Project description:Cells need to coordinate gene expression with their metabolic states to maintain cell homeostasis and growth. However, how cells transduce nutrient availability to appropriate gene expression response via histone modifications remains poorly understood. Here, we report that glycolysis promotes H3K4me3 by activating Tpk2, the catalytic subunit of protein kinase A (PKA) via the Ras-cyclic AMP (cAMP) pathway. Further study showed that Tpk2 antagonizes Jhd2-catalyzed H3K4 demethylation by phosphorylating Jhd2 at S321 and S340 in response to glucose availability.Mechanistically, Tpk2-catalyzed Jhd2 phosphorylation inhibits its overall binding to chromatin and promotes its polyubiquitination by the E3 ubiquitin ligase Not4 and degradation by the proteasome. In addition, Tpk2-catalyzed Jhd2 phosphorylation also maintains H3K14ac by preventing the binding of Rpd3 to chromatin. By inhibiting the activity of Jhd2 and Rpd3, Tpk2-catalyzed Jhd2 phosphorylation regulates gene expression and promotes autophagy. Thus, regulation of Jhd2 by the Ras-cAMP-PKA pathway shed lights on how cells rewire their biological responses to glucose availability.
Project description:In this study, we used Saccharomyces cerevisiae to investigate the effects of GRX deletion on yeast chronological life span (CLS). Deletion of Grx1 or Grx2 shortened yeast CLS. Quantitative proteomics revealed that GRX deletion increased cellular ROS levels to activate Ras/PKA signal pathway. Our results provided new insights into mechanisms underlying aging process.
Project description:Comparison of the transcriptomes of Saccharomyces cerevisiae wild type FY23 and a PDE2 deletion mutant DJ28. Keywords = PDE2 Keywords = Ras/cAMP pathway Keywords: other
Project description:Asc1p and its essential orthologues in higher eukaryotes, as e.g. RACK1 in mammals, are involved in several distinct cellular signaling processes, but the implications of a total deletion have never been assessed in a comprehensive genome-wide manner. This study reveals the major cellular processes affected in a Saccharomyces cerevisiae Δasc1 deletion background via de novo proteome and transcriptome analysis, as well as subsequent phenotypical characterizations. The deletion of ASC1 reduces iron-uptake and causes nitrosative stress, both known indicators for hypoxia, which manifests in a shift of energy metabolism from respiration to fermentation in the Δasc1 strain. The impact of Asc1p in cellular metabolism is further expressed by its regulative role in the MAP kinase signal transduction pathways of invasive/filamentous growth, pheromone response and cell wall integrity. In the Δasc1 mutant strain aberrations from the expected cellular response, mediated by these pathways, can be observed and are linked to changes in protein abundances of pathway-targeted transcription factors. Evidence for the translational regulation of such transcription factors suggests that ribosomal Asc1p is involved in signal transduction pathways by controlling the biosynthesis of the respective final transcriptional regulators.
Project description:Comparison of the transcriptomes of Saccharomyces cerevisiae wild type FY23 and a PDE2 deletion mutant DJ28. Keywords = PDE2 Keywords = Ras/cAMP pathway