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Cited by 134 publications
(81 citation statements)
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“…GR, a member of the nuclear receptor superfamily, mediates glucose homeostasis, immune modulation, cellular growth and differentiation, and numerous other physiological responses in a wide variety of tissues (33)(34)(35)(36). Unlike many other sex steroid receptors that are localized predominantly to the nucleus, GR is normally sequestered in a preactive state in the cytosol, bound in a complex that includes multiple heat shock proteins (HSP56, 70, and 90) (33)(34)(35)(37)(38)(39)(40). Upon steroid binding, GR conformation is altered, unmasking a nuclear localization signaling motif and a DNA-binding domain.…”
Section: Discussionmentioning
confidence: 99%
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“…GR, a member of the nuclear receptor superfamily, mediates glucose homeostasis, immune modulation, cellular growth and differentiation, and numerous other physiological responses in a wide variety of tissues (33)(34)(35)(36). Unlike many other sex steroid receptors that are localized predominantly to the nucleus, GR is normally sequestered in a preactive state in the cytosol, bound in a complex that includes multiple heat shock proteins (HSP56, 70, and 90) (33)(34)(35)(37)(38)(39)(40). Upon steroid binding, GR conformation is altered, unmasking a nuclear localization signaling motif and a DNA-binding domain.…”
Section: Discussionmentioning
confidence: 99%
“…Once in the nucleus, GR binds as a homodimer in a head-to-head manner to its cis-acting DNA recognition element, the GRE (consensus GRE half-site, TGTTCT). GR also has been shown to participate through protein-protein interactions with other cofactors (co-activators/co-repressors), leading to either positive or negative effects on transcription of specific glucocorticoid-responsive genes (37,(39)(40)(41)(42)(43)(44)(45).…”
Section: Discussionmentioning
confidence: 99%
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“…Members of the family share several functional and structural similarities such as a variable N-terminus containing a transactivation function (AF-1), a centrally located DNA binding domain (DBD) consisting of two highly conserved zinc ®nger motifs and, Cterminally of the DBD, a region involved in binding of ligand, dimerization and transactivation, referred to as the ligand binding domain (LBD) (Gronemeyer and Laudet, 1995). The nuclear receptor family includes receptors for estrogens, progestins, androgens, glucocorticoids, mineralocorticoids (Beato et al, 1996), thyroid hormone, fatty acids and vitamin D3. The majority of nuclear receptor family members consists of a steadily growing number of receptors for which the ligand is unknown, the so called orphan receptors (Mangelsdorf and Evans, 1995).…”
Section: Introductionmentioning
confidence: 99%
“…This binding in turn releases the chaperones, which allows the receptor to traverse the nuclear membrane and initiate transcription of steroid-responsive genes. 4,107,108 This biochemical activation of nuclear redistribution can be temporarily suppressed with geldanamycin, which disrupts the molecular binding of Hsp90 to glucocorticoid receptor, yet when the cytoskeleton is depolymerized with cytochalasin-D treatment, the process resumes normal transport speeds. This indicates the necessity of the cytoskeleton in this process, 29,78,115 although the specific mechanism of this nucleocytoplasmic transport is still unclear.…”
Section: Additional Cytoskeletal-associated Proteinsmentioning
confidence: 99%