ArticleProceedings of the National Academy of Sciences of the United States of America2025
Genesis and regulation of C-terminal cyclic imides from protein damage.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 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
11 citing papers in PubMed.
- Safety considerations for cereblon-recruiting targeted protein degraders.Nature reviews. Drug discovery · 2026Review
- Contemporary design of small-molecule kinase modulators: orthosteric, allosteric and induced-proximity strategies.Nature reviews. Drug discovery · 2026Review
- PCMT1 generates the C-terminal cyclic imide degron on CRBN substrates.Nature chemical biology · 2026Article
- Aspartimide Modification in RiPP Natural Products.Biochemistry · 2026Review
- Cereblon induces G3BP2 neosubstrate degradation using molecular surface mimicry.Nature structural & molecular biology · 2026Article
- Chemical and Enzymatic Approaches to C-Terminal Cyclic Imide Formation.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Emerging opportunities in the rewiring of biology through proximity inducing small molecules.RSC medicinal chemistry · 2025Article
- A method for the detection and enrichment of endogenous cereblon substrates.Cell chemical biology · 2025Article
- A method for the detection and enrichment of endogenous cereblon substrates.bioRxiv : the preprint server for biology · 2025Article
- Repair of Isoaspartyl Residues by PCMT1 and Kidney Fibrosis.Journal of the American Society of Nephrology : JASN · 2025Article
- Genesis and regulation of C-terminal cyclic imides from protein damage.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
Corrections and comments
- Update of
Authors and funding
8 authors.
Funding
Abstract
C-Terminal cyclic imides are posttranslational modifications that can arise from spontaneous intramolecular cleavage of asparagine or glutamine residues resulting in a form of irreversible protein damage. These protein damage events are recognized and removed by the E3 ligase substrate adapter cereblon (CRBN), indicating that these aging-related modifications may require cellular quality control mechanisms to prevent deleterious effects. However, the factors that determine protein or peptide susceptibility to C-terminal cyclic imide formation or their effect on protein stability have not been explored in detail. Here, we characterize the primary and secondary structures of peptides and proteins that promote intrinsic formation of C-terminal cyclic imides in comparison to deamidation, a related form of protein damage. Extrinsic effects from solution properties and stressors on the cellular proteome additionally promote C-terminal cyclic imide formation on proteins like glutathione synthetase that are susceptible to aggregation if the protein damage products are not removed by CRBN. This systematic investigation provides insight into the regions of the proteome that are prone to these unexpectedly frequent modifications, the effects of this form of protein damage on protein stability, and the biological role of CRBN.
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.