Compensatory Protection of Thioredoxin-Deficient Cells from Etoposide-Induced Cell Death by Selenoprotein W via Interaction with 14-3-3
- Authors
- Kang, Hyunwoo; Jeon, Yeong Ha; Ham, Minju; Ko, Kwanyoung; Kim, Ick Young
- Issue Date
- 10월-2021
- Publisher
- MDPI
- Keywords
- 14-3-3; Akt; cell death; selenoprotein W; thioredoxin
- Citation
- INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v.22, no.19
- Indexed
- SCIE
SCOPUS
- Journal Title
- INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
- Volume
- 22
- Number
- 19
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/136158
- DOI
- 10.3390/ijms221910338
- ISSN
- 1661-6596
- Abstract
- 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 14-3-3 beta 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 14-3-3 beta at the Cys32 residue in the CXXC motif, and SELENOW and Trx1 were bound at Cys191 residue of 14-3-3 beta. In vitro binding assays showed that SELENOW and Trx1 competed for interaction with 14-3-3 beta. 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 14-3-3 beta.
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