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A novel role of protein kinase Gcn2 in yeast tolerance to intracellular acid stress.
MedLine Citation:
PMID:  21919885     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Intracellular pH conditions many cellular systems but its mechanisms of regulation and perception are mostly unknown. We have identified two yeast genes important for tolerance to intracellular acidification caused by weak permeable acids. One corresponded to LEU2 and functions by removing the dependency of the leu2 mutant host strain on uptake of extracellular leucine. Leucine transport is inhibited by intracellular acidification and either leucine over-supplementation or over-expression of the transporter gene BAP2 improved acid growth. Another acid-tolerance gene is GCN2, encoding a protein kinase activated by uncharged tRNAs during amino acid starvation. Gcn2 phosphorylates eIF2α(Sui2) at Ser-51 and this inhibits general translation but activates that of Gcn4, a transcription factor for amino acid biosynthetic genes. Intracellular acidification activates Gcn2 probably by inhibition of amino acyl-tRNA synthetases because we observed accumulation of uncharged tRNAleu without leucine depletion. Gcn2 is required for leucine transport and a gcn2 null mutant is sensitive to acid stress if auxotroph for leucine. Gcn4 is required for neither leucine transport nor acid tolerance but a Ser-51--->Ala sui2 mutant is acid sensitive. This suggests that Gcn2, by phosphorylating eIF2α, may activate translation of an unknown regulator of amino acid transporters different from Gcn4.
Authors:
Guillem Hueso; Rafael Aparicio-Sanchis; Consuelo Montesinos; Silvia Lorenz; Jose R Murguia; Ramón Serrano
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-9-15
Journal Detail:
Title:  The Biochemical journal     Volume:  -     ISSN:  1470-8728     ISO Abbreviation:  -     Publication Date:  2011 Sep 
Date Detail:
Created Date:  2011-9-16     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  2984726R     Medline TA:  Biochem J     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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