Role of co-activators and co-repressors in the mechanism of steroid/thyroid receptor action.

作者：Hirotaka Shibata, Thomas E. Spencer, Sergio A. Oñate, Guido W Jenster, Sophia Y. Tsai, Ming-Ming Tsai, Bert W. O’Malley · 发表于：PubMed · 年份：1997 · 被引用次数：536 · 研究领域：Estrogen and related hormone effects

Steroid/thyroid hormone receptors are ligand-dependent transcription factors that regulate diverse aspects of growth, development, and homeostasis by binding as homodimers or heterodimers to their cognate DNA response elements to modulate transcription of target genes. Transactivation by steroid/ thyroid hormone receptors involves a conserved AF-2 domain located in the distal carboxy-terminus of the receptors. The existence of co-factors, termed co-activators or adapters, was first suggested by transcriptional squelching between progesterone receptors and estrogen receptors. Co-repressors were also postulated to contribute to the silencing function of unliganded thyroid hormone receptor (TR). The yeast two-hybrid system and Far-Western blotting have been used to identify several proteins that interact with members of the steroid/thyroid hormone receptor superfamily in a ligand-sensitive manner. Our laboratory cloned the first functional co-activator, termed steroid receptor co-activator-one (SRC-1), that appears to be a general co-activator for all steroid receptors tested and enhances transactivation of steroid hormone-dependent target genes. Subsequently, many more putative co-activators have been reported, including the SRC-1 related proteins, TIF2 and GRIP1, and other putative and unrelated co-activators such as ARA70, Trip1, RIP140, and TIF1. In addition, another co-activator, CREB-binding protein (CBP), has been shown to enhance steroid receptor-dependent target gene tr...