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- W2901553675 abstract "To fight resistances to radiotherapy, the understanding of escape mechanisms of tumor cells is crucial. The aim of this study was to identify phosphoproteins that are regulated upon irradiation. The comparative analysis of the phosphoproteome before and after irradiation brought nucleophosmin (NPM1) into focus as a versatile phosphoprotein that has already been associated with tumorigenesis. We could show that knockdown of NPM1 significantly reduces tumor cell survival after irradiation. NPM1 is dephosphorylated stepwise within 1 hour after irradiation at two of its major phosphorylation sites: threonine-199 and threonine-234/237. This dephosphorylation is not the result of a fast cell cycle arrest, and we found a heterogenous intracellular distribution of NPM1 between the nucleoli, the nucleoplasm, and the cytoplasm after irradiation. We hypothesize that the dephosphorylation of NPM1 at threonine-199 and threonine-234/237 is part of the immediate response to irradiation and of importance for tumor cell survival. These findings could make NPM1 an attractive pharmaceutical target to radiosensitize tumor cells and improve the outcome of radiotherapy by inhibiting the pathways that help tumor cells to escape cell death after gamma irradiation." @default.
- W2901553675 created "2018-11-29" @default.
- W2901553675 creator A5021127370 @default.
- W2901553675 creator A5021129753 @default.
- W2901553675 creator A5040088384 @default.
- W2901553675 creator A5066286640 @default.
- W2901553675 date "2019-02-01" @default.
- W2901553675 modified "2023-09-30" @default.
- W2901553675 title "Phosphoproteome Profiling Reveals Multifunctional Protein NPM1 as part of the Irradiation Response of Tumor Cells" @default.
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- W2901553675 doi "https://doi.org/10.1016/j.tranon.2018.10.015" @default.
- W2901553675 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6240713" @default.
- W2901553675 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30453269" @default.
- W2901553675 hasPublicationYear "2019" @default.
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