PubMed · 14369345
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B POLLACK. 1955. Mental illness.. https://pubmed.ncbi.nlm.nih.gov/14369345/
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In Saccharomyces cerevisiae, Maf1 is essential for mediating the repression of transcription by RNA polymerase (pol) III in response to diverse cellular conditions. These conditions activate distinct signaling pathways that converge at or above Maf1. Thus, Maf1-dependent repression is thought to involve a common set of downstream inhibitory effects on the pol III machinery. Here we provide support for this view and define two steps in Maf1-dependent transcriptional repression. We show that chlorpromazine (CPZ)-induced repression of pol III transcription is achieved by inhibiting de novo assembly of transcription factor (TF) IIIB onto DNA as well as the recruitment of pol III to preassembled TFIIIB.DNA complexes. Additionally Brf1 was identified as a target of repression in extracts of CPZ-treated cells. Maf1-Brf1 and Maf1-pol III interactions were implicated in the inhibition of TFIIIB.DNA complex assembly and polymerase recruitment by recombinant Maf1. Co-immunoprecipitation experiments confirmed these interactions in yeast extracts and demonstrated that Maf1 does not differentially sequester Brf1 or pol III under repressing conditions. The results suggest that Maf1 functions by a non-stoichiometric mechanism to repress pol III transcription.
In this study, the effects of chlorpromazine (CPZ) on lipid order and motion in saturated (DMPC, DMPG) and unsaturated (SOPC) liposome membranes were investigated by electron spin resonance (ESR) spin labeling technique. We have shown that above the main phase transition temperature of membrane lipids (T(M)), CPZ slightly increases lipid order in membranes without cholesterol, whereas below T(M) it has a strong opposite effect. Addition of 30 mol% of cholesterol into DMPC and SOPC membranes changes significantly the CPZ effects both above and below T(M). Additionally, above T(M), the ordering effect of CPZ on pure SOPC membrane is stronger at pH 7.4 than at pH 9.0, whereas below T(M), as well as in the presence of cholesterol, pH does not seem to play a role in CPZ effect on both membranes. Because of the strong influence of membrane composition on CPZ effect on membranes, the use of cholesterol as a marker of CPZ photosensitized reactions has been discussed.
Human alpha1-acid glycoprotein (hAGP) is a plasma glycoprotein that functions as a major carrier of basic ligands. This is the first report of the recombinant hAGP (rhAGP). In this study, rhAGP was expressed in the methylotropic yeast Pichia pastoris (GS115) using the expression vector, pPIC9, and then purified by anionic exchange, hydrophobic interaction, and gel filtration chromatography. The molecular weight of rhAGP was much lower than that of hAGP, because of the difference in glycan chain content. Results of glycopeptidase F digestion suggest that the peptide moiety of rhAGP was the same as that of hAGP. The results of circular dichroism spectra measurement indicated that rhAGP predominantly formed a beta-sheet-rich structure that was the same as that of hAGP and typical of the lipocalin family. From the experiments using AGP-binding drugs (chlorpromazine, warfarin, and progesterone) and quinaldine red as a probe for the binding site, it was indicated that rhAGP also had the same ligand-binding capacity and binding site structure as hAGP. These findings strongly suggest that this recombinant hAGP (rhAGP) is very useful for the exploration of the ligand-binding site and biological function of hAGP.