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

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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.
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Document Type: Research Article

Affiliations: Laboratory of Modulation of Radiobiological Responses, Korea Institute of Radiological and Medical Sciences, Seoul 139-706, Korea

Publication date: January 1, 2008

More about this publication?
  • The International Journal of Molecular Medicine is a monthly, peer-reviewed journal devoted to the publication of high quality studies related to the molecular mechanisms of human disease. The journal welcomes research on all aspects of molecular and clinical research, ranging from biochemistry to immunology, pathology, genetics, human genomics, microbiology, molecular pathogenesis, molecular cardiology, molecular surgery and molecular psychology.

    The International Journal of Molecular Medicine aims to provide an insight for researchers within the community in regard to developing molecular tools and identifying molecular targets for the diagnosis and treatment of a diverse number of human diseases.
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