Evidence map›Paper›PMID 38325378›Full record

ArticleMolecular cell2024

The GATOR2 complex maintains lysosomal-autophagic function by inhibiting the protein degradation of MiT/TFEs.

Shu Yang, Chun-Yuan Ting, Mary A Lilly

Open access · greenAbstract read
In one paragraph

Article in Molecular cell, 2024. 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
1.5field-weighted citation impact, top 18% 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. Article
  2. Review
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

3 authors at 1 institution in 1 country.

Shu YangEunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
Chun-Yuan TingEunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
Mary A LillyEunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: lillym@nih.gov.
National Institutes of Health · US

Funding

Cell Cycle Regulation In OogenesisZIAHD001613 · NICHD · EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT · PI LILLY, MARY A · 2009 to 2025
$22.3M
Resource Component: Acquisition, maintenance and distribution of Drosophila stocksP40OD018537 · OD · TRUSTEES OF INDIANA UNIVERSITY · PI KEVIN R COOK · 2014 to 2026
$13.5M
CELL CYCLE REGULATION IN OOGENESISZ01HD001613 · NICHD · EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT · PI LILLY, MARY A · 1998 to 2008
$1.6M
Origin, diversification and function of pancreatic cancer associated fibroblastsK99CA263005 · NCI · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI HAN, LU · 2023 to 2024
$156k
Intramural NIH HHS Z01 HD001613Intramural NIH HHS Z99 HD999999NCI NIH HHS K99 CA263005NIH HHS P40 OD018537
6 · The paper itself

Abstract

Lysosomes are central to metabolic homeostasis. The microphthalmia bHLH-LZ transcription factors (MiT/TFEs) family members MITF, TFEB, and TFE3 promote the transcription of lysosomal and autophagic genes and are often deregulated in cancer. Here, we show that the GATOR2 complex, an activator of the metabolic regulator TORC1, maintains lysosomal function by protecting MiT/TFEs from proteasomal degradation independent of TORC1, GATOR1, and the RAG GTPase. We determine that in GATOR2 knockout HeLa cells, members of the MiT/TFEs family are ubiquitylated by a trio of E3 ligases and are degraded, resulting in lysosome dysfunction. Additionally, we demonstrate that GATOR2 protects MiT/TFE proteins in pancreatic ductal adenocarcinoma and Xp11 translocation renal cell carcinoma, two cancers that are driven by MiT/TFE hyperactivation. In summary, we find that the GATOR2 complex has independent roles in TORC1 regulation and MiT/TFE protein protection and thus is central to coordinating cellular metabolism with control of the lysosomal-autophagic system.

Indexed as

Kidney NeoplasmsMicrophthalmia-Associated Transcription FactorAutophagyBasic Helix-Loop-Helix Leucine Zipper Transcription FactorsHeLa CellsHumansLysosomesMechanistic Target of Rapamycin Complex 1ProteinsProteolysisBasic Helix-Loop-Helix Leucine Zipper Transcription FactorsMechanistic Target of Rapamycin Complex 1Microphthalmia-Associated Transcription FactorProteinsautophagyE3 ligasesGATOR2lysosomeMiT/TFEspancreatic ductal adenocarcinomarenal cell carcinomaTORC1ubiquitination

Identifiers

PMID38325378
PMCPMC10940221
OpenAlexW4391563662

What OpenQuestion holds

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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.