dc.creator | González Rellán, María J. | es |
dc.creator | Fernández, Uxía | es |
dc.creator | Parracho, Tamara | es |
dc.creator | Novoa, Eva | es |
dc.creator | Fondevila, Marcos F. | es |
dc.creator | Da Silva Lima, Natalia | es |
dc.creator | Rodríguez, Amaia | es |
dc.creator | Pérez Mejías, Gonzalo | es |
dc.creator | Díaz Quintana, Antonio Jesús | es |
dc.creator | Díaz Moreno, Irene | es |
dc.creator | Nogueiras, Rubén | es |
dc.date.accessioned | 2023-09-15T13:09:57Z | |
dc.date.available | 2023-09-15T13:09:57Z | |
dc.date.issued | 2023 | |
dc.identifier.citation | González Rellán, M.J., Fernández, U., Parracho, T., Novoa, E., Fondevila, M.F., Da Silva Lima, N.,...,Nogueiras, R. (2023). Neddylation of phosphoenolpyruvate carboxykinase 1 controls glucose metabolism. Cell Metabolism, 35 (9), 1630-1645.e5. https://doi.org/10.1016/j.cmet.2023.07.003. | |
dc.identifier.issn | 1550-4131 | es |
dc.identifier.uri | https://hdl.handle.net/11441/148947 | |
dc.description.abstract | Neddylation is a post-translational mechanism that adds a ubiquitin-like protein, namely neural precursor cell expressed developmentally downregulated protein 8 (NEDD8). Here, we show that neddylation in mouse liver is modulated by nutrient availability. Inhibition of neddylation in mouse liver reduces gluconeogenic capacity and the hyperglycemic actions of counter-regulatory hormones. Furthermore, people with type 2 diabetes display elevated hepatic neddylation levels. Mechanistically, fasting or caloric restriction of mice leads to neddylation of phosphoenolpyruvate carboxykinase 1 (PCK1) at three lysine residues—K278, K342, and K387. We find that mutating the three PCK1 lysines that are neddylated reduces their gluconeogenic activity rate. Molecular dynamics simulations show that neddylation of PCK1 could re-position two loops surrounding the catalytic center into an open configuration, rendering the catalytic center more accessible. Our study reveals that neddylation of PCK1 provides a finely tuned mechanism of controlling glucose metabolism by linking whole nutrient availability to metabolic homeostasis. | es |
dc.description.sponsorship | Ministerio de Ciencia, Innovación y Universidades PID2020-117116RB-I00, BFU2017-87721, RTI2018-101840-BI00, PID2021-126096NB-I00, RED2018-102379-T | es |
dc.description.sponsorship | Xunta de Galicia 2021-CP085, 2020-PG0157 | es |
dc.description.sponsorship | Fundación BBVA RTC2019-007125-1 | es |
dc.description.sponsorship | Proyectos Investigación en Salud DTS20/00138, DTS20/00138 | es |
dc.description.sponsorship | European Community 2019-WATCH- 810331 | es |
dc.format | application/pdf | es |
dc.format.extent | 22 p. | es |
dc.language.iso | eng | es |
dc.publisher | Elsevier | es |
dc.relation.ispartof | Cell Metabolism, 35 (9), 1630-1645.e5. | |
dc.rights | Attribution-NonCommercial-NoDerivatives 4.0 Internacional | * |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | * |
dc.subject | Calorie restriction | es |
dc.subject | Fasting | es |
dc.subject | Glucagon | es |
dc.subject | Glucose metabolism | es |
dc.subject | Neddylation | es |
dc.subject | PCK1 | es |
dc.subject | Type 2 diabetes | es |
dc.title | Neddylation of phosphoenolpyruvate carboxykinase 1 controls glucose metabolism | es |
dc.type | info:eu-repo/semantics/article | es |
dc.type.version | info:eu-repo/semantics/publishedVersion | es |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | es |
dc.contributor.affiliation | Universidad de Sevilla. Departamento de Bioquímica Vegetal y Biología Molecular | es |
dc.relation.projectID | PID2020-117116RB-I00 | es |
dc.relation.projectID | BFU2017-87721 | es |
dc.relation.projectID | RTI2018-101840-BI00 | es |
dc.relation.projectID | PID2021-126096NB-I00 | es |
dc.relation.projectID | RED2018-102379-T | es |
dc.relation.projectID | 2021-CP085 | es |
dc.relation.projectID | 2020-PG0157 | es |
dc.relation.projectID | RTC2019-007125-1 | es |
dc.relation.projectID | DTS20/00138 | es |
dc.relation.projectID | DTS20/00138 | es |
dc.relation.projectID | 2019-WATCH- 810331 | es |
dc.relation.publisherversion | https://doi.org/10.1016/j.cmet.2023.07.003 | es |
dc.identifier.doi | 10.1016/j.cmet.2023.07.003 | es |
dc.journaltitle | Cell Metabolism | es |
dc.publication.volumen | 35 | es |
dc.publication.issue | 9 | es |
dc.publication.initialPage | 1630 | es |
dc.publication.endPage | 1645.e5 | es |
dc.contributor.funder | Ministerio de Ciencia, Innovación y Universidades (MICINN). España | es |
dc.contributor.funder | Xunta de Galicia | es |
dc.contributor.funder | European Community (EC) | es |