000062015 001__ 62015
000062015 005__ 20190709135434.0
000062015 0247_ $$2doi$$a10.1371/journal.pone.0179988
000062015 0248_ $$2sideral$$a101054
000062015 037__ $$aART-2017-101054
000062015 041__ $$aeng
000062015 100__ $$0(orcid)0000-0002-6794-3535$$aLatorre, P.$$uUniversidad de Zaragoza
000062015 245__ $$aO-GlcNAcylation mediates the control of cytosolic phosphoenolpyruvate carboxykinase activity via Pgc1a
000062015 260__ $$c2017
000062015 5060_ $$aAccess copy available to the general public$$fUnrestricted
000062015 5203_ $$aPGC1a 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.
000062015 536__ $$9info:eu-repo/grantAgreement/ES/UZ/2015-BIO-01$$9info:eu-repo/grantAgreement/ES/UZ/2014-CIE-03$$9info:eu-repo/grantAgreement/ES/MEC/AGL2015–66177-R
000062015 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000062015 590__ $$a2.766$$b2017
000062015 591__ $$aMULTIDISCIPLINARY SCIENCES$$b15 / 64 = 0.234$$c2017$$dQ1$$eT1
000062015 592__ $$a1.164$$b2017
000062015 593__ $$aAgricultural and Biological Sciences (miscellaneous)$$c2017$$dQ1
000062015 593__ $$aMedicine (miscellaneous)$$c2017$$dQ1
000062015 593__ $$aBiochemistry, Genetics and Molecular Biology (miscellaneous)$$c2017$$dQ1
000062015 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000062015 700__ $$0(orcid)0000-0001-6256-5478$$aVarona, L.$$uUniversidad de Zaragoza
000062015 700__ $$0(orcid)0000-0001-9147-089X$$aBurgos, C.$$uUniversidad de Zaragoza
000062015 700__ $$0(orcid)0000-0003-0062-1029$$aCarrodeguas, J.A.$$uUniversidad de Zaragoza
000062015 700__ $$0(orcid)0000-0001-5992-2913$$aLópez-Buesa, P.$$uUniversidad de Zaragoza
000062015 7102_ $$11001$$2420$$aUniversidad de Zaragoza$$bDpto. Anatom.,Embri.Genét.Ani.$$cÁrea Genética
000062015 7102_ $$11002$$2060$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Bioquímica y Biolog.Mole.
000062015 7102_ $$12008$$2780$$aUniversidad de Zaragoza$$bDpto. Produc.Animal Cienc.Ali.$$cÁrea Tecnología de Alimentos
000062015 773__ $$g12, 6 (2017), 0179988 [14 pp]$$pPLoS One$$tPloS one$$x1932-6203
000062015 8564_ $$s3615772$$uhttps://zaguan.unizar.es/record/62015/files/texto_completo.pdf$$yVersión publicada
000062015 8564_ $$s107247$$uhttps://zaguan.unizar.es/record/62015/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000062015 909CO $$ooai:zaguan.unizar.es:62015$$particulos$$pdriver
000062015 951__ $$a2019-07-09-11:33:15
000062015 980__ $$aARTICLE