The Akt DUBbed InAktive

Kui Lin^*

Department of Translational Oncology, Research Oncology, Genentech, 1 DNA Way, South San Francisco, CA 94080, USA.

Abstract: Akt is a central node in the phosphoinositide-3 kinase–Akt–mammalian target of rapamycin pathway and is activated by a multistep process in response to growth factor stimulation. An additional layer of posttranslational modification has emerged as a new paradigm in the regulation of Akt. The identification of an E3 ligase for Lys⁶³-linked ubiquitination of Akt has now been complemented with the discovery of the tumor suppressor cylindromatosis as a deubiquitinating enzyme (DUB) for Akt. Thus, like phosphorylation and dephosphorylation, cycles of ubiquitination and deubiquitination provide additional on-off switches that keep Akt activity in balance, and disturbances in this balance have pathological consequences.

*Corresponding author. E-mail, klin{at}gene.com

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