{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T06:01:01Z","timestamp":1779343261746,"version":"3.51.4"},"reference-count":49,"publisher":"Rockefeller University Press","issue":"5","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1999,9,6]]},"abstract":"<jats:p>RAP46 is a eukaryotic cochaperone that associates with several proteins, including the heat shock protein hsp70\/hsc70 and the glucocorticoid receptor (GR). Here we show a downregulation of GR-mediated transactivation by RAP46 via a mechanism independent of a cytoplasmic action of this cochaperone. We demonstrate a specific cytoplasmic\u2013nuclear recruitment of RAP46 by the liganded GR that results in inhibition of the transactivation function of the receptor. A repeated sequence motif [EEX4]8 at the NH2 terminus of RAP46 or BAG-1L, a larger isoform of RAP46, is responsible for this downregulation of GR activity. BAG-1, a shorter isoform with only a duplication of the [EEX4] sequence, does not inhibit GR activity. The [EEX4]8 motif, when linked to an otherwise unrelated protein, abrogated the inhibitory action of endogenous RAP46 on GR-mediated transactivation. The nuclear effects of RAP46 and BAG-1L are specific since GR-mediated inhibition of AP-1 activity was not affected. These studies identify the [EEX4]8 sequence as a signature motif for inhibition of GR-mediated transactivation and demonstrate a specific nuclear action of a eukaryotic cochaperone in the regulation of GR activity.<\/jats:p>","DOI":"10.1083\/jcb.146.5.929","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T16:45:41Z","timestamp":1027701941000},"page":"929-940","update-policy":"https:\/\/doi.org\/10.1083\/jcb.crossmarkpolicy","source":"Crossref","is-referenced-by-count":71,"title":["A Nuclear Action of the Eukaryotic Cochaperone Rap46 in Downregulation of Glucocorticoid Receptor Activity"],"prefix":"10.1083","volume":"146","author":[{"given":"Jean","family":"Schneikert","sequence":"first","affiliation":[{"name":"aForschungszentrum Karlsruhe, Institute of Toxicology and Genetics, D-76021 Karlsruhe, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susanne","family":"H\u00fcbner","sequence":"additional","affiliation":[{"name":"aForschungszentrum Karlsruhe, Institute of Toxicology and Genetics, D-76021 Karlsruhe, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elke","family":"Martin","sequence":"additional","affiliation":[{"name":"aForschungszentrum Karlsruhe, Institute of Toxicology and Genetics, D-76021 Karlsruhe, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew C.B.","family":"Cato","sequence":"additional","affiliation":[{"name":"aForschungszentrum Karlsruhe, Institute of Toxicology and Genetics, D-76021 Karlsruhe, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"291","published-online":{"date-parts":[[1999,9,6]]},"reference":[{"key":"2023072901591438900_Arriza1991","first-page":"13","article-title":"Aldosterone actionperspectives from the cloning of the mineralocorticoid receptor","volume-title":"Aldosterone","author":"Arriza","year":"1991"},{"key":"2023072901591438900_Arrizaetal1987","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1126\/science.3037703","article-title":"Cloning of human mineralocorticoid receptor complementary DNAstructural and functional kinship with the glucocorticoid receptor","volume":"237","author":"Arriza","year":"1987","journal-title":"Science."},{"key":"2023072901591438900_Bardellietal1996","doi-asserted-by":"crossref","first-page":"6205","DOI":"10.1002\/j.1460-2075.1996.tb01009.x","article-title":"HGF receptor associates with the anti-apoptotic protein BAG-1 and prevents cell death","volume":"15","author":"Bardelli","year":"1996","journal-title":"EMBO (Eur. 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