title: Activation of transcription by progesterone receptor involves derepression of activation functions by a cofactor.
abstract: Hormone-induced progesterone receptors (PR) bound to response elements stimulate transcription initiation at target promoters through a mechanism that presumably involves cofactors or coactivators. To allow identification of such cofactors of transcriptional activation in a functional assay, we have established a reconstituted transcription system that is characterized by a specific loss of responsiveness to purified baculovirus-expressed wild type PR. In contrast to wild type PR, a C-terminally truncated PR mutant displayed strong activation potential in this system. As the purified recombinant full-length PR is capable of DNA binding, our results suggest that C-terminal sequences of PR mediate a cis-repression of N-terminal activation functions. Moreover, using this PR-nonresponsive transcription system, we identified and partially purified an activity from rat liver, termed COPRA (cofactor of PR activation), that restores transactivation by full-length PR. Characterization of COPRA revealed that this cofactor exhibits activator specificity and is not involved in basal transcription. We postulate that COPRA acts by relieving the repression of activation functions mediated by C-terminal sequences.
authors.affiliation: Institut für Zellbiologie (Tumorforschung), Universitätsklinikum, Essen, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Klotzbücher
authors.forename: C
authors.initials: C
authors.lastname: Schwerk
authors.forename: B
authors.initials: B
authors.lastname: Holewa
authors.forename: L
authors.initials: L
authors.lastname: Klein-Hitpass
mesh_terms: D000818:Animals; D002460:Cell Line; D002474:Cell-Free System; D004268:DNA-Binding Proteins / Q000235:genetics*; D017353:Gene Deletion; D005786:Gene Expression Regulation; D006801:Humans; D051381:Rats; D011980:Receptors, Progesterone / Q000235:genetics*; D011993:Recombinant Fusion Proteins / Q000235:genetics; D018411:Spodoptera / Q000166:cytology; D015534:Trans-Activators / Q000235:genetics*; D015533:Transcriptional Activation
chemical_list: D004268:DNA-Binding Proteins; D011980:Receptors, Progesterone; D011993:Recombinant Fusion Proteins; D015534:Trans-Activators