Evidence map›Paper›PMID 37221017›Full record

ArticleLife science alliance2023

MAP4K3 inhibits Sirtuin-1 to repress the LKB1-AMPK pathway to promote amino acid-dependent activation of the mTORC1 complex.

Mary Rose Branch, Cynthia L Hsu, Kohta Ohnishi, Wen-Chuan Shen, Elian Lee, Jill Meisenhelder, Brett Winborn, Bryce L Sopher, J Paul Taylor, Tony Hunter and 1 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Life science alliance, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.9field-weighted citation impact, top 25% 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

2 citing papers in PubMed, 4 citations in OpenAlex.

  1. Review
  2. Article
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

11 authors at 5 institutions in 1 country.

Mary Rose BranchDepartments of Pathology & Laboratory Medicine, Neurology, and Biological Chemistry, University of California, Irvine, CA, USA.ORCID https://orcid.org/0000-0002-3410-1534
Cynthia L HsuDepartment of Pediatrics, University of California, San Diego; La Jolla, CA, USA.
Kohta OhnishiDepartment of Pediatrics, University of California, San Diego; La Jolla, CA, USA.
Wen-Chuan ShenDepartments of Pathology & Laboratory Medicine, Neurology, and Biological Chemistry, University of California, Irvine, CA, USA.
Elian LeeDepartment of Pediatrics, University of California, San Diego; La Jolla, CA, USA.
Jill MeisenhelderMolecular and Cellular Biology Laboratory, Salk Institute, La Jolla, CA, USA.
Brett WinbornDepartment of Cell and Molecular Biology, St. Jude Children's Research Hospital, Memphis, TN, USA.
Bryce L SopherDepartment of Pathology, University of Washington Medical Center, Seattle, WA, USA.
J Paul TaylorDepartment of Cell and Molecular Biology, St. Jude Children's Research Hospital, Memphis, TN, USA.
Tony HunterMolecular and Cellular Biology Laboratory, Salk Institute, La Jolla, CA, USA.
Albert R La SpadaDepartments of Pathology & Laboratory Medicine, Neurology, and Biological Chemistry, University of California, Irvine, CA, USA alaspada@uci.edu.ORCID https://orcid.org/0000-0001-6151-2964
University of California San Diego · USDuke University · USSalk Institute for Biological Studies · USSt. Jude Children's Research Hospital · USUniversity of Washington Medical Center · US

Funding

Viral Vector Core (VVC)P30CA014195 · NCI · SALK INSTITUTE FOR BIOLOGICAL STUDIES · PI Reuben Shaw · 1985 to 2026
$82.8M
Training Program in Basic Clinical GeneticsT32GM008666 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI HAMILTON, BRUCE A · 1998 to 2021
$8.6M
La Spada Outstanding Investigator AwardR35NS122140 · NINDS · UNIVERSITY OF CALIFORNIA-IRVINE · PI ALBERT R LA SPADA · 2021 to 2026
$7.2M
Salk Institute for Biological Studies NINDS Center Core GrantP30NS072031 · NINDS · SALK INSTITUTE FOR BIOLOGICAL STUDIES · PI GOULDING, MARTYN D · 2011 to 2015
$4.2M
Molecular genetic regulation of autophagy in health and neurodegenerative diseaseR01AG033082 · NIA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI LA SPADA, ALBERT R · 2009 to 2019
$4.0M
MAP4K3 regulation of cellular stress response pathways in health and diseaseRF1AG033082 · NIA · UNIVERSITY OF CALIFORNIA-IRVINE · PI LA SPADA, ALBERT R · 2022 to 2025
$3.3M
NCI NIH HHS P30 CA014195NIA NIH HHS R01 AG033082NIA NIH HHS RF1 AG033082NIGMS NIH HHS T32 GM008666NINDS NIH HHS P30 NS072031NINDS NIH HHS R35 NS122140
6 · The paper itself

Abstract

mTORC1 is the key rheostat controlling the cellular metabolic state. Of the various inputs to mTORC1, the most potent effector of intracellular nutrient status is amino acid supply. Despite an established role for MAP4K3 in promoting mTORC1 activation in the presence of amino acids, the signaling pathway by which MAP4K3 controls mTORC1 activation remains unknown. Here, we examined the process of MAP4K3 regulation of mTORC1 and found that MAP4K3 represses the LKB1-AMPK pathway to achieve robust mTORC1 activation. When we sought the regulatory link between MAP4K3 and LKB1 inhibition, we discovered that MAP4K3 physically interacts with the master nutrient regulatory factor sirtuin-1 (SIRT1) and phosphorylates SIRT1 to repress LKB1 activation. Our results reveal the existence of a novel signaling pathway linking amino acid satiety with MAP4K3-dependent suppression of SIRT1 to inactivate the repressive LKB1-AMPK pathway and thereby potently activate the mTORC1 complex to dictate the metabolic disposition of the cell.

Indexed as

AMP-Activated Protein KinasesSirtuin 1Amino AcidsMechanistic Target of Rapamycin Complex 1Signal TransductionAmino AcidsAMP-Activated Protein KinasesMechanistic Target of Rapamycin Complex 1Sirtuin 1

Identifiers

PMID37221017
PMCPMC10205607
OpenAlexW4377940452

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.