Acetylation Regulates Thioredoxin Reductase Oligomerization and Activity.
Antioxid Redox Signal
; 29(4): 377-388, 2018 08 01.
Article
em En
| MEDLINE
| ID: mdl-29117711
ABSTRACT
AIMS:
Thioredoxin reductase 1 (TrxR1) is a cancer target and essential selenoprotein that defends the cell against reactive oxygen species and regulates cellular signaling and redox pathways. Previous cell-based studies correlated TrxR1 acetylation with modulated cellular reduction activity, yet the function of specific acetylation sites on TrxR1 remains unknown. INNOVATION We produced site-specifically acetylated TrxR1 variants that also contain selenocysteine (Sec). We demonstrated efficient high-fidelity protein synthesis with 22 different amino acids by simultaneous UAG codon reassignment to NÉ-acetyl-lysine and UGA codon recoding to Sec.RESULTS:
We characterized TrxR1 variants acetylated at physiologically relevant sites and found that single acetylation sites increased TrxR1 activity, enhancing the apparent catalytic rate up to 2.7-fold. The activity increase in acetylated TrxR1 (acTrxR1) is reversible and is reduced following deacetylation with histone deacetylase.CONCLUSION:
Here we present a novel mechanism through which acetylation increases TrxR1 activity by destabilizing low-activity TrxR1 multimers, increasing the population of active dimeric TrxR1. Antioxid. Redox Signal. 29, 377-388.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Tiorredoxina Redutase 1
Limite:
Humans
Idioma:
En
Revista:
Antioxid Redox Signal
Ano de publicação:
2018
Tipo de documento:
Article