title: The Akt DUBbed InAktive.
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 Lys(63)-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.
authors.affiliation: Department of Translational Oncology, Research Oncology, Genentech, 1 DNA Way, South San Francisco, CA 94080, USA. klin@gene.com
authors.forename: Kui
authors.initials: K
authors.lastname: Lin
mesh_terms: D000074749:Deubiquitinating Enzyme CYLD; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008954:Models, Biological; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D025521:Tumor Suppressor Proteins / Q000378:metabolism*; D054875:Ubiquitination / Q000502:physiology*
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D025521:Tumor Suppressor Proteins; D051057:Proto-Oncogene Proteins c-akt; C409984:CYLD protein, human; D000074749:Deubiquitinating Enzyme CYLD