The emerging multiple roles of nuclear Akt
Alberto M. Martelli,Alberto M. Martelli,Giovanna Tabellini,Daniela Bressanin,Andrea Ognibene,Kaoru Goto,Lucio Cocco,Camilla Evangelisti +7 more
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TLDR
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, and the most relevant findings about nuclear Akt are summarized.About:
This article is published in Biochimica et Biophysica Acta.The article was published on 2012-12-01 and is currently open access. It has received 181 citations till now. The article focuses on the topics: PI3K/AKT/mTOR pathway & Protein kinase B.read more
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Akt inhibitors in cancer treatment: The long journey from drug discovery to clinical use (Review)
George Mihai Nitulescu,Denisa Margina,Petras Juzenas,Qian Peng,Octavian Tudorel Olaru,Emmanouil Saloustros,Concettina Fenga,Demetrios Α. Spandidos,Massimo Libra,Aristidis Tsatsakis +9 more
TL;DR: The pipeline of Akt inhibitors and their preclinical and clinical examination status are explored, presenting the potential clinical application of these agents as a monotherapy or in combination with ionizing radiation, other targeted therapies, or chemotherapy.
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PI3K-AKT-mTOR inhibition in cancer immunotherapy, redux.
TL;DR: This review discusses how PI3K-AKT-mTOR inhibitors target cancer cell biology, attenuate immune cell effector function and modulate the tumor microenvironment, and how the immunomodulatory potential of these inhibitors can be exploited through rational combinations with immunotherapies and targeted therapies.
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5-Fluorouracil resistance mechanisms in colorectal cancer: From classical pathways to promising processes
Sabrina Blondy,Valentin David,Mireille Verdier,Muriel Mathonnet,Aurélie Perraud,Niki Christou +5 more
TL;DR: A global outline of different mechanisms from disruption of 5‐FU‐metabolic enzymes and classic cellular processes to drug transporters and epithelial‐mesenchymal transition induction is constructed, directed to tumor microenvironment function as well as epigenetic alterations and miRNA dysregulation.
Journal ArticleDOI
Signaling Specificity in the Akt Pathway in Biology and Disease
Alex Toker,Sandra Marmiroli +1 more
TL;DR: This work summarizes the view of how Akt selectivity is achieved in the context of subcellular localization, isoform-specific substrate phosphorylation and context-dependent functions in normal and pathophysiological settings.
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PD-L1 promotes OCT4 and Nanog expression in breast cancer stem cells by sustaining PI3K/AKT pathway activation.
Sheema Almozyan,Dilek Colak,Fatmah A. Mansour,Ayodele Alaiya,Olfat Al-Harazi,Amal Qattan,Falah Al-Mohanna,Monther Al-Alwan,Hazem Ghebeh +8 more
TL;DR: A novel role for PD‐L1 in sustaining stemness of breast cancer cells is demonstrated and the subpopulation and its associated molecular pathways that would be targeted upon anti‐PD‐ L1 therapy are identified.
References
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Akt Promotes Cell Survival by Phosphorylating and Inhibiting a Forkhead Transcription Factor
Anne Brunet,Azad Bonni,Michael J. Zigmond,Michael Z. Lin,Peter Juo,Linda Hu,Michael J. Anderson,Karen C. Arden,John Blenis,Michael E. Greenberg +9 more
TL;DR: It is demonstrated that Akt also regulates the activity of FKHRL1, a member of the Forkhead family of transcription factors, which triggers apoptosis most likely by inducing the expression of genes that are critical for cell death, such as the Fas ligand gene.
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Akt Phosphorylation of BAD Couples Survival Signals to the Cell-Intrinsic Death Machinery
Sandeep Robert Datta,Henryk Dudek,Xu Tao,Shane C. Masters,Haian Fu,Yukiko Gotoh,Michael E. Greenberg +6 more
TL;DR: It is shown that growth factor activation of the PI3'K/Akt signaling pathway culminates in the phosphorylation of the BCL-2 family member BAD, thereby suppressing apoptosis and promoting cell survival.
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AKT/PKB signaling: navigating downstream.
TL;DR: Those Akt substrates that are most likely to contribute to the diverse cellular roles of Akt, which include cell survival, growth, proliferation, angiogenesis, metabolism, and migration are discussed.
Journal ArticleDOI
mTOR: from growth signal integration to cancer, diabetes and ageing
TL;DR: Mammalian TOR complex 1 (mTORC1) and mTORC2 exert their actions by regulating other important kinases, such as S6 kinase (S6K) and Akt.
Journal ArticleDOI
Glycogen synthase kinase-3β regulates cyclin D1 proteolysis and subcellular localization
TL;DR: It is demonstrated that glycogen synthase kinase-3beta (GSK-3 beta) phosphorylates cyclin D1 specifically on Thr-286, thereby triggering rapid cyclinD1 turnover, which leads to proteasomal degradation of D1 and linked to phosphorylation and proteolytic turnover of cyclin L1 and its subcellular localization during the cell division cycle.
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