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Title: Dephosphorylation of nucleophosmin by PP1β facilitates pRB binding and consequent E2F1-dependent DNA repair
Authors: Lin, Chiao Yun;Tan, Bertrand Chin-Ming;Liu, Hsuan;Shih, Chii-Jiun;Chien, Kun-Yi;Lin, Chih-Li;Yung, Benjamin Yat-ming
subject: Cell line;DNA damage;DNA repair;Dose-response relationship, radiation;E2F1 transcription factor/genetics;E2F1 transcription factor/metabolism;E2F1 transcription factor/physiology;Gene expression regulation/radiation effects;Mutation, missense/physiology;Nuclear proteins/genetics;Nuclear proteins/metabolism;Nuclear proteins/physiology;Phosphorylation;Protein binding;Protein phosphatase 1/genetics;Protein phosphatase 1/metabolism;Protein phosphatase 1/physiology;Retinoblastoma protein/genetics;Retinoblastoma protein/metabolism;Retinoblastoma protein/physiology;Time factors;Ultraviolet rays/adverse effects
Year: 15-Dec-2010
Publisher: The American Society for Cell Biology
Description: Nucleophosmin (NPM) is an important phosphoprotein with pleiotropic functions in various cellular processes. Although phosphorylation has been postulated as an important functional determinant, possible regulatory roles of this modification on NPM are not fully characterized. Here, we find that NPM is dephosphorylated on various threonine residues (Thr199 and Thr234/237) in response to UV-induced DNA damage. Further experiments indicate that the serine/threonine protein phosphatase PP1β is a physiological NPM phosphatase under both the genotoxic stress and growth conditions. As a consequence, NPM in its hypophosphorylated state facilitates DNA repair. Finally, our results suggest that one possible mechanism of this protective response lies in enhanced NPM-retinoblastoma tumor suppressor protein (pRB) interaction, leading to the relief of the repressive pRB–E2F1 circuitry and the consequent transcriptional activation of E2F1 and several downstream DNA repair genes. Thus, this study unveils a key phosphatase of NPM and highlights a novel mechanism by which the PP1β–NPM pathway contributes to cellular DNA damage response.
Standard no: Molecular Biology of the Cell, 15 Dec. 2010, v. 21, no. 24, p. 4409-4417.
Appears in Collections:Health Technology and Informatics

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