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Transcriptional activation of known and novel apoptotic pathways by Nur77 orphan steroid receptor
Author(s) -
Rajpal Arvind,
Cho Yuri A.,
Yelent Biana,
KozaTaylor Petra H.,
Li Dongling,
Chen Elaine,
Whang Michael,
Kang Chulho,
Turi Thomas G.,
Winoto Astar
Publication year - 2003
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/cdg620
Subject(s) - nerve growth factor ib , biology , microbiology and biotechnology , apoptosis , orphan receptor , neuron derived orphan receptor 1 , nuclear receptor , transcription factor , mitochondrion , gene , genetics
Nur77 is a nuclear orphan steroid receptor that has been implicated in negative selection. Expression of Nur77 in thymocytes and cell lines leads to apoptosis through a mechanism that remains unclear. In some cell lines, Nur77 was reported to act through a transcription‐independent mechanism involving translocation to mitochondria, leading to cytochrome c release. However, we show here that Nur77‐mediated apoptosis in thymocytes does not involve cytoplasmic cytochrome c release and cannot be rescued by Bcl‐2. Microarray analysis shows that Nur77 induces many genes, including two novel genes (NDG1, NDG2) and known apoptotic genes FasL and TRAIL. Characterization of NDG1 and NDG2 indicates that NDG1 initiates a novel apoptotic pathway in a Bcl‐2‐independent manner. Thus Nur77‐mediated apoptosis in T cells involves Bcl‐2 independent transcriptional activation of several known and novel apoptotic pathways.