TR4 orphan nuclear receptor functions as an apoptosis modulator via regulation of Bcl-2 gene expression
- George Whipple Lab for Cancer Research, Departments of Pathology, Urology and Radiation Oncology, and The Cancer Center, University of Rochester Medical Center, Rochester, NY 14642 (United States)
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{sup -} {sup /-}) mice are more susceptible to UV-irradiation mediated apoptosis compared to TR4-Wildtype (TR4 {sup +/+}) littermates. Substantial increasing TR4{sup -} {sup /-} 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.
- OSTI ID:
- 20991539
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 361, Issue 2; Other Information: DOI: 10.1016/j.bbrc.2007.06.168; PII: S0006-291X(07)01432-5; Copyright (c) 2007 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
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