Please use this identifier to cite or link to this item: https://hdl.handle.net/11147/2330
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dc.contributor.authorStoner, Christopher S.-
dc.contributor.authorPearson, George D.-
dc.contributor.authorKoç, Ahmet-
dc.contributor.authorMerwin, Jason R.-
dc.contributor.authorLopez, Nathan I.-
dc.contributor.authorMerrill, Gary Frederic-
dc.date.accessioned2016-10-26T08:40:10Z
dc.date.available2016-10-26T08:40:10Z
dc.date.issued2009
dc.identifier.citationStoner, C.S., Pearson, G.D., Koç, A., Merwin, J.R., Lopez, N.I., and Merrill, G.F. (2009). Effect of thioredoxin deletion and p53 cysteine replacement on human p53 activity in wild-type and thioredoxin reductase null yeast. Biochemistry, 48(38), 9156-9169. doi:10.1021/bi900757qen_US
dc.identifier.issn0006-2960
dc.identifier.issn0006-2960-
dc.identifier.urihttp://dx.doi.org/10.1021/bi900757q
dc.identifier.urihttp://hdl.handle.net/11147/2330
dc.description.abstractReporter gene transactivation by human p53 is inhibited in budding yeast lacking the TRR1 gene encoding thioredoxin reductase. To investigate the role of thioredoxin in controlling p53 activity, the level of reporter gene transactivation by p53 was determined in yeast lacking the TRX1 and TRX2 genes encoding cytosolic thioredoxin. Surprisingly, p53 activity was unimpaired in yeast lacking thioredoxin. Subsequent analyses showed that thioredoxin deletion suppressed the inhibitory effect of thioredoxin reductase deletion, suggesting that accumulation of oxidized thioredoxin in mutant yeast was necessary for p53 inhibition. Purified human thioredoxin and p53 interacted in vitro (K d = 0.9 μM thioredoxin). To test the idea that dithio-disulfide exchange reactions between p53 and thioredoxin were responsible for p53 inhibition in mutant yeast, each p53 cysteine was changed to serine, and the effect of the substitution on p53 activity in TRR1 and Δtrr1 yeast was determined. Substitutions at Zn-coordinating cysteines C176, C238, or C242 resulted in p53 inactivation. Unexpectedly, substitution at cysteine C275 also inactivated p53, which was the first evidence for a non-zinc-coordinating cysteine being essential for p53 function. Cysteine substitutions at six positions (C124, C135, C141, C182, C229, and C277) neither inactivated p53 nor relieved the requirement for thioredoxin reductase. Furthermore, no tested combination of these six cysteine substitutions relieved thioredoxin reductase dependence. The results suggested that p53 dependence on thioredoxin reductase either was indirect, perhaps mediated by an upstream activator of p53, or was due to oxidation of one or more of the four essential cysteines.en_US
dc.language.isoenen_US
dc.publisherAmerican Chemical Societyen_US
dc.relation.ispartofBiochemistryen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectProteinsen_US
dc.subjectCysteine substitutionsen_US
dc.subjectDisulfide exchangeen_US
dc.subjectGenes encodingen_US
dc.subjectWild typesen_US
dc.titleEffect of thioredoxin deletion and p53 cysteine replacement on human p53 activity in wild-type and thioredoxin reductase null yeasten_US
dc.typeArticleen_US
dc.authoridTR110769en_US
dc.institutionauthorKoç, Ahmet-
dc.departmentİzmir Institute of Technology. Molecular Biology and Geneticsen_US
dc.identifier.volume48en_US
dc.identifier.issue38en_US
dc.identifier.startpage9156en_US
dc.identifier.endpage9169en_US
dc.identifier.wosWOS:000269892000026en_US
dc.identifier.scopus2-s2.0-70349758334en_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.identifier.doi10.1021/bi900757q-
dc.identifier.pmid19681600en_US
dc.relation.doi10.1021/bi900757qen_US
dc.coverage.doi10.1021/bi900757qen_US
local.message.claim2022-06-06T11:56:50.142+0300|||rp00417|||submit_approve|||dc_contributor_author|||None*
dc.identifier.scopusqualityQ1-
item.openairetypeArticle-
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
item.languageiso639-1en-
item.fulltextWith Fulltext-
item.grantfulltextopen-
item.cerifentitytypePublications-
crisitem.author.dept04.03. Department of Molecular Biology and Genetics-
Appears in Collections:Molecular Biology and Genetics / Moleküler Biyoloji ve Genetik
PubMed İndeksli Yayınlar Koleksiyonu / PubMed Indexed Publications Collection
Scopus İndeksli Yayınlar Koleksiyonu / Scopus Indexed Publications Collection
WoS İndeksli Yayınlar Koleksiyonu / WoS Indexed Publications Collection
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