Abstract
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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing / metabolism
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Animals
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Apoptosis* / radiation effects
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COS Cells
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Chlorocebus aethiops
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Down-Regulation / genetics
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Down-Regulation / radiation effects
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Fibroblasts / metabolism
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Fibroblasts / radiation effects
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Gene Expression Regulation* / radiation effects
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Humans
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Mice
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Nuclear Proteins / metabolism
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Nuclear Receptor Interacting Protein 1
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Promoter Regions, Genetic / genetics
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Proto-Oncogene Proteins c-bcl-2 / genetics*
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Receptors, Androgen / metabolism
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Receptors, Steroid / genetics
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Receptors, Steroid / metabolism*
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Receptors, Thyroid Hormone / genetics
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Receptors, Thyroid Hormone / metabolism*
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Transcription, Genetic / radiation effects
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Ultraviolet Rays
Substances
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Adaptor Proteins, Signal Transducing
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NRIP1 protein, human
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Nr2c2 protein, mouse
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Nuclear Proteins
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Nuclear Receptor Interacting Protein 1
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Proto-Oncogene Proteins c-bcl-2
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Receptors, Androgen
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Receptors, Steroid
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Receptors, Thyroid Hormone