Evidence map›Paper›PMID 36608670›Full record

ArticleMolecular cell2023

A central role for regulated protein stability in the control of TFE3 and MITF by nutrients.

Christopher Nardone, Brad A Palanski, Daniel C Scott, Richard T Timms, Karl W Barber, Xin Gu, Aoyue Mao, Yumei Leng, Emma V Watson, Brenda A Schulman and 2 more

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

Article in Molecular cell, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed
7.1field-weighted citation impact, top 2% 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

36 citing papers in PubMed, 47 citations in OpenAlex.

  1. Review
  2. Proteasomal surveillance of exposed cysteines.bioRxiv : the preprint server for biology · 2026
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  14. Degrons: defining the rules of protein degradation.Nature reviews. Molecular cell biology · 2025
    Review
  15. Article
  16. Article
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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

12 authors at 4 institutions in 3 countries.

Christopher NardoneDivision of Genetics, Department of Medicine, Howard Hughes Medical Institute, Brigham and Women's Hospital, Boston, MA 02115, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
Brad A PalanskiDivision of Genetics, Department of Medicine, Brigham and Women's Hospital; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
Daniel C ScottDepartment of Structural Biology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Richard T TimmsCambridge Institute of Therapeutic Immunology and Infectious Disease, Department of Medicine, University of Cambridge, Jeffrey Cheah Biomedical Centre, Puddicombe Way, Cambridge, Cambridgeshire CB2 0AW, UK.
Karl W BarberDivision of Genetics, Department of Medicine, Howard Hughes Medical Institute, Brigham and Women's Hospital, Boston, MA 02115, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
Xin GuDepartment of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.
Aoyue MaoDivision of Genetics, Department of Medicine, Howard Hughes Medical Institute, Brigham and Women's Hospital, Boston, MA 02115, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA; Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA, 02138, USA.
Yumei LengDivision of Genetics, Department of Medicine, Howard Hughes Medical Institute, Brigham and Women's Hospital, Boston, MA 02115, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
Emma V WatsonDivision of Genetics, Department of Medicine, Howard Hughes Medical Institute, Brigham and Women's Hospital, Boston, MA 02115, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
Brenda A SchulmanDepartment of Structural Biology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA; Department of Molecular Machines and Signaling, Max Planck Institute of Biochemistry, Martinsried, 82152, Germany.
Philip A ColeDivision of Genetics, Department of Medicine, Brigham and Women's Hospital; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
Stephen J ElledgeDivision of Genetics, Department of Medicine, Howard Hughes Medical Institute, Brigham and Women's Hospital, Boston, MA 02115, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA. Electronic address: selledge@genetics.med.harvard.edu.
Brigham and Women's Hospital · USSt. Jude Children's Research Hospital · USHarvard University · USUniversity of Cambridge · GB

Funding

Ubiquitin Mediated Proteolysis and Cell Cycle ControlR01AG011085 · NIA · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI JEFFREY W HARPER · 1993 to 2026
$10.9M
Chemical Approaches to Protein PhosphorylationR01CA074305 · NCI · JOHNS HOPKINS UNIVERSITY · PI COLE, PHILIP A · 2002 to 2025
$8.0M
Chemical Biology of the Control of Neddylation by DCN1R01CA247365 · NCI · UNIVERSITY OF KENTUCKY · PI GUY, RODNEY KIPLIN, SCHULMAN, BRENDA A · 2019 to 2023
$3.2M
Chemical Rescue of Protein Kinases for Cell Signaling ApplicationsF32CA259214 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI PALANSKI, BRAD ANDREW · 2021 to 2022
$136k
Howard Hughes Medical InstituteNCI NIH HHS F32 CA259214NCI NIH HHS R01 CA074305NCI NIH HHS R01 CA247365NIA NIH HHS R01 AG011085Wellcome TrustWellcome Trust 201387/Z/16/Z
6 · The paper itself

Abstract

The TFE3 and MITF master transcription factors maintain metabolic homeostasis by regulating lysosomal, melanocytic, and autophagy genes. Previous studies posited that their cytosolic retention by 14-3-3, mediated by the Rag GTPases-mTORC1, was key for suppressing transcriptional activity in the presence of nutrients. Here, we demonstrate using mammalian cells that regulated protein stability plays a fundamental role in their control. Amino acids promote the recruitment of TFE3 and MITF to the lysosomal surface via the Rag GTPases, activating an evolutionarily conserved phospho-degron and leading to ubiquitination by CUL1

Indexed as

Amino AcidsMicrophthalmia-Associated Transcription FactorAnimalsBasic Helix-Loop-Helix Leucine Zipper Transcription FactorsLysosomesMammalsMechanistic Target of Rapamycin Complex 1NutrientsProtein StabilityAmino AcidsBasic Helix-Loop-Helix Leucine Zipper Transcription FactorsMechanistic Target of Rapamycin Complex 1Microphthalmia-Associated Transcription FactorNutrientskidney cancerlysosomesMITFmTORC1neurodevelopmentnutrient-sensingphospho-degronRag GTPasesTFE3ubiquitinβ-TrCP

Identifiers

PMID36608670
PMCPMC9908011
OpenAlexW4313560927

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.