This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Jiang, Y. Articles by Shi, Y. E. Search for Related Content PubMed PubMed Citation Articles by Jiang, Y. Articles by Shi, Y. E.

Synuclein, a Novel Heat-Shock Protein-Associated Chaperone, Stimulates Ligand-Dependent Estrogen Receptor Signaling and Mammary Tumorigenesis

North Shore Long Island Jewish Research Institute, Department of Radiation Oncology, Long Island Jewish Medical Center, Albert Einstein College of Medicine, New Hyde Park, New York

Synucleins are emerging as central players in the formation of pathologically insoluble deposits characteristic of neurodegenerative diseases. synuclein (SNCG), previously identified as a breast cancer-specific gene (BCSG1), is also highly associated with breast or ovarian cancer progression. However, the molecular targets of SNCG aberrant expression in breast cancer have not been identified. Here, we demonstrated a chaperone activity of SNCG in the heat-shock protein (Hsp)-based multiprotein chaperone complex for stimulation of estrogen receptor (ER)- signaling. As an ER--associated chaperone, SNCG participated in Hsp-ER- complex, enhanced the high-affinity ligand-binding capacity of ER-, and stimulated ligand-dependent activation of ER-. The SNCG-mediated stimulation of ER- transcriptional activity is consistent with its stimulation of mammary tumorigenesis in response to estrogen. These data indicate that SNCG is a new chaperone protein in the Hsp-based multiprotein chaperone complex for stimulation of ligand-dependent ER- signaling and thus stimulates hormone-responsive mammary tumorigenesis.

This article has been cited by other articles:

				T. Hibi, T. Mori, M. Fukuma, K. Yamazaki, A. Hashiguchi, T. Yamada, M. Tanabe, K. Aiura, T. Kawakami, A. Ogiwara, et al. Synuclein-{gamma} Is Closely Involved in Perineural Invasion and Distant Metastasis in Mouse Models and Is a Novel Prognostic Factor in Pancreatic Cancer Clin. Cancer Res., April 15, 2009; 15(8): 2864 - 2871. [Abstract] [Full Text] [PDF]

				I. Surgucheva, V. I. Shestopalov, and A. Surguchov Effect of {gamma}-Synuclein Silencing on Apoptotic Pathways in Retinal Ganglion Cells J. Biol. Chem., December 26, 2008; 283(52): 36377 - 36385. [Abstract] [Full Text] [PDF]

				P. J. Oort, T. A. Knotts, M. Grino, N. Naour, J.-P. Bastard, K. Clement, N. Ninkina, V. L. Buchman, P. A. Permana, X. Luo, et al. {gamma}-Synuclein Is an Adipocyte-Neuron Gene Coordinately Expressed with Leptin and Increased in Human Obesity J. Nutr., May 1, 2008; 138(5): 841 - 848. [Abstract] [Full Text] [PDF]

				W. S. Woods, J. M. Boettcher, D. H. Zhou, K. D. Kloepper, K. L. Hartman, D. T. Ladror, Z. Qi, C. M. Rienstra, and J. M. George Conformation-specific Binding of {alpha}-Synuclein to Novel Protein Partners Detected by Phage Display and NMR Spectroscopy J. Biol. Chem., November 23, 2007; 282(47): 34555 - 34567. [Abstract] [Full Text] [PDF]

				M. Ahmad, S. Attoub, M. N. Singh, F. L. Martin, and O. M. A. El-Agnaf {gamma}-Synuclein and the progression of cancer FASEB J, November 1, 2007; 21(13): 3419 - 3430. [Abstract] [Full Text] [PDF]

				S. V. Sheleg, J.-M. Peloponese, Y.-H. Chi, Y. Li, M. Eckhaus, and K.-T. Jeang Evidence for Cooperative Transforming Activity of the Human Pituitary Tumor Transforming Gene and Human T-Cell Leukemia Virus Type 1 Tax J. Virol., August 1, 2007; 81(15): 7894 - 7901. [Abstract] [Full Text] [PDF]

				V. K. Singh, Y. Zhou, J. A. Marsh, V. N. Uversky, J. D. Forman-Kay, J. Liu, and Z. Jia Synuclein-{gamma} Targeting Peptide Inhibitor that Enhances Sensitivity of Breast Cancer Cells to Antimicrotubule Drugs Cancer Res., January 15, 2007; 67(2): 626 - 633. [Abstract] [Full Text] [PDF]

				L.-J. Zhao, X.-L. Zhang, P. Zhao, J. Cao, M.-M. Cao, S.-Y. Zhu, H.-Q. Liu, and Z.-T. Qi Up-regulation of ERK and p38 MAPK signaling pathways by hepatitis C virus E2 envelope protein in human T lymphoma cell line J. Leukoc. Biol., August 1, 2006; 80(2): 424 - 432. [Abstract] [Full Text] [PDF]

				C. Rowell, D. M. Carpenter, and C. A. Lamartiniere Chemoprevention of Breast Cancer, Proteomic Discovery of Genistein Action in the Rat Mammary Gland J. Nutr., December 1, 2005; 135(12): 2953S - 2959S. [Abstract] [Full Text] [PDF]

				H. Liu, W. Liu, Y. Wu, Y. Zhou, R. Xue, C. Luo, L. Wang, W. Zhao, J.-D. Jiang, and J. Liu Loss of Epigenetic Control of Synuclein-{gamma} Gene as a Molecular Indicator of Metastasis in a Wide Range of Human Cancers Cancer Res., September 1, 2005; 65(17): 7635 - 7643. [Abstract] [Full Text] [PDF]

				H. Snyder, K. Mensah, C. Hsu, M. Hashimoto, I. G. Surgucheva, B. Festoff, A. Surguchov, E. Masliah, A. Matouschek, and B. Wolozin {beta}-Synuclein Reduces Proteasomal Inhibition by {alpha}-Synuclein but Not {gamma}-Synuclein J. Biol. Chem., March 4, 2005; 280(9): 7562 - 7569. [Abstract] [Full Text] [PDF]