title: Inositol pyrophosphates regulate cell growth and the environmental stress response by activating the HDAC Rpd3L.
abstract: Cells respond to stress and starvation by adjusting their growth rate and enacting stress defense programs. In eukaryotes this involves inactivation of TORC1, which in turn triggers downregulation of ribosome and protein synthesis genes and upregulation of stress response genes. Here we report that the highly conserved inositol pyrophosphate (PP-IP) second messengers (including 1-PP-IP5, 5-PP-IP4, and 5-PP-IP5) are also critical regulators of cell growth and the general stress response, acting in parallel with the TORC1 pathway to control the activity of the class I histone deacetylase Rpd3L. In fact, yeast cells that cannot synthesize any of the PP-IPs mount little to no transcriptional response to osmotic, heat, or oxidative stress. Furthermore, PP-IP-dependent regulation of Rpd3L occurs independently of the role individual PP-IPs (such as 5-PP-IP5) play in activating specialized stress/starvation response pathways. Thus, the PP-IP second messengers simultaneously activate and tune the global response to stress and starvation signals.
authors: Department of Molecular and Cellular Biology, University of Arizona, Tucson, AZ 85721-0206, USA.
authors: Jeremy
authors: J
authors: Worley
authors: Xiangxia
authors: X
authors: Luo
authors: Andrew P
authors: AP
authors: Capaldi
mesh_terms: D015966:Gene Expression Regulation, Fungal / Q000187:drug effects; D056284:Histone Deacetylase 1 / Q000235:genetics / Q000378:metabolism*; D007295:Inositol Phosphates / Q000494:pharmacology*; D000076222:Mechanistic Target of Rapamycin Complex 1; D046912:Multiprotein Complexes / Q000378:metabolism; D009994:Osmolar Concentration; D018384:Oxidative Stress; D017856:Phosphotransferases (Phosphate Group Acceptor) / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D015290:Second Messenger Systems; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D013696:Temperature
chemical_list: D007295:Inositol Phosphates; D046912:Multiprotein Complexes; D029701:Saccharomyces cerevisiae Proteins; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases; D017856:Phosphotransferases (Phosphate Group Acceptor); C098863:KCS1 protein, S cerevisiae; C099438:inositol hexakisphosphate kinase; D056284:Histone Deacetylase 1
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