A novel activation-induced suicidal degradation mechanism for Akt by selenium

Ji Hyun Lee, Sun Hye Shin, Seongman Kang, Yun Sil Lee, Sangwoo Bae

Research output: Contribution to journalArticlepeer-review

23 Scopus citations


Selenium has been associated with an anti-cancer effect via the modulation of Akt. In order to investigate whether selenium modulates Akt by hitherto unidentified molecular mechanisms, we examined the effect of selenium on the stability and activity of Akt. Selenium induced destabilization of Akt which is coupled to its own enzyme activation. Mutation of T308 and S473 of Akt to alanine as well as the inhibition or depletion of upstream kinases for Akt activation blocked Akt degradation. These features of Akt degradation are reminiscent of the activation-induced suicidal degradation' mechanism. PTEN was also required for Akt destabilization as Akt activation alone was unable to elicit Akt degradation in the absence of PTEN. Conversely, PTEN introduction in PTEN-null prostate cancer cells restored the ability to degrade Akt upon selenium treatment. Collectively, selenium seems to achieve ultimate negative regulation of Akt signaling by destabilizing the protein, and this regulation mechanism might provide a paradigm for the anti-cancer activity of selenium.

Original languageEnglish
Pages (from-to)91-97
Number of pages7
JournalInternational Journal of Molecular Medicine
Issue number1
StatePublished - Jan 2008


  • Activation-induced degradation
  • Akt
  • Anti-cancer
  • PTEN
  • Selenium


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