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Rand JD and Grant CM  (2006) The thioredoxin system protects ribosomes against stress-induced aggregation. Mol Biol Cell 17(1):387-401

Abstract: We previously showed that thioredoxins are required for dithiothreitol (DTT) tolerance, suggesting they maintain redox homeostasis in response to both oxidative and reductive stress conditions. In this present study, we screened the complete set of viable deletion strains in Saccharomyces cerevisiae for sensitivity to DTT to identify cell functions involved in resistance to reductive stress. We identified 195 mutants, whose gene products are localized throughout the cell. DTT-sensitive mutants were distributed among most major biological processes, but they particularly affected gene expression, metabolism, and the secretory pathway. Strikingly, a mutant lacking TSA1, encoding a peroxiredoxin, showed a similar sensitivity to DTT as a thioredoxin mutant. Epistasis analysis indicated that thioredoxins function upstream of Tsa1 in providing tolerance to DTT. Our data show that the chaperone function of Tsa1, rather than its peroxidase function, is required for this activity. Cells lacking TSA1 were found to accumulate aggregated proteins, and this was exacerbated by exposure to DTT. Analysis of the protein aggregates revealed that they are predominantly composed of ribosomal proteins. Furthermore, aggregation was found to correlate with an inhibition of translation initiation. We propose that Tsa1 normally functions to chaperone misassembled ribosomal proteins, preventing the toxicity that arises from their aggregation.

Status: Published Type: Journal Article | Research Support, Non-U.S. Gov't PubMed ID: 16251355

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AAT2 ADH1 ADK1 AFR1 AKR1 ANP1 APQ13 ARO2 ARP8 ARV1
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ARX1 ATP12 ATP2 BEM1 BUB3 BUD19 BUD22 BUD23 BUD25 BUD30
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BUD32 BUD7 CBP2 CHC1 CLC1 CNB1 COX14 CRD1 CRZ1 CSG2
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CYC8 DBP7 DOA1 DOA4 DOC1 ERG2 ERG24 ERG6 ERO1 FAB1
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FEN2 FUN12 FYV5 FYV6 GAL11 GCR2 GET1 GET3 GLO3 GND1
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IES6 IMG1 IMP2' IRA2 IRE1 IWR1 KSP1 LDB7 MAP1 MNN9
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MON2 MOT2 MRM2 MRPL23 MRPS28 MSR1 NAM2 NOT5 NPR2 NPT1
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Topics Genes linked to topics (#91 - 100 )
PER1 PFK2 PGD1 PHO2 PHO88 PHR1 PKR1 PRO1 PRP18 PRS3
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RAD50 RAD6 RAI1 RBK1 REG1 RIB1 RNR1 RNR4 ROX3 RPB9
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RPE1 RPL13B RPL16B RPL1B RPL27A RPL3 RPL31A RPL33A RPL35A RPL39
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RPL7B RPP1B RPS12 RPS13 RPS2 RPS20 RPS22A RPS27B RPS3 RPS6A
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RRN10 SAC1 SAC6 SAC7 SET3 SFP1 SHP1 SIN4 SIW14 SKN7
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SLK19 SNF1 SNF7 SNT1 SPF1 SPO19 SPT3 SRB5 SSE1 SSH1
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SSN8 SSQ1 SWA2 SWS2 TEF1 TOM70 TPD3 TPS1 TRS33 TRX1
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TRX2 TSA1 TUP1 UBI4 URE2 VMA10 VMA13 VMA16 VMA2 VMA21
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VMA22 VMA3 VMA7 VMA8 VPH2 VPS1 VPS16 VPS17 VPS20 VPS27
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Topics Genes linked to topics (#181 - 188 )
VPS33 VPS34 VPS45 VPS5 VPS54 YAP1 YDJ1 YVH1
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