ReviewProceedings of the National Academy of Sciences of the United States of America2019
N-degron and C-degron pathways of protein degradation.
Review in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 304 papers.
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Who cites it
304 citing papers in PubMed.
- Degrading GPX4 via Biomimetic Nanoparticle-Mediated In Situ Synthesis of Deep-Learning-Designed Binder-Degron Chimeras for Prostate Cancer Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Rubisco functional integrity requires a dedicated three-step maturation pathway.Science advances · 2026Article
- Molecular insights into NLRP1 Gly/N-degron recognition by CRL2Acta crystallographica. Section F, Structural biology communications · 2026Article
- A guide to mapping ubiquitin and ubiquitin-like E3 ligases to their substrates.The FEBS journal · 2026Review
- Charged molecular glue discovery enabled by targeted degron display.Nature chemical biology · 2026Article
- Advances in Decoding Bacterial N-Terminal Proteoforms: Technologies, Challenges, and Functional Insights.Microorganisms · 2026Review
- Programmable CRISPRtune dissects the transcriptional repressive activity of MeCP2.bioRxiv : the preprint server for biology · 2026Article
- Article
- TPI and GAPDH Interact with Rad9, Linking Glycolytic Enzymes to Cancer.International journal of molecular sciences · 2026Article
- Unraveling the Reverse Hofmeister Effect of 3,3',5,5'-Tetramethylbenzidine for Anion-Responsive Color-Changing Hydrogels.Chemical & biomedical imaging · 2026Article
- Article
- Deep Learning-Based Protein Half-Life Prediction for Identifying Rate-Limiting Enzymes in Metabolic Pathways to Alleviate Bottleneck Reactions.Journal of microbiology and biotechnology · 2026Article
- Mechanisms and Design Principles of Proteolysis-Targeting Chimeras and Their Emerging Applications.ACS pharmacology & translational science · 2026Review
- Prolyl hydroxylase-dependent proteolysis enables the orthogonal hypoxia responses in plants.Nature communications · 2026Article
- Attenuation of Influenza a Virus into Live Vaccines Through C-End Degrons.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Inhibition of N-Terminal Acetyltransferase C Mitigates Endoplasmic Reticulum Stress-Mediated Muscle Atrophy in Cancer Cachexia.Journal of cachexia, sarcopenia and muscle · 2026Article
- Structures of ZYG11B-EloB-EloC-substrate complex reveal mechanisms of CRL2Nature communications · 2026Article
- Programmable, target-induced fluorogenic CRISPR-tDeg platform for live-cell RNA visualization.Nucleic acids research · 2026Article
- Causal Relationship Between Serum Zinc Levels and Diabetic Kidney Disease (DKD): A Plasma Proteomics Mediation Study.Biological trace element research · 2026Article
- Functional Divergence of the Arg/N-Degron Pathway Between the CropPlant direct · 2026Article
244 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
1 author.
Funding
Abstract
This perspective is partly review and partly proposal. N-degrons and C-degrons are degradation signals whose main determinants are, respectively, the N-terminal and C-terminal residues of cellular proteins. N-degrons and C-degrons include, to varying extents, adjoining sequence motifs, and also internal lysine residues that function as polyubiquitylation sites. Discovered in 1986, N-degrons were the first degradation signals in short-lived proteins. A particularly large set of C-degrons was discovered in 2018. We describe multifunctional proteolytic systems that target N-degrons and C-degrons. We also propose to denote these systems as "N-degron pathways" and "C-degron pathways." The former notation replaces the earlier name "N-end rule pathways." The term "N-end rule" was introduced 33 years ago, when only some N-terminal residues were thought to be destabilizing. However, studies over the last three decades have shown that all 20 amino acids of the genetic code can act, in cognate sequence contexts, as destabilizing N-terminal residues. Advantages of the proposed terms include their brevity and semantic uniformity for N-degrons and C-degrons. In addition to being topologically analogous, N-degrons and C-degrons are related functionally. A proteolytic cleavage of a subunit in a multisubunit complex can create, at the same time, an N-degron (in a C-terminal fragment) and a spatially adjacent C-degron (in an N-terminal fragment). Consequently, both fragments of a subunit can be selectively destroyed through attacks by the N-degron and C-degron pathways.
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