Thioredoxin is transcriptionally induced upon activation of heat shock factor 2. 1997

S Leppä, and L Pirkkala, and S C Chow, and J E Eriksson, and L Sistonen
Turku Centre for Biotechnology, University of Turku, Abo Akademi University, FIN-20521 Turku, Finland. lea.sistonen@btk.utu.fi

Heat shock gene expression is differentially regulated in cells exposed to stress stimuli and in cells undergoing processes of differentiation and development. Regulation of the classical heat shock response is mediated by heat shock factor 1 (HSF1), whereas heat shock factor 2 (HSF2) is activated in certain differentiating cells, for example during hemin-mediated differentiation of human K562 erythroleukemia cells. Hence, the signaling pathways leading to induction of heat shock gene expression upon different stimuli are likely to be distinct. We have used RNA arbitrarily primed polymerase chain reaction to identify genes that are differentially regulated upon activation of HSF1 and HSF2. In this study, we report that thioredoxin (TRX) expression is induced in K562 cells in response to hemin in an HSF2-dependent manner. Increased TRX expression was primarily detected on the transcriptional level, subsequently leading to elevated TRX mRNA and protein levels. Hemin treatment caused no reduction in cellular glutathione concentrations, indicating that the increased TRX expression was not due to oxidative stress. Studies using cell lines where overexpression of the HSF2-beta isoform represses HSF2 activation implied that active HSF2 is required for transcriptional induction of TRX. Unlike HSF2, activation of HSF1 did not induce TRX expression. Taken together, our results suggest that HSF1 and HSF2 may regulate distinct target genes, and activation of HSF2 could be involved in the regulation of TRX expression during hemin-mediated differentiation of K562 cells.

UI MeSH Term Description Entries
D002454 Cell Differentiation Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs. Differentiation, Cell,Cell Differentiations,Differentiations, Cell
D004268 DNA-Binding Proteins Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases. DNA Helix Destabilizing Proteins,DNA-Binding Protein,Single-Stranded DNA Binding Proteins,DNA Binding Protein,DNA Single-Stranded Binding Protein,SS DNA BP,Single-Stranded DNA-Binding Protein,Binding Protein, DNA,DNA Binding Proteins,DNA Single Stranded Binding Protein,DNA-Binding Protein, Single-Stranded,Protein, DNA-Binding,Single Stranded DNA Binding Protein,Single Stranded DNA Binding Proteins
D005786 Gene Expression Regulation Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation. Gene Action Regulation,Regulation of Gene Expression,Expression Regulation, Gene,Regulation, Gene Action,Regulation, Gene Expression
D005978 Glutathione A tripeptide with many roles in cells. It conjugates to drugs to make them more soluble for excretion, is a cofactor for some enzymes, is involved in protein disulfide bond rearrangement and reduces peroxides. Reduced Glutathione,gamma-L-Glu-L-Cys-Gly,gamma-L-Glutamyl-L-Cysteinylglycine,Glutathione, Reduced,gamma L Glu L Cys Gly,gamma L Glutamyl L Cysteinylglycine
D006360 Heat-Shock Proteins Proteins which are synthesized in eukaryotic organisms and bacteria in response to hyperthermia and other environmental stresses. They increase thermal tolerance and perform functions essential to cell survival under these conditions. Stress Protein,Stress Proteins,Heat-Shock Protein,Heat Shock Protein,Heat Shock Proteins,Protein, Stress
D006427 Hemin Chloro(7,12-diethenyl-3,8,13,17-tetramethyl-21H,23H-porphine-2,18-dipropanoato(4-)-N(21),N(22),N(23),N(24)) ferrate(2-) dihydrogen. Ferriprotoporphyrin,Hematin,Alkaline Hematin D-575,Chlorohemin,Ferrihaem,Ferriheme Chloride,Ferriprotoporphyrin IX,Ferriprotoporphyrin IX Chloride,Panhematin,Protohemin,Protohemin IX,Alkaline Hematin D 575,Chloride, Ferriheme,Chloride, Ferriprotoporphyrin IX,Hematin D-575, Alkaline
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000076249 Heat Shock Transcription Factors Heat and cold stress-inducible, transcription factors that bind to inverted 5'-NGAAN-3' pentamer DNA sequences and are regulated by POLY-ADP-RIBOSYLATION. They play essential roles as transcriptional activators of the HEAT-SHOCK RESPONSE by inducing expression of large classes of MOLECULAR CHAPERONES and heat-shock proteins. They also function in DNA REPAIR; transcriptional reactivation of latent HIV-1; and pre-mRNA processing and nuclear export of HSP70 HEAT-SHOCK PROTEINS during heat stress. Heat Stress Transcription Factor,Plant Heat Shock Factor,Heat Shock Factor Protein 1,Heat Shock Factor, Plant,Heat Shock Transcription Factor,Heat Shock Transcription Factor 1,Heat Stress Transcription Factors,Plant Heat Shock Factors
D013879 Thioredoxins Hydrogen-donating proteins that participates in a variety of biochemical reactions including ribonucleotide reduction and reduction of PEROXIREDOXINS. Thioredoxin is oxidized from a dithiol to a disulfide when acting as a reducing cofactor. The disulfide form is then reduced by NADPH in a reaction catalyzed by THIOREDOXIN REDUCTASE. Thioredoxin,Thioredoxin 1,Thioredoxin 2,Thioredoxin-1,Thioredoxin-2
D014157 Transcription Factors Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process. Transcription Factor,Factor, Transcription,Factors, Transcription

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