Compensatory protection of thioredoxin-deficient cells from etoposide-induced cell death by selenoprotein w via interaction with 14-3-3

Hyunwoo Kang, Yeong Ha Jeon, Minju Ham, Kwanyoung Ko, Ick Young Kim

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)


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 (ADPribose) 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.

Original languageEnglish
Article number338
JournalInternational journal of molecular sciences
Issue number19
Publication statusPublished - 2021 Oct 1

Bibliographical note

Funding Information:
Funding: This work was supported by the National Research Foundation of Korea (NRF) grant by the Korea government (MSIP) (NRF-2019R1A2B5B01069901) and by the Korea University Grant.

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.


  • 14-3-3
  • Akt
  • Cell death
  • Selenoprotein W
  • Thioredoxin

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry


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