Inhibition of 14-3-3 binding to Rictor of mTORC2 for Akt phosphorylation at Ser473 is regulated by selenoprotein W

Yeong Ha Jeon, Yong Hwan Park, Joon Hyun Kwon, Jea Hwang Lee, Ick Young Kim

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

14-3-3 reduces cell proliferation by inhibiting the activity of proteins involved in the signaling pathway that includes Akt kinase. Activation of Akt is enhanced by activating the mammalian target of rapamycin complex 2 (mTORC2). 14-3-3 is also a negative regulator of the mTORC2/Akt pathway, by interacting with a component of mTORC2. Recently, we reported that selenoprotein W (SelW) regulated the interaction between 14-3-3 and its target protein, CDC25B. Here, we show that the binding of Rictor, a component of mTORC2, to 14-3-3, is regulated by the interaction of 14-3-3 with SelW. When SelW was down-regulated, mTORC2-dependent phosphorylation of Akt at Ser473 was decreased. However, the phosphorylation of Thr308 was not affected. The interaction of Rictor with 14-3-3 was increased in SelW-knockdown cells, as compared to control cells. SelW-knockdown cells were also more sensitive to DNA damage induced by etoposide, than control cells. This phenomenon was due to the decreased phosphorylation of Akt at Ser473. We also found that ectopic expression of SelW(U13C) reduced the interaction between Rictor and 14-3-3, leading to Akt phosphorylation at Ser473. Taken together, these findings demonstrate that SelW activates the mTORC2/Akt pathway for Akt phosphorylation at Ser473, by interrupting the binding of Rictor to 14-3-3.

Original languageEnglish
Pages (from-to)2135-2142
Number of pages8
JournalBiochimica et Biophysica Acta - Molecular Cell Research
Volume1833
Issue number10
DOIs
Publication statusPublished - 2013 Oct 1

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Selenoprotein W
Phosphorylation
Etoposide
TOR complex 2
DNA Damage
Proteins
Phosphotransferases
Cell Proliferation

Keywords

  • 14-3-3
  • Akt
  • MTOR
  • Rictor
  • Selenoprotein W

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Inhibition of 14-3-3 binding to Rictor of mTORC2 for Akt phosphorylation at Ser473 is regulated by selenoprotein W. / Jeon, Yeong Ha; Park, Yong Hwan; Kwon, Joon Hyun; Lee, Jea Hwang; Kim, Ick Young.

In: Biochimica et Biophysica Acta - Molecular Cell Research, Vol. 1833, No. 10, 01.10.2013, p. 2135-2142.

Research output: Contribution to journalArticle

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