Integration of Multiple Nutrient Cues and Regulation of Lifespan by Ribosomal Transcription Factor Ifh1

Ling Cai, Mark A. McCormick, Brian K. Kennedy, Benjamin P. Tu

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

Ribosome biogenesis requires an enormous commitment of energy and resources in growing cells. In budding yeast, the transcriptional coactivator Ifh1p is an essential regulator of ribosomal protein (RP) gene transcription. Here, we report that Ifh1p is dynamically acetylated and phosphorylated as a function of the growth state of cells. Ifh1p is acetylated at numerous sites in its N-terminal region by Gcn5p and deacetylated by NAD+-dependent deacetylases of the sirtuin family. Acetylation of Ifh1p is responsive to intracellular acetyl-CoA levels and serves to regulate the stability of Ifh1p. The phosphorylation of Ifh1p is mediated by protein kinase A and isdependent on TORC1 signaling. Thus, multiple nutrient-sensing mechanisms converge on Ifh1p. However, instead of modulating overall rates of RP gene transcription or cell growth, the nutrient-responsive phosphorylation of Ifh1p plays a more prominent role in the regulation of cellular replicative lifespan

Original languageEnglish (US)
Pages (from-to)1063-1071
Number of pages9
JournalCell Reports
Volume4
Issue number6
DOIs
StatePublished - Sep 26 2013

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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