Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
GoGreen Membership

Site Tools

  • AAAS
  • Subscribe
  • Feedback

Site Search

Search Advanced

Logo for

Mol. Cell. Biol. 20 (3): 957-970

Copyright © 2000 by the American Society for Microbiology. All rights reserved.

Molecular and Cellular Biology, February 2000, p. 957-970, Vol. 20, No. 3
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Orphan Receptor COUP-TF Is Required for Induction of Retinoic Acid Receptor beta , Growth Inhibition, and Apoptosis by Retinoic Acid in Cancer Cells

Bingzhen Lin, Guo-quan Chen, Dongmei Xiao, Siva Kumar Kolluri, Xihua Cao, Hong Su, and Xiao-kun Zhang*

Cancer Research Center, The Burnham Institute, La Jolla, California 92037

Received 31 August 1999/Returned for modification 1 October 1999/Accepted 5 November 1999

Retinoic acid receptor beta  (RARbeta ) plays a critical role in mediating the anticancer effects of retinoids. Expression of RARbeta is highly induced by retinoic acid (RA) through a RA response element (beta RARE) that is activated by heterodimers of RARs and retinoid X receptors (RXRs). However, RARbeta induction is often lost in cancer cells despite expression of RARs and RXRs. In this study, we provide evidence that orphan receptor COUP-TF is required for induction of RARbeta expression, growth inhibition, and apoptosis by RA in cancer cells. Expression of COUP-TF correlates with RARbeta induction in a variety of cancer cell lines. In addition, stable expression of COUP-TF in COUP-TF-negative cancer cells restores induction of RARbeta expression, growth inhibition, and apoptosis by RA, whereas inhibition of COUP-TF by expression of COUP-TF antisense RNA represses the RA effects. In a transient transfection assay, COUP-TF strongly induced transcriptional activity of the RARbeta promoter in a RA- and RARalpha -dependent manner. By mutation analysis, we demonstrate that the effect of COUP-TF requires its binding to a DR-8 element present in the RARbeta promoter. The binding of COUP-TF to the DR-8 element synergistically increases the RA-dependent RARalpha transactivation function by enhancing the interaction of RARalpha with its coactivator CREB binding protein. These results demonstrate that COUP-TF, by serving as an accessory protein for RARalpha to induce RARbeta expression, plays a critical role in regulating the anticancer activities of retinoids.

* Corresponding author. Mailing address: The Burnham Institute, Cancer Research Center, 10901 N. Torrey Pines Rd., La Jolla, CA 92037. Phone: (858) 646-3141. Fax: (858) 646-3195. E-mail: xzhang{at}burnham-inst.org.

