62015 20190709135434.0 doi 10.1371/journal.pone.0179988 sideral 101054 ART-2017-101054 eng (orcid)0000-0002-6794-3535 Latorre, P. Universidad de Zaragoza O-GlcNAcylation mediates the control of cytosolic phosphoenolpyruvate carboxykinase activity via Pgc1a 2017 Access copy available to the general public Unrestricted PGC1a is a coactivator of many transcription factors and cytosolic phosphoenolpyruvate carboxykinase (PCK1) is a key enzyme for gluconeogenesis. PGC1a interacts with the transcription factor PPAR¿ to stimulate PCK1 expression and thus de novo glucose synthesis. These proteins are not only important for central energy metabolism but also for supplying intermediates for other metabolic pathways, including lipidogenesis and protein synthesis and might therefore be important factors in the ethiopathogenesis of metabolic disorders like diabetes but also in other pathologies like cancer. Since polymorphisms in these proteins have been related to some phenotypic traits in animals like pigs and PGC1a G482S polymorphism increases fat deposition in humans, we have investigated the molecular basis of such effects focusing on a commonly studied polymorphism in pig Pgc1a, which changes a cysteine at position 430 (WT) of the protein to a serine (C430S). Biochemical analyses show that Pgc1a WT stimulates higher expression of human PCK1 in HEK293T and HepG2 cells. Paradoxically, Pgc1a WT is less stable than Pgc1a p.C430S in HEK293T cells. However, the study of different post-translational modifications shows a higher O-GlcNAcylation level of Pgc1a p.C430S. This higher O-GlcNAcylation level significantly decreases the interaction between Pgc1a and PPAR¿ demonstrating the importance of post-translational glycosylation of PGC1a in the regulation of PCK1 activity. This, furthermore, could explain at least in part the observed epistatic effects between PGC1a and PCK1 in pigs. info:eu-repo/grantAgreement/ES/UZ/2015-BIO-01 info:eu-repo/grantAgreement/ES/UZ/2014-CIE-03 info:eu-repo/grantAgreement/ES/MEC/AGL2015–66177-R info:eu-repo/semantics/openAccess by http://creativecommons.org/licenses/by/3.0/es/ 2.766 2017 MULTIDISCIPLINARY SCIENCES 15 / 64 = 0.234 2017 Q1 T1 1.164 2017 Agricultural and Biological Sciences (miscellaneous) 2017 Q1 Medicine (miscellaneous) 2017 Q1 Biochemistry, Genetics and Molecular Biology (miscellaneous) 2017 Q1 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion (orcid)0000-0001-6256-5478 Varona, L. Universidad de Zaragoza (orcid)0000-0001-9147-089X Burgos, C. Universidad de Zaragoza (orcid)0000-0003-0062-1029 Carrodeguas, J.A. Universidad de Zaragoza (orcid)0000-0001-5992-2913 López-Buesa, P. Universidad de Zaragoza 1001 420 Universidad de Zaragoza Dpto. Anatom.,Embri.Genét.Ani. Área Genética 1002 060 Universidad de Zaragoza Dpto. Bioq.Biolog.Mol. Celular Área Bioquímica y Biolog.Mole. 2008 780 Universidad de Zaragoza Dpto. Produc.Animal Cienc.Ali. Área Tecnología de Alimentos 12, 6 (2017), 0179988 [14 pp] PLoS One PloS one 1932-6203 3615772 http://zaguan.unizar.es/record/62015/files/texto_completo.pdf Versión publicada 107247 http://zaguan.unizar.es/record/62015/files/texto_completo.jpg?subformat=icon icon Versión publicada oai:zaguan.unizar.es:62015 articulos driver 2019-07-09-11:33:15 ARTICLE