| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Tumor Biology |
at Serine 260 Impairs Its Metabolism and Function in Human Hepatocellular Carcinoma1
First Department of Internal Medicine, Gifu University School of Medicine, Gifu 500-8705, Japan [R. M-N., M. O., S. A., T. S., K. A., H. M.]; Division of Liver Diseases, Mount Sinai Medical Center, New York, New York 10029-6574 [S. L. F.]; and Laboratory of Molecular Cell Sciences, Tsukuba Institute, RIKEN, Tsukuba 305-0074, Japan [S. K.]
Retinoids induce apoptosis and differentiation of hepatocellular carcinoma (HCC) cells and are used clinically in the chemoprevention of HCC. We have shown previously that hepatocarcinogenesis is accompanied by accumulation of full-length retinoid X receptor 
(RXR), although the underlying mechanisms and biological implications have remained unclear. The present studies were based on the finding that the accumulated full-length RXR was phosphorylated at serine/threonine residues both in all human HCC tissues examined and in human HCC-derived HuH7 cells. Phosphorylation at serine 260 of RXR, a consensus site of mitogen-activated protein kinase, was closely linked to its retarded degradation, low transactivating activity, and the promotion of cancer cell growth. There was no genomic mutation in the RXR gene, and abrogation of phosphorylation by mitogen-activated protein kinase-specific inhibitors restored the degradation of RXR in an RXR ligand-dependent manner. These results suggest that phosphorylation of RXR may interfere with its metabolism and signaling in human HCC, which could lead to growth promotion of these tumors.
This article has been cited by other articles:
|
|
 |
|
  R. Matsushima-Nishiwaki, S. Takai, S. Adachi, C. Minamitani, E. Yasuda, T. Noda, K. Kato, H. Toyoda, Y. Kaneoka, A. Yamaguchi, et al. Phosphorylated Heat Shock Protein 27 Represses Growth of Hepatocellular Carcinoma via Inhibition of Extracellular Signal-regulated Kinase J. Biol. Chem., July 4, 2008; 283(27): 18852 - 18860. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Tatebe, M. Shimizu, Y. Shirakami, H. Tsurumi, and H. Moriwaki Synergistic Growth Inhibition by 9-cis-Retinoic Acid Plus Trastuzumab in Human Hepatocellular Carcinoma Cells Clin. Cancer Res., May 1, 2008; 14(9): 2806 - 2812. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Macoritto, L. Nguyen-Yamamoto, D. C. Huang, S. Samuel, X. F. Yang, T. T. Wang, J. H. White, and R. Kremer Phosphorylation of the Human Retinoid X Receptor {alpha} at Serine 260 Impairs Coactivator(s) Recruitment and Induces Hormone Resistance to Multiple Ligands J. Biol. Chem., February 22, 2008; 283(8): 4943 - 4956. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Grenier, F. S. Maupas, J.-F. Beaulieu, E. Seidman, E. Delvin, A. Sane, E. Tremblay, C. Garofalo, and E. Levy Effect of retinoic acid on cell proliferation and differentiation as well as on lipid synthesis, lipoprotein secretion, and apolipoprotein biogenesis Am J Physiol Gastrointest Liver Physiol, December 1, 2007; 293(6): G1178 - G1189. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Yamazaki, M. Shimizu, M. Okuno, R. Matsushima-Nishiwaki, N. Kanemura, H. Araki, H. Tsurumi, S. Kojima, I B. Weinstein, and H. Moriwaki Synergistic effects of RXR{alpha} and PPAR{gamma} ligands to inhibit growth in human colon cancer cells phosphorylated RXR{alpha} is a critical target for colon cancer management Gut, November 1, 2007; 56(11): 1557 - 1563. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Sun, V. Montana, K. Chellappa, Y. Brelivet, D. Moras, Y. Maeda, V. Parpura, B. M. Paschal, and F. M. Sladek Phosphorylation of a Conserved Serine in the Deoxyribonucleic Acid Binding Domain of Nuclear Receptors Alters Intracellular Localization Mol. Endocrinol., June 1, 2007; 21(6): 1297 - 1311. