The intersection between stress responses and inositol pyrophosphates in Saccharomyces cerevisiae
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MINI-REVIEW
The intersection between stress responses and inositol pyrophosphates in Saccharomyces cerevisiae Victoria A. Morrissette1 · Ronda J. Rolfes1 Received: 14 March 2020 / Revised: 9 April 2020 / Accepted: 11 April 2020 © Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Saccharomyces cerevisiae adapts to oxidative, osmotic stress and nutrient deprivation through transcriptional changes, decreased proliferation, and entry into other developmental pathways such as pseudohyphal formation and sporulation. Inositol pyrophosphates are necessary for these cellular responses. Inositol pyrophosphates are molecules composed of the phosphorylated myo-inositol ring that carries one or more diphosphates. Mutations in the enzymes that metabolize these molecules lead to altered patterns of stress resistance, altered morphology, and defective sporulation. Mechanisms to alter the synthesis of inositol pyrophosphates have been recently described, including inhibition of enzyme activity by oxidation and by phosphorylation. Cells with increased levels of 5-diphosphoinositol pentakisphosphate have increased nuclear localization of Msn2 and Gln3. The altered localization of these factors is consistent with the partially induced environmental stress response and increased expression of genes under the control of Msn2/4 and Gln3. Other transcription factors may also exhibit increased nuclear localization based on increased expression of their target genes. These transcription factors are each regulated by TORC1, suggesting that TORC1 may be inhibited by inositol pyrophosphates. Inositol pyrophosphates affect stress responses in other fungi (Aspergillus nidulans, Ustilago maydis, Schizosaccharomyces pombe, and Cryptococcus neoformans), in human and mouse, and in plants, suggesting common mechanisms and possible novel drug development targets. Keywords Saccharomyces cerevisiae · Inositol pyrophosphates · Stress response · Pseudohyphae · TORC1 Abbreviations PtdIns(4,5)P2 Phosphatidylinositol 4,5-bisphosphate IP3 and InsP3 Inositol (1,4,5) trisphosphate IP4 and InsP4 Inositol (1,3,4,5) tetraphosphate IP5 and InsP5 Inositol (1,3,4,5,6) pentaphosphate IP6 and InsP6 Inositol (1,2,3,4,5,6) hexakisphosphate 5-IP7 and 5PP-InsP5 5-Diphosphoinositol pentakisphosphate 1-IP7 and 1PP-InsP5 1-Diphosphoinositol pentakisphosphate IP8 and 1,5PP-InsP4 1,5-Diphosphoinositol tetrakisphosphate
Communicated by M. Kupiec. * Ronda J. Rolfes [email protected] 1
Department of Biology, Georgetown University, Reiss Science Building 406, Washington, DC 20057, USA
IP7 Either of the two isoforms (5-IP7 or 1-IP7) PP-InsPs General term to refer to all of inositol pyrophosphates together, IP7 and IP8 HDAC Histone deacetylase complex ESR Environmental stress response iESR Induced ESR rESR Repressed ESR RiBi Ribosome biogenesis
Introduction The yeast Saccharomyces cerevisiae responds to cellular stress through dramatic and global changes in gene expression, translation, and protein/enzyme activity. The environmen
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