ArticleMolecular cell2023
Ubiquitin-independent proteasomal degradation driven by C-degron pathways.
Article in Molecular cell, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
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Who cites it
60 citing papers in PubMed, 91 citations in OpenAlex.
- 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
- Hydrophobic Tag Protein Degraders: An Emerging Therapeutic Strategy for Cancer.Pharmaceuticals (Basel, Switzerland) · 2026Review
- A guide to mapping ubiquitin and ubiquitin-like E3 ligases to their substrates.The FEBS journal · 2026Review
- Exploring the sex-dependent effects of midnolin loss on hepatic transcription and chromatin accessibility.Biochemistry and biophysics reports · 2026Article
- ZNF143 suppresses mitophagy to drive MASLD progression by regulating SMURF1/TRPV1 axis.Molecular genetics and genomics : MGG · 2026Article
- Arsenic Inhibits the PA28α/β-PSMB5 Pathway Blocking Phosphorylated TFEB Degradation and Causing Lysosomal Dysfunction that Damages the Liver.Biological trace element research · 2026Article
- Herpes simplex virus type 1 interferes with signal transducer and activator of transcription 3 expression in infected mature dendritic cells.The Journal of general virology · 2026Article
- A mitochondria-driven quality control mechanism for peroxisomal membrane proteins.Nature communications · 2026Article
- A C-degron regulates Chk1 kinase by allowing stability of inactive Chk1 and by making it short- lived upon activation.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Article
- Proteasomal control of transcription factors: mechanisms, regulation and dysregulation.Cellular and molecular life sciences : CMLS · 2026Review
- Structures of the 26Science advances · 2026Article
- A near-complete map of human cytosolic degrons and their relevance for disease.Science advances · 2026Article
- Oncogenic KRAS/ERK/JUNB signaling suppresses differentiation regulator GATA6 in pancreatic cancer.The Journal of clinical investigation · 2026Article
- Hydrophobic tagging: A promising paradigm for targeted protein degradation.Cell insight · 2026Review
- Degradation Determinants Are Abundant in Human Noncanonical Proteins and Minor Annotated Isoforms.Genome biology and evolution · 2026Article
- KLHDC3 deficiency in mice reveals essential roles in development, survival, and adiposity via the DesCEND ubiquitin pathway.BMC genomics · 2026Article
- TOM20-driven E3 ligase recruitment regulates mitochondrial dynamics through PLD6.Nature chemical biology · 2026Article
- Identification of a Ubiquitin-Independent Degron by a Reporter Assay.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Proteasome Fine-Tunes the Generation of Antimicrobial Peptides.Current drug targets · 2026Review
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
Although most eukaryotic proteins are targeted for proteasomal degradation by ubiquitination, a subset have been demonstrated to undergo ubiquitin-independent proteasomal degradation (UbInPD). However, little is known about the molecular mechanisms driving UbInPD and the degrons involved. Utilizing the GPS-peptidome approach, a systematic method for degron discovery, we found thousands of sequences that promote UbInPD; thus, UbInPD is more prevalent than currently appreciated. Furthermore, mutagenesis experiments revealed specific C-terminal degrons required for UbInPD. Stability profiling of a genome-wide collection of human open reading frames identified 69 full-length proteins subject to UbInPD. These included REC8 and CDCA4, proteins which control proliferation and survival, as well as mislocalized secretory proteins, suggesting that UbInPD performs both regulatory and protein quality control functions. In the context of full-length proteins, C termini also play a role in promoting UbInPD. Finally, we found that Ubiquilin family proteins mediate the proteasomal targeting of a subset of UbInPD substrates.
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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.