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The growth of both normal and transformed epithelial cells of the female reproductive system is stimulated by estrogens, mainly through the activation of estrogen receptor alpha (ERalpha), which is a ligand-regulated transcription factor. The selective ER modulator tamoxifen (TAM) has been widely used as an ER antagonist in breast tumor; however, long-term(More)
We have detected nuclear localization signals within the 795 amino acid rat glucocorticoid receptor. Using a transient expression assay, we monitored by immunofluorescence the subcellular distribution of receptor derivatives and beta-galactosidase-receptor fusion proteins. Two distinct nuclear localization signals, NL1 and NL2, were defined. NL1 maps to a(More)
The estrogen receptor (ER) can be activated as a transcription factor either by binding of cognate estrogenic ligand or, indirectly, by a variety of other extracellular signals. As a first step towards elucidating the mechanism of 'steroid-independent activation' of the ER by the epidermal growth factor (EGF), we have mapped the ER target domain and(More)
The higher incidence of thyroid carcinoma (TC) in women during reproductive years compared with men and the increased risk associated with the therapeutic use of estrogens have suggested a pathogenetic role exerted by these steroids in the development of TC. In the present study, we evaluated the potential of 17beta-estradiol (E2), genistein (G), and(More)
During differentiation of lymphocytes into antibody-producing cells, an immunoglobulin kappa variable-region gene is transcriptionally activated by rearrangement linking it to a kappa constant (C kappa) region gene which is already transcribed prior to somatic rearrangement. The presence of a transcriptional enhancer element within the large intron of the(More)
  • D Picard
  • 2002
Heat-shock protein 90 (Hsp90) is an abundant and highly conserved molecular chaperone that is essential for viability in eukaryotes. Hsp90 fulfills a housekeeping function in contributing to the folding, maintenance of structural integrity and proper regulation of a subset of cytosolic proteins. A remarkable proportion of its substrates are proteins(More)
A growing body of evidence concerning estrogen effects cannot be explained by the classic model of hormone action, which involves the binding to estrogen receptors (ERs) alpha and ERbeta and the interaction of the steroid-receptor complex with specific DNA sequences associated with target genes. Using c-fos proto-oncogene expression as an early molecular(More)
The highly abundant molecular chaperone Hsp90 functions with assistance from auxiliary factors, collectively referred to as Hsp90 cochaperones, and the Hsp70 system. Hsp104, a molecular chaperone required for stress tolerance and for maintenance of [psi(+)] prions in the budding yeast Saccharomyces cerevisiae, appears to collaborate only with the Hsp70(More)
Those that efface themselves in the action tend to be forgotten. But molecular chaperones are always there, often serving as equal partners. Because of their intrinsic functional frailty, a large number of signaling molecules have come to depend on molecular chaperones, notably the Hsp90 chaperone machine. This applies to the subset of nuclear receptors(More)
We demonstrate that the hormone-binding domain (HBD) of the human estrogen receptor (ER) can function as an autonomous regulatory domain in the budding yeast, Saccharomyces cerevisiae. As in mammalian cells, the HBD can subject the activity of a heterologous protein, which is fused to it, to hormonal control. Thus, a chimeric transcriptional activator(More)