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2016 •
Emergence of survival strategies is a key step for organisms during evolution. The capacity to adapt from nutrient-rich to nutrient-poor environments led to the appearance of protein complexes regulating anabolic and catabolic pathways. The evolutionarily conserved kinase mTOR (mechanistic target of rapamycin) emerged as a crucial and central protein for regulating many different cellular functions in response to environmental changes. The kinase mTOR interacts with different partners to form two distinct complexes, which differentiate from one to the other by the presence of the regulatory-associated protein of mTOR (raptor) in the mTORC1 and the rapamycininsensitive companion of mTOR (rictor) in the mTORC2. These two mTOR complexes integrate intracellular and extracellular signals, such as presence of growth factors or amino acids, energy status, oxygen and stress, which lead to modulation of mTORC1/2-dependent signaling events. The mTORC1 regulates key cellular pathways like prot...
Cell death discovery
Caspase-mediated cleavage of raptor participates in the inactivation of mTORC1 during cell death2016 •
The mammalian target of rapamycin complex 1 (mTORC1) is a highly conserved protein complex regulating key pathways in cell growth. Hyperactivation of mTORC1 is implicated in numerous cancers, thus making it a potential broad-spectrum chemotherapeutic target. Here, we characterized how mTORC1 responds to cell death induced by various anticancer drugs such rapamycin, etoposide, cisplatin, curcumin, staurosporine and Fas ligand. All treatments induced cleavage in the mTORC1 component, raptor, resulting in decreased raptor-mTOR interaction and subsequent inhibition of the mTORC1-mediated phosphorylation of downstream substrates (S6K and 4E-BP1). The cleavage was primarily mediated by caspase-6 and occurred at two sites. Mutagenesis at one of these sites, conferred resistance to cell death, indicating that raptor cleavage is important in chemotherapeutic apoptosis.
Molecular Biology International
mTOR Signaling in Protein Translation Regulation: Implications in Cancer Genesis and Therapeutic Interventions2014 •
mTOR is a central nutrient sensor that signals a cell to grow and proliferate. Through distinct protein complexes it regulates different levels of available cellular energy substrates required for cell growth. One of the important functions of the complex is to maintain available amino acid pool by regulating protein translation. Dysregulation of mTOR pathway leads to aberrant protein translation which manifests into various pathological states. Our review focuses on the role mTOR signaling plays in protein translation and its physiological role. It also throws some light on available data that show translation dysregulation as a cause of pathological complexities like cancer and the available drugs that target the pathway for cancer treatment.
2010 •
The apoptotic mode of cell death (programmed cell death) is an active and defined process that plays an important role in the development of multicellular organisms and in the regulation and maintenance of cell populations in tissues under physiologic and pathologic conditions. Since dysregulation of apoptosis is associated with the progress of many diseases, induction of apoptosis is an interesting pharmacological target for the therapy of many diseases. Our study shows that the novel semisynthetic pentacyclic triterpenoid C-KβBA has a profound antiproliferative effect on different tumor cell lines and that it induces apoptosis of tumor cells in vitro and vivo. Previous studies have shown that the mammalian target of rapamycin (mTOR) is a key regulator for many cells activities, and that the perturbation of this signaling pathway is implicated in many diseases and metabolic disorders. Accordingly targeting the mTOR signaling pathway seems to be a promising therapeutic approach for ...
Cell Death and Differentiation
Cell size reduction induced by inhibition of the mTOR/S6K-signaling pathway protects Jurkat cells from apoptosis2005 •
Progress in Neurobiology
Shedding new light on neurodegenerative diseases through the mammalian target of rapamycin2012 •
Pharmaceutics
Inhibitors of the PI3K/Akt/mTOR Pathway in Prostate Cancer Chemoprevention and Intervention2021 •
The phosphatidylinositol 3-kinase (PI3K)/serine-threonine kinase (Akt)/mammalian target of the rapamycin (mTOR)-signaling pathway has been suggested to have connections with the malignant transformation, growth, proliferation, and metastasis of various cancers and solid tumors. Relevant connections between the PI3K/Akt/mTOR pathway, cell survival, and prostate cancer (PC) provide a great therapeutic target for PC prevention or treatment. Recent studies have focused on small-molecule mTOR inhibitors or their usage in coordination with other therapeutics for PC treatment that are currently undergoing clinical testing. In this study, the function of the PI3K/Akt/mTOR pathway, the consequence of its dysregulation, and the development of mTOR inhibitors, either as an individual substance or in combination with other agents, and their clinical implications are discussed. The rationale for targeting the PI3K/Akt/mTOR pathway, and specifically the application and potential utility of natura...
Journal of Clinical Investigation
MTORC1 regulates cardiac function and myocyte survival through 4E-BP1 inhibition in mice2010 •
International Journal of Molecular Sciences
Chemical Inhibitors and microRNAs (miRNA) Targeting the Mammalian Target of Rapamycin (mTOR) Pathway: Potential for Novel Anticancer Therapeutics2013 •
Current Protein & Peptide Science
The Complexes of Mammalian Target of Rapamycin2010 •
2011 •
2015 •
2014 •
2010 •
Proceedings of the National Academy of Sciences
Reactive nitrogen species regulate autophagy through ATM-AMPK-TSC2-mediated suppression of mTORC12013 •
2015 •
Journal of Proteome Research
mTor Is a Signaling Hub in Cell Survival: A Mass-Spectrometry-Based Proteomics Investigation2014 •
International Journal of Molecular Sciences
mTOR Inhibitors in Advanced Biliary Tract CancersScientific reports
Streptomyces sp metabolite(s) promotes Bax mediated intrinsic apoptosis and autophagy involving inhibition of mTOR pathway in cervical cancer cell lines2018 •
Biochemical Pharmacology
Fisetin inhibits human melanoma cell growth through direct binding to p70S6K and mTOR: Findings from 3-D melanoma skin equivalents and computational modeling2014 •
2011 •
Carcinogenesis
Dihydroartemisinin inhibits the mammalian target of rapamycin-mediated signaling pathways in tumor cells2014 •
Journal of Neurochemistry
Is the mTOR-signalling cascade disrupted in Schizophrenia?2014 •
Critical Reviews™ in Eukaryotic Gene Expression
mTOR Signaling in Cancer Cell Motility and Tumor Metastasis2010 •
2010 •
Cancer Biology & Therapy
Rapamycins: Mechanisms of Action and Cellular Resistance2003 •
2012 •
Trends in Neurosciences
mTOR signaling: At the crossroads of plasticity, memory and disease2010 •
Molecular cancer therapeutics
Mammalian target of rapamycin inhibition as a therapeutic strategy in the management of urologic malignancies2008 •
Biochemical Journal
Regulation and function of ribosomal protein S6 kinase (S6K) within mTOR signalling networks2012 •
F1000 - Post-publication peer review of the biomedical literature
Faculty of 1000 evaluation for mTOR kinase structure, mechanism and regulation2013 •
Oxidative medicine and cellular longevity
Mammalian target of rapamycin: hitting the bull's-eye for neurological disordersMicrobiology and molecular …
Signaling by Target of Rapamycin Proteins In Cell Growth Control2005 •