Dephosphorylation of Nucleophosmin by PP1β Facilitates pRB Binding and Consequent E2F1-dependent DNA Repair

• DOI: 10.1091/mbc.e10-03-0239
• Publication Date: 2010-10-21T03:03:22Z
• Authors: Chiao Yun Lin; Bertrand Chin-Min...; Hsuan Liu; Chii-Jiun Shih; Kun-Yi Chien; Chih-Li Lin; Benjamin Yat-Ming...
• Keywords: Nucleophosmin; Hyperphosphorylation; E2F1; Retinoblastoma protein; Dephosphorylation; E2F; DNA-PKcs

Nucleophosmin (NPM) is an important phosphoprotein with pleiotropic functions in various cellular processes. Although phosphorylation has been postulated as functional determinant, possible regulatory roles of this modification on NPM are not fully characterized. Here, we find that dephosphorylated threonine residues (Thr199 and Thr234/237) response to UV-induced DNA damage. Further experiments indicate the serine/threonine protein phosphatase PP1β a physiological under both genotoxic stress growth conditions. As consequence, its hypophosphorylated state facilitates repair. Finally, our results suggest one mechanism protective lies enhanced NPM-retinoblastoma tumor suppressor (pRB) interaction, leading relief repressive pRB–E2F1 circuitry consequent transcriptional activation E2F1 several downstream repair genes. Thus, study unveils key highlights novel by which PP1β–NPM pathway contributes damage response.