TY - JOUR
T1 - TR4 orphan nuclear receptor functions as an apoptosis modulator via regulation of Bcl-2 gene expression
AU - Kim, Eungseok
AU - Ma, Wen Lung
AU - Lin, Din Lii
AU - Inui, Shigeki
AU - Chen, Yuh Ling
AU - Chang, Chawnshang
N1 - Funding Information:
We thank Drs. M. Parker, R.H. Goodman, and J.C. Reed for kindly providing plasmids. This work was supported by the National Institutes of Health Grant and the George Whipple Professorship Endowment. The TR4 − / − mice were generated in collaboration with Lexicon Genetics, Inc. We also thank K. Wolf for help in manuscript preparation.
PY - 2007/9/21
Y1 - 2007/9/21
N2 - 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.
AB - 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.
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U2 - 10.1016/j.bbrc.2007.06.168
DO - 10.1016/j.bbrc.2007.06.168
M3 - Article
C2 - 17655826
AN - SCOPUS:34547497908
SN - 0006-291X
VL - 361
SP - 323
EP - 328
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 2
ER -