Thioredoxin modulates activator protein 1 (AP-1) activity and p27Kip1 degradation through direct interaction with Jab1

Hwang, Chae Young; Ryu, Yeung Sook; Chung, Min; Kim, Kwang Dong; Park, Sung Sup; Chae, Suhn-Kee; Chae, Ho Zoon; Kwon, Ki‐Sun

doi:10.1038/sj.onc.1208116

Cited by 65 publications

(29 citation statements)

References 41 publications

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“…Even Y2H binary interactions involving TRX targets isolated by another in vivo method failed in classical Y2H yeast strains (26). The poor efficiency of classical Y2H systems to reveal TRX targets has been observed in previous library screenings (28)(29)(30)49), and only a few TRX partners have been isolated up to now (27)(28)(29)(30)(31). Some TRXinteracting partners, such as ASK1 (50), the S Locus receptor kinase SRK (51), and the Cf-9 protein (52) were also revealed, but in which TRXs were captured as the targets of these proteins.…”

Section: Discussionmentioning

confidence: 99%

“…Various improved in vitro proteomic approaches [such as affinity chromatography (16)(17)(18)(19)(20)(21), labeled gel electrophoresis in which target proteins are revealed after reduction of protein extract by a TRX͞NADPH thioredoxin reductase (NTR) system (22)(23)(24), or coimmunoprecipitation (25)] suggested Ͼ100 putative TRX targets, but for which further investigations will be required for target validation regarding TRX specificity. Other methods devoted to the large-scale isolation of TRX͞target complexes established in vivo have also been developed, including affinity chromatography of TRX͞target complexes established in vivo during cell culture or the yeast͞mammalian two-hybrid methods (26)(27)(28)(29)(30)(31). However, such in vivo methods have led to the identification of only a few true TRX-interacting proteins.…”

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confidence: 99%

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A yeast two-hybrid knockout strain to explore thioredoxin-interacting proteinsin vivo

Vignols

Bréhélin

Surdin-Kerjan

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

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All organisms contain thioredoxin (TRX), a regulatory thiol:disulfide protein that reduces disulfide bonds in target proteins. Unlike animals and yeast, plants contain numerous TRXs for which no function has been assigned in vivo. Recent in vitro proteomic approaches have opened the way to the identification of >100 TRX putative targets, but of which none of the numerous plant TRXs can be specifically associated. In contrast, in vivo methodologies, including classical yeast two-hybrid (Y2H) systems, failed to reveal the expected high number of TRX targets. Here, we developed a yeast strain named CY306 designed to identify TRX targets in vivo by a Y2H approach. CY306 contains a GAL4 reporter system but also carries deletions of endogenous genes encoding cytosolic TRXs (TRX1 and TRX2) that presumably compete with TRXs introduced as bait. We demonstrate here that, in the CY306 strain, yeast TRX1 and TRX2, as well as Arabidopsis TRX introduced as bait, interact with known TRX targets or putative partners such as yeast peroxiredoxins AHP1 and TSA1, whereas the same interactions cannot be detected in classical Y2H strains. Thanks to CY306, we also show that TRXs interact with the phosphoadenosine-5-phosphosulfate (PAPS) reductase MET16 through a conserved cysteine. Moreover, interactions visualized in CY306 are highly specific depending on the TRX and targets tested. CY306 constitutes a relevant genetic system to explore the TRX interactome in vivo and with high specificity, and opens new perspectives in the search for new TRX-interacting proteins by Y2H library screening in organisms with multiple TRXs. affinity chromatography ͉ gene disruption ͉ thioredoxin targets ͉ two-hybrid system ͉ redox T hioredoxins (TRXs) are small heat-stable oxidoreductases containing two redox-active half-cysteine residues in an active site with a conserved amino acid sequence CXXC (where X indicates various amino acids) (1). TRX was originally identified as hydrogen donor for the reduction of methionine sulfoxide (MetSO) (2) and of sulfate (3) in yeast and received its name when it was characterized as a small protein dithiol hydrogen donor to Escherichia coli ribonucleotide reductase (4). TRX is a hydrogen donor to peroxiredoxins (5) and is also required for a number of metabolic enzymes as part of their catalytic cycle. TRX is implicated in many cellular processes, including protein folding and regulation of transcription factors (6), protein repair after damage by oxidation, sulfur metabolism (7, 8), reduction of dehydroascorbate (9), germination, or reduction of the Calvin cycle and stromal enzymes in plants (10,11).Occurrence of TRXs in all genomes is highly variable and somewhat complex, depending on the organisms concerned. Most organisms, such as E. coli, the yeast Saccharomyces cerevisiae, and mammals (12) contain a limited number of TRX or TRX-like genes (usually fewer than five). In contrast, plants possess numerous TRX isoforms (13,14) or TRX-like proteins (11,(13)(14)(15). During the latest inventories in the Arabidopsis gen...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

A yeast two-hybrid knockout strain to explore thioredoxin-interacting proteinsin vivo

Vignols

Bréhélin

Surdin-Kerjan

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

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“…Two mammalian Trx systems exist: the cytosolic Trx1/TrxR1, and mitochondrial Trx2/TrxR2. A number of proteins have been identified to be redox regulated by Trx and include Nuclear Factor kappa B, (NF-κB), Activator Protein-1 (AP-1), p53, glucocorticoid and estrogen receptors, and HIF1α [84][85][86][87][88][89]. Trx1 is ubiquitously expressed and is upregulated under inflammatory conditions [83].…”

