Cytochrome c release and apoptosis induced by mitochondrial targeting of nuclear orphan receptor TR3.
TR3, an immediate-early response gene and an orphan member of the steroid-thyroid hormone-retinoid receptor superfamily of transcription factors, regulates apoptosis through an unknown mechanism. In response to apoptotic stimuli, TR3 translocates from the nucleus to mitochondria to induce cytochrome c release and apoptosis. Mitochondrial targeting of TR3, but not its DNA binding and transactivation, is essential for its proapoptotic effect. Our results reveal a mechanism by which a nuclear transcription factor translocates to mitochondria to initiate apoptosis.
Li
H
H
The Burnham Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.
Kolluri
S K
SK
Gu
J
J
Dawson
M I
MI
Cao
X
X
Hobbs
P D
PD
Lin
B
B
Chen
G
G
Lu
J
J
Lin
F
F
Xie
Z
Z
Fontana
J A
JA
Reed
J C
JC
Zhang
X
X
D017209:Apoptosis; D002458:Cell Fractionation; D002467:Cell Nucleus / Q000378:metabolism; D003574:Cytochrome c Group / Q000378:metabolism*; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology; D017930:Genes, Reporter; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism / Q000502:physiology; D008928:Mitochondria / Q000378:metabolism*; D009154:Mutation; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D017434:Protein Structure, Tertiary; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation; D014162:Transfection; D014407:Tumor Cells, Cultured
D003574:Cytochrome c Group; D004268:DNA-Binding Proteins; D005231:Fatty Acids, Unsaturated; C539821:NR4A1 protein, human; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D004247:DNA; C038753:leptomycin B