor necrosis factor signaling.

First Author  Suzuki S Year  2003
Journal  Proc Natl Acad Sci U S A Volume  100
Issue  14 Pages  8276-80
PubMed ID  12815108 Mgi Jnum  J:84428
Mgi Id  MGI:2667579 Doi  10.1073/pnas.0932598100
Citation  Suzuki S, et al. (2003) Nur77 as a survival factor in tumor necrosis factor signaling. Proc Natl Acad Sci U S A 100(14):8276-80
abstractText  The immediate-early gene Nur77, which encodes an orphan nuclear receptor, is rapidly induced by various stress stimuli, including tumor necrosis factor (TNF). Nur77 has been implicated in mediating apoptosis, particularly in T cells and tumor cells. We report here that Nur77 can play a role in antagonizing apoptosis in TNF signaling. Nur77 expression is strongly induced by TNF. Interestingly, unlike most antiapoptotic molecules, this induced expression of Nur77 is largely independent of NF-kappa B. Ectopic expression of Nur77 can protect wild-type, TRAF2-/-, and RelA-/- cells from apoptosis induced by TNF, whereas expression of a dominant-negative form of Nur77 (DN-Nur77) accelerates TNF-mediated cell death in the mutant cells. In mouse embryonic fibroblasts, Nur77 remains in the nucleus in response to TNF and is not translocated to the mitochondria, where it was reported to mediate apoptosis. Our results suggest that Nur77 is a survival effector protein in the context of TNF-mediated signaling.
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