Saccharomyces cerevisiae As a Model System to Study Steroid Hormone Receptors

摘要: The human estrogen (ER) and progesterone receptor (PR) are members of the steroid superfamily ligand-dependent transcription factors (Evans, 1988). cloning cDNAs for these receptors — ER in 1986 (Green et al, 1986) hPR 1987 (Misrahi 1987) their subsequent expression heterologous cell types permitted reconstitution hormone-responsive systems that have been amenable to genetic analysis. availability systems, coupled with existing biochemical techniques, has last ten years advanced our understanding considerably. Currently, we believe hormone signal transduction pathway is comprised multiple steps can be genetically or pharmacologically separated (McDonnell, 1995) A general outline proposed shown Figure 1. In absence hormone, sex (SRs) reside a transcriptionally latent form nuclei target cells (Beato 1987). These inactive biochemically sequestered large macromolecular complex containing series associated heat-shock proteins (Bagchi 1991; Pratt, 1990; Smith Toft, 1993). role vivo unknown. However, it postulated they involved folding maintaining state within (Smith Upon interaction cognate SRs undergo conformational change (Allan 1992; McDonnell 1995). This event promotes displacement heat -shock other proteins, permitting dimerization association activated specific DNA response elements (SREs) located regulatory regions gene promoters 1987; Kumar Chambon, Coincident this change, possibly as consequence it, phosphorylations Denner 1989; Takimoto 1992). resulting biological ligand determined by promoter context DNA-bound (Tora 1988; Tzukerman 1994). precise mechanism which affect unknown, although hormone-activated PR stabilize formation pre-initiation when assayed vitro (Klein-Hitpass 1990)