The emerging multiple roles of nuclear Akt

Abstract

Akt is a central player in the signal transduction pathways activated in response to many growth factors, hormones, cytokines, and nutrients and is thought to control a myriad of cellular functions including proliferation and survival, autophagy, metabolism, angiogenesis, motility, and exocytosis. Moreover, dysregulated Akt activity is being implicated in the pathogenesis of a growing number of disorders, including cancer. Evidence accumulated over the past 15 years has highlighted the presence of active Akt in the nucleus, where it acts as a fundamental component of key signaling pathways. For example, nuclear Akt counteracts apoptosis through a block of caspase-activated DNase: deoxyribonuclease and inhibition of chromatin condensation, and is also involved in cell cycle progression control, cell differentiation, mRNA: messenger RNA export, DNA repair, and tumorigenesis. In this review, we shall summarize the most relevant findings about nuclear Akt and its functions.

Therapeutic Innovations for Targeting Hepatoblastoma

“…In the nucleus, active AKT can phosphorylate several intracellular substrates to promote cell survival or DNA repair (129). Furthermore, strong nuclear presence of AKT (S473) has been described in several cancer types, which corroborates the potential role of AKT in the development of drug resistance.…”

Sirt2 Deacetylase Is a Novel AKT Binding Partner Critical for AKT Activation by Insulin

“…Sirt1 was reported to be primarily nuclear, and Sirt2 was reported to be cytoplasmic (16), whereas AKT shuttles to the nucleus following activation (7). To examine whether the effects of insulin and PI3K on AKT binding with Sirt1 and Sirt2 involved changes in their subcellular localization, we analyzed the localization of AKT and the sirtuins in HEK-293T and HeLa cells (Fig.…”

“…PDK1 phosphorylates AKT at Thr 308 and mTORC2 at Ser 473 . A fraction of activated AKT translocates to the nucleus and phosphorylates specific nuclear targets (7). The PI3K-AKT pathway is up-regulated in many cancers, where it promotes cell proliferation, survival, and drug resistance (8).…”

Expression, activation, and role of AKT isoforms in the uterus

“…Furthermore, studies showing a link between nuclear accumulation of AKT and cancer progression have been focused on pan-AKT, without regard to isoform specificity (Martelli et al 2012). Using tissue microarrays, we have recently demonstrated that the nuclei of normal endometrial cell were highly enriched with AKT3, as well as AKT1, albeit at a reduced level; this nuclear enrichment was inverted, with AKT1 being the predominant isoform at the nucleus, upon grade progression of endometrial carcinomas; nuclear localization of AKT was altogether abrogated at a high grade.…”