UCL Discovery Stage
UCL home » Library Services » Electronic resources » UCL Discovery Stage

Polyphosphate degradation by Nudt3-Zn²⁺ mediates oxidative stress response

Samper-Martín, B; Sarrias, A; Lázaro, B; Pérez-Montero, M; Rodríguez-Rodríguez, R; Ribeiro, MPC; Bañón, A; ... Bru, S; + view all (2021) Polyphosphate degradation by Nudt3-Zn²⁺ mediates oxidative stress response. Cell Reports , 37 (7) , Article 110004. 10.1016/j.celrep.2021.110004. Green open access

[thumbnail of Saiardi_1-s2.0-S2211124721014820-main.pdf]
Preview
Text
Saiardi_1-s2.0-S2211124721014820-main.pdf - Published Version

Download (4MB) | Preview

Abstract

Polyphosphate (polyP) is a polymer of hundreds of phosphate residues present in all organisms. In mammals, polyP is involved in crucial physiological processes, including coagulation, inflammation, and stress response. However, after decades of research, the metabolic enzymes are still unknown. Here, we purify and identify Nudt3, a NUDIX family member, as the enzyme responsible for polyP phosphatase activity in mammalian cells. We show that Nudt3 shifts its substrate specificity depending on the cation; specifically, Nudt3 is active on polyP when Zn2+ is present. Nudt3 has in vivo polyP phosphatase activity in human cells, and importantly, we show that cells with altered polyP levels by modifying Nudt3 protein amount present reduced viability upon oxidative stress and increased DNA damage, suggesting that polyP and Nudt3 play a role in oxidative stress protection. Finally, we show that Nudt3 is involved in the early stages of embryo development in zebrafish.

Type: Article
Title: Polyphosphate degradation by Nudt3-Zn²⁺ mediates oxidative stress response
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.celrep.2021.110004
Publisher version: https://doi.org/10.1016/j.celrep.2021.110004
Language: English
Additional information: Copyright © 2021 The Author(s). This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Keywords: DNA damage, NUDIX, Nudt3, mammalian polyphosphatase, oxidative stress, polyphosphate
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Lab for Molecular Cell Bio MRC-UCL
URI: https://discovery-pp.ucl.ac.uk/id/eprint/10139010
Downloads since deposit
1,152Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item