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The mTOR signaling pathways regulate cell growth and are involved in multiple human diseases. Here, we identify UBTOR, a previously unannotated gene as a functional player in regulating cell growth and mTOR signaling. Reduction of UBTOR function in cultured hippocampal neurons and PC12 cells promotes neurite outgrowth. UBTOR depletion activates mTOR signaling and promotes cell growth, whilst UBTOR overexpression suppresses colony formation in cancer cell lines. Studies in cultured cells and zebrafish model show that UBTOR inhibits mTOR signaling by stabilizing the mTOR complex component DEPTOR, and ubtor gene disruption result in higher mTOR activity and aggravate HRAS(G12V) induced neoplasia in the zebrafish. Lastly, UBTOR depletion promotes tumor growth and mTOR signaling in a xenograft mouse model. Together, our results demonstrate how UBTOR regulates cell growth and neoplasia via mTOR signaling.
This article was published in the following journal.
Name: PLoS genetics
Rivastigmine (Riv) is a potent and selective cholinesterase (acetylcholinesterase, AChE and butyrylcholinesterase, BuChE) inhibitor developed for the treatment of Alzheimer's disease (AD). To elucidat...
We investigated the role of the p38 mitogen-activated protein kinase (MAPK) pathway in electrical stimulation-induced neurite outgrowth of PC12 mutant cells in which nerve growth factor (NGF)-induced ...
Traumatic spinal cord injury is a common and severe complication after an accident. As we all know that neurite outgrowth of neurons is difficult after a spinal cord injury. Endosome system is associa...
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This phase II trial studies how well PI3K/mTOR inhibitor LY3023414 works in treating patients with solid tumors, non-Hodgkin lymphoma, or histiocytic disorders with TSC or PI3K/MTOR mutati...
The present primary therapy of cervical intraepithelial neoplasia (CIN) grade 3 and persistent CIN 2 represents conisation. Surgical treatment can cause perioperative (infection, bleeding ...
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Myelin proteins that are expressed as three isoforms: Nogo-A, Nogo-B, and Nogo-C. These share a C-terminal reticulon homology domain (RHD), consisting of two hydrophobic membrane domains flanking a 66 amino acid (Nogo-66) hydrophilic region. A long transmembrane region allows conformations that either span the entire membrane or fold into a hairpin conformation. Nogo inhibits NEURITE outgrowth and modulates wiring and the restriction of SYNAPTIC PLASTICITY in the adult central nervous system. It also regulates neurite fasciculation, branching, and extension in the developing nervous system.
An adaptor protein, consisting of seven WD REPEATS along its length, that functions as a component of the MECHANISTIC TARGET OF RAPAMYCIN COMPLEX 1 and MTORC2 COMPLEX. It interacts directly with MTOR to enhance its kinase activity and stabilizes the MTOR-RPTOR PROTEIN interaction in nutrient-poor conditions, favoring RPTOR inhibition of MTOR activity.
Process of organizing neighboring AXONS into a bundle or a fascicle during neurite outgrowth mediated by CELL ADHESION MOLECULES.
A multiprotein complex consisting of MTOR KINASE; MLST8 PROTEIN; rapamycin-insensitive companion of mTOR protein (RICTOR PROTEIN); and PRR5 (proline-rich protein 5). Like MTORC1, it also regulates cell growth and proliferation in response to growth factors but may not be as sensitive to nutrient availability and is insensitive to SIROLIMUS. In contrast to MTORC1, it can regulate the ACTIN CYTOSKELETON through RHO GTPASES to promote the formation of STRESS FIBERS. The mTORC2 complex also plays a critical role in AKT1 PROTEIN KINASE phosphorylation and activation.
A nervous tissue specific protein which is highly expressed in NEURONS during development and NERVE REGENERATION. It has been implicated in neurite outgrowth, long-term potentiation, SIGNAL TRANSDUCTION, and NEUROTRANSMITTER release. (From Neurotoxicology 1994;15(1):41-7) It is also a substrate of PROTEIN KINASE C.
Bioinformatics is the application of computer software and hardware to the management of biological data to create useful information. Computers are used to gather, store, analyze and integrate biological and genetic information which can then be applied...
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