Download Molecular Biology of Steroid and Nuclear Hormone Receptors by Didier Picard (auth.), Leonard P. Freedman (eds.) PDF

By Didier Picard (auth.), Leonard P. Freedman (eds.)

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Additional info for Molecular Biology of Steroid and Nuclear Hormone Receptors

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VI. SUBNUCLEAR TRAFFICKING OF STEROID RECEPTORS What is the fate of steroid receptors that emerge in the nucleus following passage through the NPC? In vivo footprinting analyses have established that steroid receptors can rapidly locate specific target sites within the genome 26 Donald B. DeFranco (Zaretand Yamamoto 1984, ReiketaI1991). How does this occur, and what is the mechanism by which steroid receptors traffic within the nucleus? , speckles or foci), and not randomly distributed. For example, Van Steensel and co-workers found that endogenous GRs in a variety of cultured cell types collected into 1,000-2,000 small nuclear speckles in hormone-treated cells (van Steensel et al 1995a).

EMBO J. 10: 2569-2576. Sackey FNA, Hache RJG, Reich T, Kwast-Welfeld J, and Lefebvre YA (1996): Determinants of subcellular distribution of the glucocorticoid receptor. Mol. Endocrinol. 10: 1191-1205. Sanchez ER, Hirst M, Scherrer LC, Tang HY, Welsh MJ, Harmon JM, Simons SSJ, Ringold GM, and Pratt WB (1990): Hormone-free mouse glucocorticoid receptors overexpressed in Chinese hamster ovary cells are localized to the nucleus and are associated with both hsp70 and hsp90. J. BioI. Chern. 265: 20123-20130.

In support of this conclusion is the fact that newly synthesized RNA or RNA polymerase II did not co localize with GR speckles (van Steensel et al 1995a). In direct contrast to these results, different nuclear staining patterns of agonist-bound GR, as compared to antagonist-bound GR, were observed in living cells by Htun and co-workers, using a green fluorescent protein-GR fusion protein (Htun et aI1996). Since Htun and co-workers did not visualize sites of active transcription, it is not known what proportion of agonist-bound GRs visualized in their studies, if any, are actively involved in transcription.

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