Evidence map›Paper›PMID 25544559›Full record

ArticleMolecular cell2015

Phosphorylation of LC3 by the Hippo kinases STK3/STK4 is essential for autophagy.

Deepti S Wilkinson, Jinel S Jariwala, Ericka Anderson, Koyel Mitra, Jill Meisenhelder, Jessica T Chang, Trey Ideker, Tony Hunter, Victor Nizet, Andrew Dillin and 1 more

Open access · bronzeAbstract read
In one paragraph

Article in Molecular cell, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 110 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
110citing papers in PubMed, 2 pooled it
9.4field-weighted citation impact, top 1% 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

110 citing papers in PubMed, 2 syntheses or guidelines pooled it, 182 citations in OpenAlex.

  1. Guideline
  2. Guideline
  3. Review
  4. Article
  5. Autophagy · 2026
    Review
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Review
  12. Neddylation modification stabilizes LC3B by antagonizing its ubiquitin-mediated degradation and promoting autophagy in skin.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  13. Article
  14. STRIPAK, a fundamental signaling hub of eukaryotic development.Microbiology and molecular biology reviews : MMBR · 2024
    Review
  15. Article
  16. Review
  17. Article
  18. Article
  19. Interplay between group AMicrobiology and molecular biology reviews : MMBR · 2024
    Review
  20. Article

50 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors at 4 institutions in 1 country.

Deepti S WilkinsonSanford-Burnham Medical Research Institute, Development, Aging, and Regeneration Program, La Jolla, CA 92037, USA.
Jinel S JariwalaSanford-Burnham Medical Research Institute, Development, Aging, and Regeneration Program, La Jolla, CA 92037, USA.
Ericka AndersonDepartment of Pediatrics, School of Medicine and Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA 92093, USA.
Koyel MitraDepartment of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
Jill MeisenhelderSalk Institute for Biological Studies, La Jolla, CA 92037, USA.
Jessica T ChangSanford-Burnham Medical Research Institute, Development, Aging, and Regeneration Program, La Jolla, CA 92037, USA.
Trey IdekerDepartment of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
Tony HunterSalk Institute for Biological Studies, La Jolla, CA 92037, USA.
Victor NizetDepartment of Pediatrics, School of Medicine and Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA 92093, USA.
Andrew DillinThe Howard Hughes Medical Institute, University of California, Berkeley, CA 94720, USA.
Malene HansenSanford-Burnham Medical Research Institute, Development, Aging, and Regeneration Program, La Jolla, CA 92037, USA. Electronic address: mhansen@sanfordburnham.org.
Sanford Burnham Prebys Medical Discovery Institute · USUniversity of California San Diego · USSalk Institute for Biological Studies · USHoward Hughes Medical Institute · US

Funding

Tumor Microenvironment and Cancer ImmunologyP30CA030199 · NCI · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI Michael Jackson · 1985 to 2026
$107.2M
Viral Vector Core (VVC)P30CA014195 · NCI · SALK INSTITUTE FOR BIOLOGICAL STUDIES · PI Ye Zheng · 1985 to 2026
$82.8M
SYNTHETIC SYSTEMSP50GM085764 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI HASTY, JEFF M, IDEKER, TREY · 2010 to 2018
$23.3M
TR&D 3 - Network Guided Machine LearningP41GM103504 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI PICO, ALEXANDER R · 2012 to 2024
$17.3M
SOMATIC CELL CYCLE REGULATION BY PHOSPHORYLATIONR01CA080100 · NCI · SALK INSTITUTE FOR BIOLOGICAL STUDIES · PI HUNTER, TONY R. · 1999 to 2018
$13.1M
SIGNAL TRANSDUCTION BY TYROSINE PHOSPHORYLATIONR01CA082683 · NCI · SALK INSTITUTE FOR BIOLOGICAL STUDIES · PI HUNTER, TONY R. · 1999 to 2019
$12.2M
Regulation of the Autophagy Process in Organismal AgingR01AG038664 · NIA · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI Malene Hansen · 2011 to 2026
$6.4M
Neuroendocrine Coordination of Mitochondrial Stress Signaling and ProteostasisR01ES021667 · NIEHS · UNIVERSITY OF CALIFORNIA BERKELEY · PI DILLIN, ANDREW G · 2012 to 2023
$4.6M
Salk Institute for Biological Studies NINDS Center Core GrantP30NS072031 · NINDS · SALK INSTITUTE FOR BIOLOGICAL STUDIES · PI O'LEARY, DENNIS D · 2011 to 2015
$4.2M
GAS Switch from Colonizing Bacterium to Invasive PathogenR01AI077780 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI NIZET, VICTOR · 2008 to 2019
$3.8M
Mechanisms of the M protein in group A Streptococcus virulenceR01AI096837 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GHOSH, PARTHO, NIZET, VICTOR · 2011 to 2015
$2.7M
Role of autophagy and lipid metabolism in organismal agingR01AG039756 · NIA · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI HANSEN, MALENE · 2011 to 2015
$1.9M
Howard Hughes Medical InstituteNCI NIH HHS CA014195-40NCI NIH HHS CA80100NCI NIH HHS CA82683NCI NIH HHS P30 CA014195NCI NIH HHS P30 CA030199NCI NIH HHS R01 CA080100NCI NIH HHS R01 CA082683NIAID NIH HHS AI077780NIAID NIH HHS AI096837NIAID NIH HHS R01 AI077780NIAID NIH HHS R01 AI096837NIAID NIH HHS R56 AI096837NIA NIH HHS AG038664NIA NIH HHS AG039756NIA NIH HHS R01 AG038664NIA NIH HHS R01 AG039756NIEHS NIH HHS R01 ES021667NIGMS NIH HHS P41 GM103504NIGMS NIH HHS P50 GM085764NINDS NIH HHS NS072031-03A1NINDS NIH HHS P30 NS072031
6 · The paper itself

Abstract

The protein LC3 is indispensible for the cellular recycling process of autophagy and plays critical roles during cargo recruitment, autophagosome biogenesis, and completion. Here, we report that LC3 is phosphorylated at threonine 50 (Thr(50)) by the mammalian Sterile-20 kinases STK3 and STK4. Loss of phosphorylation at this site blocks autophagy by impairing fusion of autophagosomes with lysosomes, and compromises the ability of cells to clear intracellular bacteria, an established cargo for autophagy. Strikingly, mutation of LC3 mimicking constitutive phosphorylation at Thr(50) reverses the autophagy block in STK3/STK4-deficient cells and restores their capacity to clear bacteria. Loss of STK3/STK4 impairs autophagy in diverse species, indicating that these kinases are conserved autophagy regulators. We conclude that phosphorylation of LC3 by STK3/STK4 is an essential step in the autophagy process. Since several pathological conditions, including bacterial infections, display aberrant autophagy, we propose that pharmacological agents targeting this regulatory circuit hold therapeutic potential.

Indexed as

AnimalsAutophagyCaenorhabditis elegansCells, CulturedEmbryo, MammalianFibroblastsGene Expression RegulationHippo KinasesHumansLysosomesMembrane FusionMiceMice, KnockoutMicrotubule-Associated ProteinsMutationPeptide FragmentsHippo KinasesMap1lc3b protein, mouseMicrotubule-Associated ProteinsPeptide FragmentsProtein Serine-Threonine KinasesSerine-Threonine Kinase 3Stk3 protein, mouseStk4 protein, mouseThreonine

Identifiers

PMID25544559
PMCPMC4373083
OpenAlexW2161199002

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.