ArticleNature chemical biology2018
Molecular basis of GID4-mediated recognition of degrons for the Pro/N-end rule pathway.
Article in Nature chemical biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 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
66 citing papers in PubMed, 112 citations in OpenAlex.
- The molecular glue CLEO4-88 inhibits the ACAA1 thiolase by induced binding to GID4.Nature chemical biology · 2026Article
- Molecular insights into NLRP1 Gly/N-degron recognition by CRL2Acta crystallographica. Section F, Structural biology communications · 2026Article
- Proteome-wide C-degron activity profiling connects conditional regulation of the CTLH E3 ligase complex to ribosome biogenesis.bioRxiv : the preprint server for biology · 2026Article
- The CTLH ubiquitin ligase substrates ZMYND19 and MKLN1 negatively regulate mTORC1 at the lysosomal membrane.Nature communications · 2025Article
- The many faces of the GID/CTLH E3 ligase complex.Biochemical Society transactions · 2025Review
- MKLN1-dependent GID4/CTLH E3 ubiquitin ligase complex assemblies are required to support B-cell antibody diversification.Journal of immunology (Baltimore, Md. : 1950) · 2025Article
- The generation and consequences of N-terminal proteoform diversity.Cell reports · 2025Review
- Design of PROTACs utilizing the E3 ligase GID4 for targeted protein degradation.Nature structural & molecular biology · 2025Article
- Insights into the degradation mechanism of GID4-based proteolysis-targeting chimeras.Nature structural & molecular biology · 2025Article
- GID4 recognition of Pro/N-degron peptides: Conformational selection and induced fit.Biophysical journal · 2025Article
- Interplay between β-propeller subunits WDR26 and muskelin regulates the CTLH E3 ligase supramolecular complex.Communications biology · 2024Article
- The hGIDLife science alliance · 2024Article
- Structural basis for C-degron selectivity across KLHDCX family E3 ubiquitin ligases.Nature communications · 2024Article
- N-degron pathways.Proceedings of the National Academy of Sciences of the United States of America · 2024Review
- A chemical probe to modulate human GID4 Pro/N-degron interactions.Nature chemical biology · 2024Article
- A key to unlock ubiquitin ligase function.Nature chemical biology · 2024Article
- FAM72A degrades UNG2 through the GID/CTLH complex to promote mutagenic repair during antibody maturation.Nature communications · 2024Article
- Molecular insights into degron recognition by CRL5Nature communications · 2024Article
- mTORC1-CTLH E3 ligase regulates the degradation of HMG-CoA synthase 1 through the Pro/N-degron pathway.Molecular cell · 2024Article
- Non-canonical substrate recognition by the human WDR26-CTLH E3 ligase regulates prodrug metabolism.Molecular cell · 2024Article
6 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The N-end rule pathway senses the N-terminal destabilizing residues of degradation substrates for the ubiquitin-proteasome system, whose integrity shields against various human syndromes including cancer and cardiovascular diseases. GID4, a subunit of the ubiquitin ligase GID complex, has been recently identified as the N-recognin of the new branch of the N-end rule pathway responsible for recognizing substrates bearing N-terminal proline residues (Pro/N-degrons). However, the molecular mechanism of GID4-mediated Pro/N-degron recognition remains largely unexplored. Here, we report the first crystal structures of human GID4 alone and in complex with various Pro/N-degrons. Our complex crystal structures, together with biophysical analyses, delineate the GID4-mediated Pro/N-degron recognition mechanism and substrate selection criteria for the Pro/N-end rule pathway. These mechanistic data on the Pro/N-recognin activity of GID4 will serve as a foundation to facilitate the identification of authentic physiological substrates as well as the development of inhibitors of therapeutic values for the Pro/N-end rule pathway.
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.