Inositol Pyrophosphates Regulate Cell Growth and the Environmental Stress Response by Activating the HDAC Rpd3L

Jeremy Worley, Xiangxia Luo, Andrew P. Capaldi

Research output: Contribution to journalArticle

43 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1476-1482
Number of pages7
JournalCell Reports
Volume3
Issue number5
DOIs
StatePublished - May 30 2013

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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