Research ArticleCell Biology

Cycles of Ubiquitination and Deubiquitination Critically Regulate Growth Factor–Mediated Activation of Akt Signaling

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Sci. Signal.  08 Jan 2013:
Vol. 6, Issue 257, pp. ra3
DOI: 10.1126/scisignal.2003197

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DUBbing Akt

Growth factors trigger the ubiquitination of the kinase Akt, which facilitates its activation. Yang et al. identified the tumor suppressor CYLD as a deubiquitinase (DUB) that inhibits Akt activity. CYLD associated with Akt under nutrient-deficient conditions and dissociated from Akt after growth factor stimulation. Compared to prostate cancer cells with CYLD, those that were deficient in CYLD showed increased glucose uptake and proliferation, processes that are enhanced by Akt activity, and developed into larger tumors when injected into mice. In individuals with primary prostate tumors, decreased abundance of CYLD correlated with increased activation of Akt. Thus, deubiquitination of Akt is required to reset its activity, and attenuation of Akt may contribute to the tumor-suppressive function of CYLD.