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Huma Multiple Myeloma Cell line, AMO1, treated with NCP26, LC-MSMS analysis

ABSTRACT: The human multiple myeloma cell line, AMO1, was treated with NCP26, an ATP-competitive EPRS inhibitor, and a total proteome-wide analysis was performed to determine the effect of NCP26 treatment on protein dynamics.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Plasma Cell, Multiple Myeloma Cell Line

DISEASE(S): Multiple Myeloma

SUBMITTER: Keiji Kurata

LAB HEAD: Kenneth Carl Anderson

PROVIDER: PXD029453 | Pride | 2023-03-11

REPOSITORIES: Pride

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Publications

Prolyl-tRNA synthetase as a novel therapeutic target in multiple myeloma.

Kurata Keiji K James-Bott Anna A Tye Mark A MA Yamamoto Leona L Samur Mehmet K MK Tai Yu-Tzu YT Dunford James J Johansson Catrine C Senbabaoglu Filiz F Philpott Martin M Palmer Charlotte C Ramasamy Karthik K Gooding Sarah S Smilova Mihaela M Gaeta Giorgia G Guo Manman M Christianson John C JC Payne N Connor NC Singh Kritika K Karagoz Kubra K Stokes Matthew E ME Ortiz Maria M Hagner Patrick P Thakurta Anjan A Cribbs Adam A Mazitschek Ralph R Hideshima Teru T Anderson Kenneth C KC Oppermann Udo U

Blood cancer journal 20230112 1

Multiple myeloma (MM) is a plasma cell malignancy characterised by aberrant production of immunoglobulins requiring survival mechanisms to adapt to proteotoxic stress. We here show that glutamyl-prolyl-tRNA synthetase (GluProRS) inhibition constitutes a novel therapeutic target. Genomic data suggest that GluProRS promotes disease progression and is associated with poor prognosis, while downregulation in MM cells triggers apoptosis. We developed NCP26, a novel ATP-competitive ProRS inhibitor that ...[more]

PMID: 36631435

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Project description:The sympathetic nervous system innervates peripheral organs to regulate their function and maintain homeostasis, whereas target cells also produce neurotrophic factors to promote sympathetic innervation1,2. The molecular basis of this bi-directional communication is unknown. Here we use thermogenic adipose tissue from mice as a model system to show that T cells, specifically T cells, have a crucial role in promoting sympathetic innervation, at least in part by driving the expression of TGF1 in parenchymal cells via the IL-17 receptor complex (IL-17RC). Ablation of IL-17RC specifically in adipose tissue reduces expression of TGF1 in adipocytes, impairs local sympathetic innervation and causes obesity and other metabolic phenotypes that are consistent with defective thermogenesis; innervation can be fully rescued by restoring TGF1 expression. Ablating cells and the IL-17RC signalling pathway also impairs sympathetic innervation in salivary glands and the lungs. These findings demonstrate coordination between T cells and parenchymal cells to regulate sympathetic innervation.

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Proteomic analysis of whole brains from Ndufs4-/- mice treated with doxycycline

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2021-09-09 | PXD022860 | Pride

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2023-06-09 | PXD041952 | Pride

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2019-09-30 | PXD012285 | Pride

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