Evidence map›Paper›PMID 41922353›Full record

ArticleNature communications2026

TFEB degradation is regulated by an IKK/β-TrCP2 phosphorylation-ubiquitination cascade.

Yan Xiong, Jaiprakash Sharma, Meggie N Young, Wen Xiong, Ali Jazayeri, Karl F Poncha, Ma Xenia G Ilagan, Qing Wang, Bei Gao, Hui Zheng and 2 more

Abstract read
In one paragraph

Article in Nature communications, 2026. 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
–field-weighted citation impact
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.

  1. Article
  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

12 authors.

Yan XiongDepartment of Pediatrics, Washington University in St. Louis, School of Medicine, Genetics and Genomic Medicine, Saint Louis, MO, USA.ORCID 0000-0002-9268-3907
Jaiprakash SharmaDepartment of Pediatrics, Washington University in St. Louis, School of Medicine, Genetics and Genomic Medicine, Saint Louis, MO, USA.
Meggie N YoungVerna & Marrs McLean Department of Biochemistry & Molecular Pharmacology, Baylor College of Medicine, Houston, TX, USA.ORCID 0000-0003-2684-7317
Wen XiongHuffington Center on Aging, Baylor College of Medicine, Houston, TX, USA.ORCID 0000-0002-2825-2061
Ali JazayeriDepartment of Pediatrics, Washington University in St. Louis, School of Medicine, Genetics and Genomic Medicine, Saint Louis, MO, USA.
Karl F PonchaVerna & Marrs McLean Department of Biochemistry & Molecular Pharmacology, Baylor College of Medicine, Houston, TX, USA.
Ma Xenia G IlaganHigh Throughput Screening Center, Center for drug discovery, Washington University School of Medicine, St. Louis, MO, USA.ORCID 0000-0003-2888-4859
Qing WangComplete Omics Inc., Baltimore, MD, USA.ORCID 0000-0002-7979-766X
Bei GaoDepartment of Pediatrics, Washington University in St. Louis, School of Medicine, Genetics and Genomic Medicine, Saint Louis, MO, USA.
Hui ZhengHuffington Center on Aging, Baylor College of Medicine, Houston, TX, USA.ORCID 0000-0002-5427-3798
Nicolas L YoungVerna & Marrs McLean Department of Biochemistry & Molecular Pharmacology, Baylor College of Medicine, Houston, TX, USA.ORCID 0000-0002-3323-2815
Marco SardielloDepartment of Pediatrics, Washington University in St. Louis, School of Medicine, Genetics and Genomic Medicine, Saint Louis, MO, USA. sardiello@wustl.edu.ORCID 0000-0001-6484-0250

Funding

TMEM106b as a lysosomal adaptor to influence brain aging and tau pathogenesisP01AG066606 · NIA · BAYLOR COLLEGE OF MEDICINE · PI ZHENG, HUI · 2021 to 2025
$13.5M
Systems-Level Approach to Neuronopathic Lysosomal Storage DisordersRM1NS132962 · NINDS · WASHINGTON UNIVERSITY · PI JONATHAN D COOPER, PATRICIA I DICKSON · 2023 to 2026
$6.3M
NIA NIH HHS P01 AG066606NINDS NIH HHS RM1 NS132962
6 · The paper itself

Abstract

Transcription factor EB (TFEB) is a master regulator of lysosomal biogenesis and cellular clearance pathways. TFEB activity is tightly controlled by multiple post-translational mechanisms, but the exact molecular mechanism controlling its stability has remained elusive. Here, we identify the IκB kinase (IKK) complex as a key regulator of TFEB protein stability through a phosphorylation-ubiquitination cascade. A high-content kinase inhibitor screen reveals that IKK inhibition increases TFEB protein levels, and genetic ablation of IKK components increases TFEB stability, upregulates lysosomal genes, and enhances lysosomal biogenesis and degradative capacity. Mechanistically, we show that IKK phosphorylates TFEB on a cluster of serine residues (

Indexed as

Basic Helix-Loop-Helix Leucine Zipper Transcription Factorsbeta-Transducin Repeat-Containing ProteinsI-kappa B KinaseAnimalsHEK293 CellsHumansLysosomesMicePhosphorylationProtein StabilityProteolysisUbiquitinationBasic Helix-Loop-Helix Leucine Zipper Transcription Factorsbeta-Transducin Repeat-Containing ProteinsI-kappa B KinaseTFEB protein, human

Identifiers

PMID41922353
PMCPMC13201563

What OpenQuestion holds

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LicenceCC BY-NC-ND
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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.