Evidence map›Paper›PMID 30193097›Full record

ArticleMolecular cell2018

Dynamic Acetylation of Phosphoenolpyruvate Carboxykinase Toggles Enzyme Activity between Gluconeogenic and Anaplerotic Reactions.

Pedro Latorre-Muro, Josue Baeza, Eric A Armstrong, Ramón Hurtado-Guerrero, Francisco Corzana, Lindsay E Wu, David A Sinclair, Pascual López-Buesa, José A Carrodeguas, John M Denu

Open access · bronzeAbstract read
In one paragraph

Article in Molecular cell, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.

0numbers the graph read from it
0cells of the map it votes in
41citing papers in PubMed
3.8field-weighted citation impact, top 7% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

41 citing papers in PubMed, 67 citations in OpenAlex.

  1. Science advances · 2023
    Trial
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  3. A NovelJIMD reports · 2026
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 6 institutions in 3 countries.

Pedro Latorre-MuroDepartamento de Producción Animal y Ciencia de los Alimentos, Facultad de Veterinaria, Universidad de Zaragoza, 50013 Zaragoza, Spain; Instituto de Biocomputación y Física de Sistemas Complejos (BIFI), BIFIIQFR (CSIC) Joint Unit, Universidad de Zaragoza, 50018 Zaragoza, Spain.
Josue BaezaWisconsin Institute for Discovery and Department of Biomolecular Chemistry, University of Wisconsin School of Medicine and Public Health-Madison, Madison, WI 53715, USA.
Eric A ArmstrongWisconsin Institute for Discovery and Department of Biomolecular Chemistry, University of Wisconsin School of Medicine and Public Health-Madison, Madison, WI 53715, USA.
Ramón Hurtado-GuerreroInstituto de Biocomputación y Física de Sistemas Complejos (BIFI), BIFIIQFR (CSIC) Joint Unit, Universidad de Zaragoza, 50018 Zaragoza, Spain; Fundación ARAID, Government of Aragón, Zaragoza, Spain.
Francisco CorzanaDepartamento de Química, Centro de Investigación en Síntesis Química, Universidad de La Rioja, 26006 Logroño, Spain.
Lindsay E WuDepartment of Pharmacology, School of Medical Sciences, The University of New South Wales, Sydney, NSW 2052, Australia.
David A SinclairDepartment of Pharmacology, School of Medical Sciences, The University of New South Wales, Sydney, NSW 2052, Australia; Department of Genetics, Paul F. Glenn Laboratories for the Biological Mechanisms of Aging, Harvard Medical School, Boston, MA 02115, USA.
Pascual López-BuesaDepartamento de Producción Animal y Ciencia de los Alimentos, Facultad de Veterinaria, Universidad de Zaragoza, 50013 Zaragoza, Spain; Instituto de Biocomputación y Física de Sistemas Complejos (BIFI), BIFIIQFR (CSIC) Joint Unit, Universidad de Zaragoza, 50018 Zaragoza, Spain.
José A CarrodeguasInstituto de Biocomputación y Física de Sistemas Complejos (BIFI), BIFIIQFR (CSIC) Joint Unit, Universidad de Zaragoza, 50018 Zaragoza, Spain; Departamento de Bioquímica y Biología Molecular y Celular, Facultad de Ciencias, Universidad de Zaragoza, 50009 Zaragoza, Spain; IIS Aragón, Zaragoza, Spain. Electronic address: carrode@unizar.es.
John M DenuWisconsin Institute for Discovery and Department of Biomolecular Chemistry, University of Wisconsin School of Medicine and Public Health-Madison, Madison, WI 53715, USA; Morgridge Institute for Research, Madison, WI 53715, USA. Electronic address: john.denu@wisc.edu.
Universidad de Zaragoza · ESUNSW Sydney · AUWisconsin Institutes for Discovery · USInstituto de Investigación Sanitaria Aragón · ESMorgridge Institute for Research · USUniversidad de La Rioja · ES

Funding

Reversible protein acetylation and sirtuin functionR01GM065386 · NIGMS · UNIVERSITY OF WISCONSIN-MADISON · PI DENU, JOHN M · 2003 to 2022
$7.3M
Uncovering the Human SecretomeDP1AG058605 · NIA · HARVARD MEDICAL SCHOOL · PI SINCLAIR, DAVID A. · 2017 to 2021
$5.9M
Role of Sgs1 DNA helicase in telomere maintenanceR01AG019719 · NIA · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI SINCLAIR, DAVID A. · 2001 to 2022
$5.3M
SIRT1 as a regulator of health and lifespan of mammalsR37AG028730 · NIA · HARVARD MEDICAL SCHOOL · PI SINCLAIR, DAVID A. · 2012 to 2021
$4.1M
Elucidating mechanisms of SIRT1 activationR01DK100263 · NIDDK · HARVARD MEDICAL SCHOOL · PI SINCLAIR, DAVID A. · 2016 to 2020
$2.5M
SIRT as a regulator of health and lifespan of mammalsR01AG028730 · NIA · HARVARD MEDICAL SCHOOL · PI SINCLAIR, DAVID A. · 2007 to 2011
$1.7M
Nicotinamide Mononucleotide (NMN) as a Novel Therapeutic in the Treatment of Oral MucositisR21DE027490 · NIDCR · HARVARD MEDICAL SCHOOL · PI SINCLAIR, DAVID A. · 2018 to 2019
$466k
NIA NIH HHS DP1 AG058605NIA NIH HHS R01 AG019719NIA NIH HHS R01 AG028730NIA NIH HHS R37 AG028730NIDCR NIH HHS R21 DE027490NIDDK NIH HHS R01 DK100263NIGMS NIH HHS R01 GM065386
6 · The paper itself

Abstract

Cytosolic 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 GSK3β-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 hyperacetylated PCK1 to promote anaplerotic activity, and the intersection of post-translational control of PCK1 involving acetylation, phosphorylation, and ubiquitination.

Indexed as

AcetylationAnimalsCatalytic DomainCell LineCell Line, TumorFemaleGluconeogenesisGlycogen Synthase Kinase 3 betaHEK293 CellsHep G2 CellsHumansMaleMiceMice, Inbred C57BLMice, KnockoutPhosphoenolpyruvate Carboxykinase (GTP)Glycogen Synthase Kinase 3 betaPhosphoenolpyruvate Carboxykinase (GTP)Sirtuin 1acetylationacetyltransferaseanaplerosisgluconeogenesismetabolismphosphoenolpyruvate carboxykinasephosphorylationpost-translational modificationregulationsirtuin

Identifiers

PMID30193097
PMCPMC6188669
OpenAlexW2890685630

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.