Yeast RSP5 and its human homolog hRPF1 potentiate hormone-dependent activation of transcription by human progesterone and glucocorticoid receptors.
We have developed a system in Saccharomyces cerevisiae in which agonist-dependent transcriptional activity of the human progesterone receptor (hPR) is elevated to the point that it compromises cell growth. Screens for suppressors of this phenotype led to the demonstration that RSP5 is involved in hPR transactivation. Expression of RSP5 in yeast cells potentiated hPR and human glucocorticoid receptor (hGR) transcriptional activity and increased the efficacy of weak agonists of these receptors. Remarkably, expression of this yeast protein in mammalian cells had a similar effect on PR and GR transcriptional activity. Importantly, a human homolog of RSP5, hRPF1, functioned identically in mammalian cells. Previously, it has been demonstrated that RSP5 overexpression in yeast cells suppressed mutations within SPT3, a protein which interacts with the TATA-box-binding protein (TBP), suggesting that RSP5 and SPT3 operate in the same regulatory pathway. In support of this observation, we have shown that SPT3 enhances the activity of RSP5 on GR and PR when tested in yeast or mammalian cells. We conclude from these experiments that the regulatory pathways in which RSP5 and SPT3 operate in yeast cells are conserved in higher eukaryotes. Additionally, since SPT3 has been shown to contact yeast TBP directly and is the likely homolog of human TBP-associated factor TAFII18, we propose that RSP5/hRPF1 and SPT3 establish a functional link between activated PR and GR and the general transcription apparatus.
Imhof
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Department of Pharmacology, Duke University Medical Center, Durham, North Carolina 27710, USA.
McDonnell
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D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D056827:Endosomal Sorting Complexes Required for Transport; D005656:Fungal Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008025:Ligases / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation; D011965:Receptors, Glucocorticoid / Q000235:genetics* / Q000378:metabolism; D011980:Receptors, Progesterone / Q000235:genetics* / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D015533:Transcriptional Activation; D043743:Ubiquitin-Protein Ligase Complexes; D044767:Ubiquitin-Protein Ligases
D017931:DNA Primers; D056827:Endosomal Sorting Complexes Required for Transport; D005656:Fungal Proteins; D011965:Receptors, Glucocorticoid; D011980:Receptors, Progesterone; C075582:SPT3 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D043743:Ubiquitin-Protein Ligase Complexes; D044767:Ubiquitin-Protein Ligases; D008025:Ligases; C469287:RSP5 protein, S cerevisiae