Loss of Ypk1 function causes rapamycin sensitivity, inhibition of translation initiation and synthetic lethality in 14-3-3-deficient yeast

Daniel Gelperin, Lynn Horton, Anne DeChant, Jack Hensold, Sandra Lemmon

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

14-3-3 proteins bind to phosphorylated proteins and regulate a variety of cellular activities as effectors of serine/threonine phosphorylation. To define processes requiring 14-3-3 function in yeast, mutants with increased sensitivity to reduced 14-3-3 protein levels were identified by synthetic lethal screening. One mutation was found to be allelic to YPK1, which encodes a Ser/Thr protein kinase. Loss of Ypk function causes hypersensitivity to rapamycin, similar to 14-3-3 mutations and other mutations affecting the TOR signaling pathway in yeast. Similar to treatment with rapamycin, loss of Ypk function disrupted translation, at least in part by causing depletion of eIF4G, a central adaptor protein required for cap-dependent mRNA translation initiation. In addition, Ypk1 as well as eIF4G protein levels were rapidly depleted upon nitrogen starvation, but not during glucose starvation, even though both conditions inhibit translation initiation. These results suggest that Ypk regulates translation initiation in response to nutrient signals, either through the TOR pathway or in a functionally related pathway parallel to TOR.

Original languageEnglish
Pages (from-to)1453-1464
Number of pages12
JournalGenetics
Volume161
Issue number4
StatePublished - Aug 1 2002
Externally publishedYes

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Sirolimus
14-3-3 Proteins
Yeasts
Starvation
Mutation
Proteins
Protein Biosynthesis
Threonine
Protein Kinases
Serine
Hypersensitivity
Nitrogen
Phosphorylation
Glucose
Food
Synthetic Lethal Mutations

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Loss of Ypk1 function causes rapamycin sensitivity, inhibition of translation initiation and synthetic lethality in 14-3-3-deficient yeast. / Gelperin, Daniel; Horton, Lynn; DeChant, Anne; Hensold, Jack; Lemmon, Sandra.

In: Genetics, Vol. 161, No. 4, 01.08.2002, p. 1453-1464.

Research output: Contribution to journalArticle

Gelperin, Daniel ; Horton, Lynn ; DeChant, Anne ; Hensold, Jack ; Lemmon, Sandra. / Loss of Ypk1 function causes rapamycin sensitivity, inhibition of translation initiation and synthetic lethality in 14-3-3-deficient yeast. In: Genetics. 2002 ; Vol. 161, No. 4. pp. 1453-1464.
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