Gamma synuclein, a novel heat-shock protein-associated chaperone, stimulates ligand-dependent estrogen receptor alpha signaling and mammary tumorigenesis.
Synucleins are emerging as central players in the formation of pathologically insoluble deposits characteristic of neurodegenerative diseases. gamma 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)-alpha signaling. As an ER-alpha-associated chaperone, SNCG participated in Hsp-ER-alpha complex, enhanced the high-affinity ligand-binding capacity of ER-alpha, and stimulated ligand-dependent activation of ER-alpha. The SNCG-mediated stimulation of ER-alpha 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-alpha signaling and thus stimulates hormone-responsive mammary tumorigenesis.
Jiang
Yangfu
Y
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 11040, USA.
Liu
Yiliang Ellie
YE
Goldberg
Itzhak D
ID
Shi
Y Eric
YE
D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D047628:Estrogen Receptor alpha; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism / Q000502:physiology; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism / Q000502:physiology; D006801:Humans; D008024:Ligands; D018832:Molecular Chaperones / Q000378:metabolism / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000502:physiology*; D011960:Receptors, Estrogen / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D051843:Synucleins; D015533:Transcriptional Activation; D014162:Transfection; D051845:gamma-Synuclein
D047628:Estrogen Receptor alpha; D018840:HSP70 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; D008024:Ligands; D018832:Molecular Chaperones; D009419:Nerve Tissue Proteins; D011960:Receptors, Estrogen; D051843:Synucleins; D051845:gamma-Synuclein