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Lattuada, P. Vigano, S. Mangioni, J. Sassone, S. Di Francesco, M. Vignali, and A. M. Di Blasio Accumulation of Retinoid X Receptor-{alpha} in Uterine Leiomyomas Is Associated with a Delayed Ligand-Dependent Proteasome-Mediated Degradation and an Alteration of Its Transcriptional Activity Mol. Endocrinol., March 1, 2007; 21(3): 602 - 612. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. L. Zimmerman, S. Thevananther, R. Ghose, A. R. Burns, and S. J. Karpen Nuclear Export of Retinoid X Receptor {alpha} in Response to Interleukin-1beta-mediated Cell Signaling: ROLES FOR JNK AND SER260 J. Biol. Chem., June 2, 2006; 281(22): 15434 - 15440. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. K. Kolluri, M. Corr, S. Y. James, M. Bernasconi, D. Lu, W. Liu, H. B. Cottam, L. M. Leoni, D. A. Carson, and X.-k. Zhang The R-enantiomer of the nonsteroidal antiinflammatory drug etodolac binds retinoid X receptor and induces tumor-selective apoptosis PNAS, February 15, 2005; 102(7): 2525 - 2530. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Takiyama, N. Miyokawa, A. Sugawara, S. Kato, K. Ito, K. Sato, K. Oikawa, H. Kobayashi, S. Kimura, and M. Tateno Decreased Expression of Retinoid X Receptor Isoforms in Human Thyroid Carcinomas J. Clin. Endocrinol. Metab., November 1, 2004; 89(11): 5851 - 5861. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Shimizu, M. Suzui, A. Deguchi, J. T. E. Lim, D. Xiao, J. H. Hayes, K. P. Papadopoulos, and I. B. Weinstein Synergistic Effects of Acyclic Retinoid and OSI-461 on Growth Inhibition and Gene Expression in Human Hepatoma Cells Clin. Cancer Res., October 1, 2004; 10(19): 6710 - 6721. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Takano, S. Adachi, M. Okuno, Y. Muto, T. Yoshioka, R. Matsushima-Nishiwaki, H. Tsurumi, K. Ito, S. L. Friedman, H. Moriwaki, et al. The RING Finger Protein, RNF8, Interacts with Retinoid X Receptor {alpha} and Enhances Its Transcription-stimulating Activity J. Biol. Chem., April 30, 2004; 279(18): 18926 - 18934. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Matsushima-Nishiwaki, M. Okuno, Y. Takano, S. Kojima, S. L. Friedman, and H. Moriwaki Molecular mechanism for growth suppression of human hepatocellular carcinoma cells by acyclic retinoid Carcinogenesis, August 1, 2003; 24(8): 1353 - 1359. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Rome, K. Clement, R. Rabasa-Lhoret, E. Loizon, C. Poitou, G. S. Barsh, J.-P. Riou, M. Laville, and H. Vidal Microarray Profiling of Human Skeletal Muscle Reveals That Insulin Regulates ~800 Genes during a Hyperinsulinemic Clamp J. Biol. Chem., May 9, 2003; 278(20): 18063 - 18068. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. C. Ross Retinoid Production and Catabolism: Role of Diet in Regulating Retinol Esterification and Retinoic Acid Oxidation J. Nutr., January 1, 2003; 133(1): 291S - 296. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Osawa, M. Nagaki, Y. Banno, D. A. Brenner, T. Asano, Y. Nozawa, H. Moriwaki, and S. Nakashima Tumor Necrosis Factor Alpha-Induced Interleukin-8 Production via NF-{kappa}B and Phosphatidylinositol 3-Kinase/Akt Pathways Inhibits Cell Apoptosis in Human Hepatocytes Infect. Immun., November 1, 2002; 70(11): 6294 - 6301. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Huang, W. C. Powell, A. C. Khodavirdi, J. Wu, T. Makita, R. D. Cardiff, M. B. Cohen, H. M. Sucov, and P. Roy-Burman Prostatic Intraepithelial Neoplasia in Mice with Conditional Disruption of the Retinoid X Receptor{alpha} Allele in the Prostate Epithelium Cancer Res., August 15, 2002; 62(16): 4812 - 4819. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Meeting Abstracts Online |
