Compensatory Protection of Thioredoxin-Deficient Cells from Etoposide-Induced Cell Death by Selenoprotein W via Interaction with 14-3-3
Autor: | Yeong Ha Jeon, Hyunwoo Kang, Minju Ham, Kwan Young Ko, Ick Young Kim |
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Rok vydání: | 2021 |
Předmět: |
Programmed cell death
QH301-705.5 Poly ADP ribose polymerase Population Poly (ADP-Ribose) Polymerase-1 Cleavage (embryo) Catalysis Article Cell Line Inorganic Chemistry chemistry.chemical_compound Mice Thioredoxins Cell Line Tumor Animals Humans Physical and Theoretical Chemistry Biology (General) Phosphorylation education Molecular Biology Protein kinase B QD1-999 Spectroscopy 14-3-3 Etoposide education.field_of_study Selenocysteine Cell Death Chemistry Akt Organic Chemistry General Medicine Selenoprotein W thioredoxin Computer Science Applications Cell biology HEK293 Cells 14-3-3 Proteins MCF-7 Cells Thioredoxin Oxidation-Reduction Protein Binding Signal Transduction |
Zdroj: | International Journal of Molecular Sciences International Journal of Molecular Sciences, Vol 22, Iss 10338, p 10338 (2021) Volume 22 Issue 19 |
ISSN: | 1422-0067 |
Popis: | Selenoprotein W (SELENOW) is a 9.6 kDa protein containing selenocysteine (Sec, U) in a conserved Cys-X-X-Sec (CXXU) motif. Previously, we reported that SELENOW regulates various cellular processes by interacting with 14-3-3β at the U of the CXXU motif. Thioredoxin (Trx) is a small protein that plays a key role in the cellular redox regulatory system. The CXXC motif of Trx is critical for redox regulation. Recently, an interaction between Trx1 and 14-3-3 has been predicted. However, the binding mechanism and its biological effects remain unknown. In this study, we found that Trx1 interacted with 14-3-3β at the Cys32 residue in the CXXC motif, and SELENOW and Trx1 were bound at Cys191 residue of 14-3-3β. In vitro binding assays showed that SELENOW and Trx1 competed for interaction with 14-3-3β. Compared to control cells, Trx1-deficient cells and SELENOW-deficient cells showed increased levels of both the subG1 population and poly (ADP-ribose) polymerase (PARP) cleavage by etoposide treatment. Moreover, Akt phosphorylation of Ser473 was reduced in Trx1-deficient cells and was recovered by overexpression of SELENOW. These results indicate that SELENOW can protect Trx1-deficient cells from etoposide-induced cell death through its interaction with 14-3-3β. |
Databáze: | OpenAIRE |
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