ArticleThe Journal of biological chemistry2009
Ubiquitylation on canonical and non-canonical sites targets the transcription factor neurogenin for ubiquitin-mediated proteolysis.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 80 citations in OpenAlex.
- Mechanisms and Design Principles of Proteolysis-Targeting Chimeras and Their Emerging Applications.ACS pharmacology & translational science · 2026Review
- Modulation of the tumor microenvironment by the ubiquitin-proteasome system in colorectal cancer.Journal of translational medicine · 2025Review
- Noncanonical and reversible cysteine ubiquitination prevents the overubiquitination of PEX5 at the peroxisomal membrane.PLoS biology · 2024Article
- Structural and functional validation of a highly specific Smurf2 inhibitor.Protein science : a publication of the Protein Society · 2024Article
- Catalysis of non-canonical protein ubiquitylation by the ARIH1 ubiquitin ligase.The Biochemical journal · 2023Article
- Arginine 65 methylation of Neurogenin 3 by PRMT1 is required for pancreatic endocrine development of hESCs.Experimental & molecular medicine · 2023Article
- Proteomic approaches to study ubiquitinomics.Biochimica et biophysica acta. Gene regulatory mechanisms · 2023Review
- An expanded lexicon for the ubiquitin code.Nature reviews. Molecular cell biology · 2023Review
- Thioester and Oxyester Linkages in the Ubiquitin System.Methods in molecular biology (Clifton, N.J.) · 2023Review
- Deciphering non-canonical ubiquitin signaling: biology and methodology.Frontiers in molecular biosciences · 2023Review
- Post-translational modifications and immune responses in liver cancer.Frontiers in immunology · 2023Review
- Non-lysine ubiquitylation: Doing things differently.Frontiers in molecular biosciences · 2022Review
- The linear ubiquitin chain assembly complex (LUBAC) generates heterotypic ubiquitin chains.eLife · 2021Article
- Role of Proteasomes in Inflammation.Journal of clinical medicine · 2021Review
- The Ubiquitin-Proteasome System in Immune Cells.Biomolecules · 2021Review
- Alpha-Synuclein Post-translational Modifications: Implications for Pathogenesis of Lewy Body Disorders.Frontiers in aging neuroscience · 2021Review
- New Insights Into the Intricacies of Proneural Gene Regulation in the Embryonic and Adult Cerebral Cortex.Frontiers in molecular neuroscience · 2021Review
- Role of Host-Mediated Post-Translational Modifications (PTMs) in RNA Virus Pathogenesis.International journal of molecular sciences · 2020Review
- Fbxo9 functions downstream of Sox10 to determine neuron-glial fate choice in the dorsal root ganglia through Neurog2 destabilization.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Cytochrome P450 endoplasmic reticulum-associated degradation (ERAD): therapeutic and pathophysiological implications.Acta pharmaceutica Sinica. B · 2020Review
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Polyubiquitylation targets multiple proteins for degradation by the proteasome. Typically, the first ubiquitin is linked to lysine residues in the substrate for degradation via an isopeptide bond, although rarely ubiquitin linkage to the N-terminal residue has also been observed. We have recently shown that Neurogenin (NGN), a basic helix-loop-helix transcription factor that plays a central role in regulating neuronal differentiation, is degraded by ubiquitin-mediated proteolysis. We have taken a biochemical and mutagenesis approach to investigate sites of ubiquitylation of NGN, initially using extracts of eggs from the frog Xenopus laevis as a source of ubiquitylation and degradation components. NGN can be targeted for destruction by ubiquitylation via lysines or the N terminus. However, we see that a modified NGN, where canonical lysine ubiquitylation and N-terminally linked ubiquitylation are prevented, is nevertheless ubiquitylated and degraded by the proteasome. We show that polyubiquitin chains covalently attach to non-canonical cysteine residues in NGN, and these non-canonical linkages alone are capable of targeting NGN protein for destruction. Importantly, canonical and non-canonical ubiquitylation occurs simultaneously in the native protein and may differ in importance for driving degradation in interphase and mitosis. We conclude that native NGN is ubiquitylated on multiple canonical and non-canonical sites by cellular ubiquitin ligases, and all types of linkage can contribute to protein turnover.
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