ArticleThe Biochemical journal2020
The structure of importin α and the nuclear localization peptide of ChREBP, and small compound inhibitors of ChREBP-importin α interactions.
Article in The Biochemical journal, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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.
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.
Who cites it
10 citing papers in PubMed, 16 citations in OpenAlex.
- Sugar Shockwaves: How the Fructose-Glucose-ChREBP Pathway Hijacks Liver Metabolism.Life (Basel, Switzerland) · 2026Review
- Extreme multivalency and a composite short linear motif facilitate PCNA-binding, localisation and abundance of p21 (CDKN1A).The FEBS journal · 2025Article
- Molecular glues of the regulatory ChREBP/14-3-3 complex protect beta cells from glucolipotoxicity.Nature communications · 2025Article
- Molecular glues of the regulatory ChREBP/14-3-3 complex protect beta cells from glucolipotoxicity.bioRxiv : the preprint server for biology · 2024Article
- Pathogenic mutations of human phosphorylation sites affect protein-protein interactions.Nature communications · 2024Article
- The transcription factor ChREBP Orchestrates liver carcinogenesis by coordinating the PI3K/AKT signaling and cancer metabolism.Nature communications · 2024Article
- CDK6 inhibits de novo lipogenesis in white adipose tissues but not in the liver.Nature communications · 2024Article
- The Function of MondoA and ChREBP Nutrient-Sensing Factors in Metabolic Disease.International journal of molecular sciences · 2023Review
- ChREBP deficiency prevents high sucrose diet-induced obesity through reducing sucrase expression.Journal of clinical biochemistry and nutrition · 2022Article
- Nuclear-Import Receptors Counter Deleterious Phase Transitions in Neurodegenerative Disease.Journal of molecular biology · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The carbohydrate response element binding protein (ChREBP) is a glucose-responsive transcription factor that plays a critical role in glucose-mediated induction of genes involved in hepatic glycolysis and lipogenesis. In response to fluctuating blood glucose levels ChREBP activity is regulated mainly by nucleocytoplasmic shuttling of ChREBP. Under high glucose ChREBP binds to importin α and importin β and translocates into the nucleus to initiate transcription. We have previously shown that the nuclear localization signal site (NLS) for ChREBP is bipartite with the NLS extending from Arg158 to Lys190. Here, we report the 2.5 Å crystal structure of the ChREBP-NLS peptide bound to importin α. The structure revealed that the NLS binding is monopartite, with the amino acid residues K171RRI174 from the ChREBP-NLS interacting with ARM2-ARM5 on importin α. We discovered that importin α also binds to the primary binding site of the 14-3-3 proteins with high affinity, which suggests that both importin α and 14-3-3 are each competing with the other for this broad-binding region (residues 117-196) on ChREBP. We screened a small compound library and identified two novel compounds that inhibit the ChREBP-NLS/importin α interaction, nuclear localization, and transcription activities of ChREBP. These candidate molecules support developing inhibitors of ChREBP that may be useful in treatment of obesity and the associated diseases.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.