uu.seUppsala University Publications
Change search
ReferencesLink to record
Permanent link

Direct link
The conserved Trp114 residue of thioredoxin reductase 1 has a redox sensor-like function triggering oligomerization and crosslinking upon oxidative stress related to cell death
Show others and affiliations
2015 (English)In: Cell Death and Disease, ISSN 2041-4889, Vol. 6, e1616Article in journal (Refereed) Published
Abstract [en]

The selenoprotein thioredoxin reductase 1 (TrxR1) has several key roles in cellular redox systems and reductive pathways. Here we discovered that an evolutionarily conserved and surface-exposed tryptophan residue of the enzyme (Trp114) is excessively reactive to oxidation and exerts regulatory functions. The results indicate that it serves as an electron relay communicating with the FAD moiety of the enzyme, and, when oxidized, it facilitates oligomerization of TrxR1 into tetramers and higher multimers of dimers. A covalent link can also be formed between two oxidized Trp114 residues of two subunits from two separate TrxR1 dimers, as found both in cell extracts and in a crystal structure of tetrameric TrxR1. Formation of covalently linked TrxR1 subunits became exaggerated in cells on treatment with the pro-oxidant p53-reactivating anticancer compound RITA, in direct correlation with triggering of a cell death that could be prevented by antioxidant treatment. These results collectively suggest that Trp114 of TrxR1 serves a function reminiscent of an irreversible sensor for excessive oxidation, thereby presenting a previously unrecognized level of regulation of TrxR1 function in relation to cellular redox state and cell death induction.

Place, publisher, year, edition, pages
2015. Vol. 6, e1616
National Category
Cell Biology
URN: urn:nbn:se:uu:diva-247175DOI: 10.1038/cddis.2014.574ISI: 000349020500035PubMedID: 25611390OAI: oai:DiVA.org:uu-247175DiVA: diva2:795342
Available from: 2015-03-16 Created: 2015-03-13 Last updated: 2015-03-16Bibliographically approved

Open Access in DiVA

fulltext(2232 kB)73 downloads
File information
File name FULLTEXT01.pdfFile size 2232 kBChecksum SHA-512
Type fulltextMimetype application/pdf

Other links

Publisher's full textPubMed
By organisation
Ludwig Institute for Cancer Research
In the same journal
Cell Death and Disease
Cell Biology

Search outside of DiVA

GoogleGoogle Scholar
Total: 73 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 200 hits
ReferencesLink to record
Permanent link

Direct link