Polyphosphate degradation by Nudt3-Zn 2+ mediates oxidative stress response
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- dc.contributor.author Samper-Martín, Bàrbara
- dc.contributor.author Sarrias, Ana
- dc.contributor.author Lázaro, Blanca
- dc.contributor.author Pérez-Montero, Marta
- dc.contributor.author Rodríguez-Rodríguez, Rosalía
- dc.contributor.author Ribeiro, Mariana P.C.
- dc.contributor.author Bañón González, Aitor
- dc.contributor.author Wolfgeher, Don
- dc.contributor.author Jessen, Henning J.
- dc.contributor.author Alsina i Español, Berta
- dc.contributor.author Clotet Erra, Josep
- dc.contributor.author Kron, Stephen J.
- dc.contributor.author Saiardi, Adolfo
- dc.contributor.author Jiménez, Javier
- dc.contributor.author Bru, Samuel
- dc.date.accessioned 2021-12-14T06:54:53Z
- dc.date.available 2021-12-14T06:54:53Z
- dc.date.issued 2021
- dc.description.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.
- dc.description.sponsorship This work was supported by and is part of the I+D+i grant ref. PGC2018-096597-B-I00 (to J.J.) by the Spanish Ministerio de Ciencia e Innovación (MCIN). B.S.-M. was the recipient of a grant from the Agència de Gestió d’Ajuts Universitaris i de Recerca AGAUR ref. 2016FI_B 00025. H.J.J. was supported by the Deutsche Forschungsgemeinschaft (DFG) under Germany’s Excellence Strategy (CIBBS, EXC-2189, Project ID 390939984).
- dc.format.mimetype application/pdf
- dc.identifier.citation Samper-Martín B, Sarrias A, Lázaro B, Pérez-Montero M, Rodríguez-Rodríguez R, Ribeiro MPC, Bañón A, Wolfgeher D, Jessen HJ, Alsina B, Clotet J, Kron SJ, Saiardi A, Jiménez J, Bru S. Polyphosphate degradation by Nudt3-Zn 2+ mediates oxidative stress response. Cell Rep. 2021;37(7):110004. DOI: 10.1016/j.celrep.2021.110004
- dc.identifier.doi http://dx.doi.org/10.1016/j.celrep.2021.110004
- dc.identifier.issn 2211-1247
- dc.identifier.uri http://hdl.handle.net/10230/49190
- dc.language.iso eng
- dc.publisher Elsevier
- dc.relation.ispartof Cell Rep. 2021;37(7):110004
- dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/PGC2018-096597-B-I00
- dc.rights © 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/).
- dc.rights.accessRights info:eu-repo/semantics/openAccess
- dc.rights.uri https://creativecommons.org/licenses/by-nc-nd/4.0/
- dc.subject.keyword DNA damage
- dc.subject.keyword NUDIX
- dc.subject.keyword Nudt3
- dc.subject.keyword Mammalian polyphosphatase
- dc.subject.keyword Oxidative stress
- dc.subject.keyword Polyphosphate
- dc.title Polyphosphate degradation by Nudt3-Zn 2+ mediates oxidative stress response
- dc.type info:eu-repo/semantics/article
- dc.type.version info:eu-repo/semantics/publishedVersion