TR4 orphan nuclear receptor functions as an apoptosis modulator via regulation of Bcl-2 gene expression.
While Bcl-2 plays an important role in cell apoptosis, its relationship to the orphan nuclear receptors remains unclear. Here we report that mouse embryonic fibroblast (MEF) cells prepared from TR4-deficient (TR4(-/-)) mice are more susceptible to UV-irradiation mediated apoptosis compared to TR4-Wildtype (TR4(+/+)) littermates. Substantial increasing TR4(-/-) MEF apoptosis to UV-irradiation was correlated to the down-regulation of Bcl-2 RNA and protein expression and collaterally increased caspase-3 activity. Furthermore, this TR4-induced Bcl-2 gene expression can be suppressed by co-transfection with TR4 coregulators, such as androgen receptor (AR) and receptor-interacting protein 140 (RIP140) in a dose-dependent manner. Together, our results demonstrate that TR4 might function as an apoptosis modulator through induction of Bcl-2 gene expression.
Kim
Eungseok
E
George Whipple Lab for Cancer Research, Department of Pathology, University of Rochester Medical Center, Rochester, NY 14642, USA.
Ma
Wen-Lung
WL
Lin
Din-Lii
DL
Inui
Shigeki
S
Chen
Yuh-Ling
YL
Chang
Chawnshang
C
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000528:radiation effects; D019556:COS Cells; D002522:Chlorocebus aethiops; D015536:Down-Regulation / Q000235:genetics / Q000528:radiation effects; D005347:Fibroblasts / Q000378:metabolism / Q000528:radiation effects; D005786:Gene Expression Regulation / Q000528:radiation effects; D006801:Humans; D051379:Mice; D009687:Nuclear Proteins / Q000378:metabolism; D000078723:Nuclear Receptor Interacting Protein 1; D011401:Promoter Regions, Genetic / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics*; D011944:Receptors, Androgen / Q000378:metabolism; D011987:Receptors, Steroid / Q000235:genetics / Q000378:metabolism*; D011988:Receptors, Thyroid Hormone / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000528:radiation effects; D014466:Ultraviolet Rays
D048868:Adaptor Proteins, Signal Transducing; C000627127:NRIP1 protein, human; C490514:Nr2c2 protein, mouse; D009687:Nuclear Proteins; D000078723:Nuclear Receptor Interacting Protein 1; D019253:Proto-Oncogene Proteins c-bcl-2; D011944:Receptors, Androgen; D011987:Receptors, Steroid; D011988:Receptors, Thyroid Hormone