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Lawrence CL, et al.  (2004) Evidence of a new role for the high-osmolarity glycerol mitogen-activated protein kinase pathway in yeast: regulating adaptation to citric acid stress. Mol Cell Biol 24(8):3307-23

Abstract: Screening the Saccharomyces cerevisiae disruptome, profiling transcripts, and determining changes in protein expression have identified an important new role for the high-osmolarity glycerol (HOG) mitogen-activated protein kinase (MAPK) pathway in the regulation of adaptation to citric acid stress. Deletion of HOG1, SSK1, PBS2, PTC2, PTP2, and PTP3 resulted in sensitivity to citric acid. Furthermore, citric acid resulted in the dual phosphorylation, and thus activation, of Hog1p. Despite minor activation of glycerol biosynthesis, the inhibitory effect of citric acid was not due to an osmotic shock. HOG1 negatively regulated the expression of a number of proteins in response to citric acid stress, including Bmh1p. Evidence suggests that BMH1 is induced by citric acid to counteract the effect of amino acid starvation. In addition, deletion of BMH2 rendered cells sensitive to citric acid. Deletion of the transcription factor MSN4, which is known to be regulated by Bmh1p and Hog1p, had a similar effect. HOG1 was also required for citric acid-induced up-regulation of Ssa1p and Eno2p. To counteract the cation chelating activity of citric acid, the plasma membrane Ca(2+) channel, CCH1, and a functional vacuolar membrane H(+)-ATPase were found to be essential for optimal adaptation. Also, the transcriptional regulator CYC8, which mediates glucose derepression, was required for adaptation to citric acid to allow cells to metabolize excess citrate via the tricarboxylic acid (TCA) cycle. Supporting this, Mdh1p and Idh1p, both TCA cycle enzymes, were up-regulated in response to citric acid.

Status: Published Type: Journal Article PubMed ID: 15060153

Topics addressed in this paper

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Topics Genes linked to topics (#1 - 10 )
ADE4 AFT1 AIM18 AMS1 ARO2 BCK1 BMH1 BMH2 BUB1 CAX4
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Topics Genes linked to topics (#11 - 20 )
CCH1 CCW14 CKA1 CLC1 CPR3 CPR4 CYC8 DRS2 END3 ENO2
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Topics Genes linked to topics (#21 - 30 )
ERG2 ERG3 ERG4 FBP1 FES1 FRE8 GLY1 HFA1 HOG1 IDH1
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Topics Genes linked to topics (#31 - 40 )
IFM1 IMP1 ISC1 LYS5 MDH1 MGM101 MSK1 MSN4 MTF1 PBS2
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Topics Genes linked to topics (#41 - 50 )
PEP3 PEP7 PNS1 POC4 PTC2 PTK2 PTP2 PTP3 RPL21A RRD1
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Topics Genes linked to topics (#51 - 60 )
RTN2 RVS167 SHP1 SKY1 SNF2 SOD1 SOK2 SSA1 SSK1 SWA2
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Topics Genes linked to topics (#61 - 70 )
TAF14 THR1 THR4 TPD3 TPS1 UAF30 VMA1 VMA16 VMA2 VMA22
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Topics Genes linked to topics (#71 - 80 )
VMA3 VMA5 VMA6 VMA7 VMA8 VPS16 VPS33 YAR1 YCL007C YEL045C
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Topics Genes linked to topics (#81 - 86 )
YKL102C YKL169C YLR326W YLR334C YLR346C YOR331C
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