Molecular and Cellular Biology, February 2000, p. 957-970, Vol. 20, No. 3
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Comparative genomics identifies genes mediating cardiotoxicity in the embryonic zebrafish heart.
J. Chen, S. A. Carney, R. E. Peterson, and W. Heideman (2008)
Physiol Genomics 33, 148-158
   Abstract »    Full Text »    PDF »
Decreased Chicken Ovalbumin Upstream Promoter Transcription Factor II Expression in Tamoxifen-Resistant Breast Cancer Cells..
K. A. Riggs, N. S. Wickramasinghe, R. K. Cochrum, M. B. Watts, and C. M. Klinge (2006)
Cancer Res. 66, 10188-10198
   Abstract »    Full Text »    PDF »
Increased Retinoic Acid Receptor-{beta}4 Correlates In vivo with Reduced Retinoic Acid Receptor-{beta}2 in Esophageal Squamous Cell Carcinoma.
X.-c. Xu, J. J. Lee, T.-T. Wu, A. Hoque, J. A. Ajani, and S. M. Lippman (2005)
Cancer Epidemiol. Biomarkers Prev. 14, 826-829
   Abstract »    Full Text »    PDF »
Valproic acid, in combination with all-trans retinoic acid and 5-aza-2'-deoxycytidine, restores expression of silenced RAR{beta}2 in breast cancer cells.
N. P. Mongan and L. J. Gudas (2005)
Mol. Cancer Ther. 4, 477-486
   Abstract »    Full Text »    PDF »
c-Jun N-Terminal Kinase Contributes to Aberrant Retinoid Signaling in Lung Cancer Cells by Phosphorylating and Inducing Proteasomal Degradation of Retinoic Acid Receptor {alpha}.
H. Srinivas, D. M. Juroske, S. Kalyankrishna, D. D. Cody, R. E. Price, X.-C. Xu, R. Narayanan, N. L. Weigel, and J. M. Kurie (2005)
Mol. Cell. Biol. 25, 1054-1069
   Abstract »    Full Text »    PDF »
Retinoid X Receptor Regulates Nur77/Thyroid Hormone Receptor 3-Dependent Apoptosis by Modulating Its Nuclear Export and Mitochondrial Targeting.
X. Cao, W. Liu, F. Lin, H. Li, S. K. Kolluri, B. Lin, Y.-h. Han, M. I. Dawson, and X.-k. Zhang (2004)
Mol. Cell. Biol. 24, 9705-9725
   Abstract »    Full Text »    PDF »
Expression of Chicken Ovalbumin Upstream Promoter-Transcription Factor II Enhances Invasiveness of Human Lung Carcinoma Cells.
R. Navab, J. M. Gonzalez-Santos, M. R. Johnston, J. Liu, P. Brodt, M.-S. Tsao, and J. Hu (2004)
Cancer Res. 64, 5097-5105
   Abstract »    Full Text »    PDF »
A Novel Retinoic Acid-Responsive Element Regulates Retinoic Acid-Induced BLR1 Expression.
J. Wang and A. Yen (2004)
Mol. Cell. Biol. 24, 2423-2443
   Abstract »    Full Text »    PDF »
Mitogenic Effect of Orphan Receptor TR3 and Its Regulation by MEKK1 in Lung Cancer Cells.
S. K. Kolluri, N. Bruey-Sedano, X. Cao, B. Lin, F. Lin, Y.-H. Han, M. I. Dawson, and X.-k. Zhang (2003)
Mol. Cell. Biol. 23, 8651-8667
   Abstract »    Full Text »    PDF »
Regulation of Retinoic Acid Receptor {beta} Expression by Peroxisome Proliferator-activated Receptor {gamma} Ligands in Cancer Cells.
S. Y. James, F. Lin, S. K. Kolluri, M. I. Dawson, and X.-k. Zhang (2003)
Cancer Res. 63, 3531-3538
   Abstract »    Full Text »    PDF »
A Complex Deoxyribonucleic Acid Response Element in the Rat Ca2+/Calmodulin-Dependent Protein Kinase IV Gene 5'-Flanking Region Mediates Thyroid Hormone Induction and Chicken Ovalbumin Upstream Promoter Transcription Factor 1 Repression.
Y.-Y. Liu and G. A. Brent (2002)
Mol. Endocrinol. 16, 2439-2451
   Abstract »    Full Text »    PDF »
Regulation of Human Clara Cell 10 kD Protein Expression by Chicken Ovalbumin Upstream Promoter Transcription Factors (COUP-TFs).
R. Navab, Y. Wang, Y.-H. Chow, A. Wang, R. P. Jankov, N. Takamoto, S. Y. Tsai, M.-J. Tsai, A. K. Tanswell, and J. Hu (2002)
Am. J. Respir. Cell Mol. Biol. 27, 273-285
   Abstract »    Full Text »    PDF »
Mutational Analysis of Human Thioredoxin Reductase 1. EFFECTS ON p53-MEDIATED GENE EXPRESSION AND INTERFERON AND RETINOIC ACID-INDUCED CELL DEATH.
X. Ma, J. Hu, D. J. Lindner, and D. V. Kalvakolanu (2002)
J. Biol. Chem. 277, 22460-22468
   Abstract »    Full Text »    PDF »
Regulation of Retinoic Acid-induced Inhibition of AP-1 Activity by Orphan Receptor Chicken Ovalbumin Upstream Promoter-Transcription Factor.
F. Lin, S. K. Kolluri, G.-q. Chen, and X.-k. Zhang (2002)
J. Biol. Chem. 277, 21414-21422
   Abstract »    Full Text »    PDF »
Multiple Phosphorylation Events Control Chicken Ovalbumin Upstream Promoter Transcription Factor I Orphan Nuclear Receptor Activity.
F. Gay, P. Barath, C. Desbois-Le Peron, R. Metivier, R. Le Guevel, D. Birse, and G. Salbert (2002)
Mol. Endocrinol. 16, 1332-1351
   Abstract »    Full Text »    PDF »
Retinoic Acid Upregulates Cone Arrestin Expression in Retinoblastoma Cells through a Cis Element in the Distal Promoter Region.
A. Li, X. Zhu, and C. M. Craft (2002)
Invest. Ophthalmol. Vis. Sci. 43, 1375-1383
   Abstract »    Full Text »    PDF »
Apoptosis Induction in Cancer Cells by a Novel Analogue of 6-[3-(1-Adamantyl)-4-hydroxyphenyl]-2-naphthalenecarboxylic Acid Lacking Retinoid Receptor Transcriptional Activation Activity.
M. I. Dawson, P. D. Hobbs, V. J. Peterson, M. Leid, C. W. Lange, K.-C. Feng, G.-q. Chen, J. Gu, H. Li, S. K. Kolluri, et al. (2001)
Cancer Res. 61, 4723-4730
   Abstract »    Full Text »    PDF »
Retinoic acid up-regulates myeloid ICAM-3 expression and function in a cell-specific fashion--evidence for retinoid signaling pathways in the mast cell lineage.
M. Babina, K. Mammeri, and B. M. Henz (2001)
J. Leukoc. Biol. 69, 361-372
   Abstract »    Full Text »
Speaker Abstracts.
(2001)
J. Nutr. 131, 186S-190
   Full Text »
Cell-Type-Specific Regulation of the Retinoic Acid Receptor Mediated by the Orphan Nuclear Receptor TLX.
M. Kobayashi, R. T. Yu, K. Yasuda, and K. Umesono (2000)
Mol. Cell. Biol. 20, 8731-8739
   Abstract »    Full Text »

ADVERTISEMENT
Click Me!

ADVERTISEMENT
Click Me!

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (pre-2008: Science's STKE. ISSN 1525-8882)