000130445 001__ 130445
000130445 005__ 20240125162930.0
000130445 0247_ $$2doi$$a10.1016/j.molcel.2018.07.031
000130445 0248_ $$2sideral$$a108074
000130445 037__ $$aART-2018-108074
000130445 041__ $$aeng
000130445 100__ $$0(orcid)0000-0002-6794-3535$$aLatorre-Muro, Pedro$$uUniversidad de Zaragoza
000130445 245__ $$aDynamic Acetylation of Phosphoenolpyruvate Carboxykinase Toggles Enzyme Activity between Gluconeogenic and Anaplerotic Reactions
000130445 260__ $$c2018
000130445 5060_ $$aAccess copy available to the general public$$fUnrestricted
000130445 5203_ $$aCytosolic phosphoenolpyruvate carboxykinase (PCK1) is considered a gluconeogenic enzyme; however, its metabolic functions and regulatory mechanisms beyond gluconeogenesis are poorly understood. Here, we describe that dynamic acetylation of PCK1 interconverts the enzyme between gluconeogenic and anaplerotic activities. Under high glucose, p300-dependent hyperacetylation of PCK1 did not lead to protein degradation but instead increased the ability of PCK1 to perform the anaplerotic reaction, converting phosphoenolpyruvate to oxaloacetate. Lys91 acetylation destabilizes the active site of PCK1 and favors the reverse reaction. At low energy input, we demonstrate that SIRT1 deacetylates PCK1 and fully restores the gluconeogenic ability of PCK1. Additionally, we found that GSK3 beta-mediated phosphorylation of PCK1 decreases acetylation and increases ubiquitination. Biochemical evidence suggests that serine phosphorylation adjacent to Lys91 stimulates SIRT1-dependent deacetylation of PCK1. This work reveals an unexpected capacity of hyper-acetylated PCK1 to promote anaplerotic activity, and the intersection of post-translational control of PCK1 involving acetylation, phosphorylation, and ubiquitination.
000130445 536__ $$9info:eu-repo/grantAgreement/ES/MEC/BFU2016-75633-P$$9info:eu-repo/grantAgreement/ES/MEC/CTQ2013-44367-C2-2-P$$9info:eu-repo/grantAgreement/ES/MINECO/AGL2015-66177$$9info:eu-repo/grantAgreement/ES/UZ-IBERCAJA-CAI/CM1-16$$9info:eu-repo/grantAgreement/ES/UZ/UZ2014-CIE-03$$9info:eu-repo/grantAgreement/ES/UZ/UZ2015-BIO-01
000130445 540__ $$9info:eu-repo/semantics/openAccess$$aby-nc-nd$$uhttp://creativecommons.org/licenses/by-nc-nd/3.0/es/
000130445 590__ $$a14.548$$b2018
000130445 591__ $$aCELL BIOLOGY$$b11 / 191 = 0.058$$c2018$$dQ1$$eT1
000130445 591__ $$aBIOCHEMISTRY & MOLECULAR BIOLOGY$$b6 / 294 = 0.02$$c2018$$dQ1$$eT1
000130445 592__ $$a12.076$$b2018
000130445 593__ $$aMolecular Biology$$c2018$$dQ1
000130445 593__ $$aCell Biology$$c2018$$dQ1
000130445 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000130445 700__ $$aBaeza, J.
000130445 700__ $$aArmstrong, E.A.
000130445 700__ $$0(orcid)0000-0002-3122-9401$$aHurtado-Guerrero, Ramón$$uUniversidad de Zaragoza
000130445 700__ $$aCorzana, F.
000130445 700__ $$aWu, L.E.
000130445 700__ $$aSinclair, D.A.
000130445 700__ $$0(orcid)0000-0001-5992-2913$$aLópez-Buesa, Pascual$$uUniversidad de Zaragoza
000130445 700__ $$0(orcid)0000-0003-0062-1029$$aCarrodeguas, José A.$$uUniversidad de Zaragoza
000130445 700__ $$aDenu, J.M.
000130445 7102_ $$11002$$2060$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Bioquímica y Biolog.Mole.
000130445 7102_ $$12008$$2780$$aUniversidad de Zaragoza$$bDpto. Produc.Animal Cienc.Ali.$$cÁrea Tecnología de Alimentos
000130445 773__ $$g71, 5 (2018), 718-732.e1–e8$$pMol. cell$$tMolecular Cell$$x1097-2765
000130445 8564_ $$s5375242$$uhttps://zaguan.unizar.es/record/130445/files/texto_completo.pdf$$yVersión publicada
000130445 8564_ $$s1660441$$uhttps://zaguan.unizar.es/record/130445/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000130445 909CO $$ooai:zaguan.unizar.es:130445$$particulos$$pdriver
000130445 951__ $$a2024-01-25-15:11:09
000130445 980__ $$aARTICLE