Section: Biochemical and Genetic Regulation Of Reversible Cysteine Oxmentioning

confidence: 99%

Redox-based regulation of signal transduction: Principles, pitfalls, and promises

Janssen–Heininger¹,

Mossman²,

Heintz³

et al. 2008

Free Radical Biology and Medicine

705

652

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“…To study the potential intranuclear effect of Trx on regulation of PPAR␣ transcriptional activity, a possible way is to deliberately in- crease nucleus-localized Trx. Because fluorescent proteins are able to diffuse passively into and out of the nucleus in mammalian cells (Chatterjee and Stochaj, 1998), it could be used to drive Trx into nucleus by fusion of the two proteins, as reported in a previous investigation (Hwang et al, 2004). Therefore, an EYFP-tagged Trx expression vector was transfected into HeLa cells, and its expression and redox function were confirmed by both immunoblotting and insulin-reduction assay (Figure 3, A and B).…”

Section: Down-regulation Of Ppar␣ Transcriptional Activity By Ectopicmentioning

confidence: 99%

“…pcDNA3-Trx(C69/72/79S) was generated by site-directed mutagenesis of pcDNA3-Trx. pEYFP-Trx was constructed by subcloning the Trx cDNA into the EcoRI-BamHI sites of the pEYFP-C1 (Clontech, Palo Alto, CA) according to the literature (Hwang et al, 2004). pCMXmPPAR␣, pCMX-VP16-mPPAR␣, and pCMX-mRXR␣ constructs were kindly provided by Dr. R. M. Evans (Howard Hughes Medical Institute).…”

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confidence: 99%

Thioredoxin-mediated Negative Autoregulation of Peroxisome Proliferator-activated Receptor α Transcriptional Activity

Liu

Shen

2006

MBoC

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PPAR␣, a member of the nuclear receptor superfamily, and thioredoxin, a critical redox-regulator in cells, were found to form a negative feedback loop, which autoregulates transcriptional activity of PPAR␣. Thioredoxin was identified as a target gene of PPAR␣. Activation of PPAR␣ leads to increase of thioredoxin expression as well as its translocation from cytoplasm to nucleus, whereas ectopic overexpression of thioredoxin in the nucleus dramatically inhibited both constitutive and ligand-dependent PPAR␣ activation. As PPAR␣-target genes, the expression of muscle carnitine palmitoyltransferase I, medium chain acyl CoA dehydrogenase, and apolipoprotein A-I were significantly down-regulated by nucleus-targeted thioredoxin at transcriptional or protein level. The suppression of PPAR␣ transcriptional activity by Trx could be enhanced by overexpression of thioredoxin reductase or knockdown of thioredoxin-interacting protein, but abrogated by mutating the redox-active sites of thioredoxin. Mammalian one-hybrid assays showed that thioredoxin inhibited PPAR␣ activity by modulating its AF-1 transactivation domain. It was also demonstrated by electrophoretic mobility-shift assay that thioredoxin inhibited the binding of PPAR␣ to the PPAR-response element. Together, it is speculated that the reported negative-feedback loop may be essential for maintaining the homeostasis of PPAR␣ activity. INTRODUCTIONAs the first identified genetic sensor for fats, PPAR␣ is a ligandactivated transcription factor belonging to the nuclear receptor superfamily. The target genes of PPAR␣ are relatively homogenous group of genes that participate in various aspects of lipid catabolism such as fatty acid uptake through membranes, fatty acid binding in cells, fatty acid oxidation in microsomes, peroxisomes and mitochondria, and lipoprotein assembly and transportation (Lemberger et al., 1996). The significance of PPAR␣ in physiology and disease is evidenced by the fact that it and PPAR␥, another subtype of PPARs, are molecular targets for the lipid-lowering fibrate drugs and insulin-sensitizing thiazolidinedione (TZD), respectively (Evans et al., 2004). Besides activation of PPAR␣ by fatty acid and various exogenous ligands such as fibrates, the regulation of the PPAR␣ transcription activity by coactivators (Dowell et al., 1997), corepressors (Dowell et al., 1999), other transcription factors (TFs; Zhou et al., 1999), and posttranslational modifications including phosphorylation (Juge-Aubry et al., 1999) and ubiquination (Blanquart et al., 2002) have been extensively studied. However, redox regulation of PPAR␣ activity has not been reported so far.Multicellular organisms have evolved complex homeostatic mechanisms to sense and respond to a diverse range of exogenous and endogenous signals. It may be reasonable to expect some mechanisms that rapidly sense and tightly control the activity of PPAR␣ according to metabolic needs under normal physiological condition. Degradation of PPAR␣ by the ubiquitin-proteasome system and decrease of the ubiquitinat...

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Thioredoxin modulates activator protein 1 (AP-1) activity and p27Kip1 degradation through direct interaction with Jab1

Cited by 65 publications

References 41 publications

A yeast two-hybrid knockout strain to explore thioredoxin-interacting proteinsin vivo

A yeast two-hybrid knockout strain to explore thioredoxin-interacting proteinsin vivo

Redox-based regulation of signal transduction: Principles, pitfalls, and promises

Thioredoxin-mediated Negative Autoregulation of Peroxisome Proliferator-activated Receptor α Transcriptional Activity

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