Transcriptional activation of known and novel apoptotic pathways by Nur77 orphan steroid receptor.
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.
Rajpal
Arvind
A
Department of Molecular and Cell Biology, Division of Immunology and Cancer Research Laboratory, 469 LSA, University of California, Berkeley, CA 94720-3200, USA.
Cho
Yuri A
YA
Yelent
Biana
B
Koza-Taylor
Petra H
PH
Li
Dongling
D
Chen
Elaine
E
Whang
Michael
M
Kang
Chulho
C
Turi
Thomas G
TG
Winoto
Astar
A
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001483:Base Sequence; D002478:Cells, Cultured; D003001:Cloning, Molecular; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D004926:Escherichia coli / Q000166:cytology / Q000235:genetics / Q000502:physiology; D005260:Female; D005838:Genotype; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D020411:Oligonucleotide Array Sequence Analysis; D011247:Pregnancy; D051381:Rats; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D015533:Transcriptional Activation / Q000235:genetics*
D017931:DNA Primers; D004268:DNA-Binding Proteins; C539821:NR4A1 protein, human; C539818:Nr4a1 protein, mouse; C539820:Nr4a1 protein, rat; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D011948:Receptors, Antigen, T-Cell; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D014157:Transcription Factors