ArticleAutophagy2016
The arginylation branch of the N-end rule pathway positively regulates cellular autophagic flux and clearance of proteotoxic proteins.
Article in Autophagy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 25 citations in OpenAlex.
- tRNAmicroPublication biology · 2024Article
- Article
- The Antipsychotic Drug Clozapine Suppresses the RGS4 Polyubiquitylation and Proteasomal Degradation Mediated by the Arg/N-Degron Pathway.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2021Article
- Arginyltransferase (Ate1) regulates the RGS7 protein level and the sensitivity of light-evoked ON-bipolar responses.Scientific reports · 2021Article
- CHIP-mediated hyperubiquitylation of tau promotes its self-assembly into the insoluble tau filaments.Chemical science · 2021Article
- Arginylation Regulates G-protein Signaling in the Retina.Frontiers in cell and developmental biology · 2021Article
- Docosahexaenoic Acid, a Potential Treatment for Sarcopenia, Modulates the Ubiquitin-Proteasome and the Autophagy-Lysosome Systems.Nutrients · 2020Review
- tRNACell chemical biology · 2020Article
- Article
- Protein arginylation of cytoskeletal proteins in the muscle: modifications modifying function.American journal of physiology. Cell physiology · 2019Review
- New beginnings and new ends: methods for large-scale characterization of protein termini and their use in plant biology.Journal of experimental botany · 2019Review
- Detecting Modifications in Proteomics Experiments with Param-Medic.Journal of proteome research · 2019Article
- Degradation or aggregation: the ramifications of post-translational modifications on tau.BMB reports · 2018Review
- Protein arginylation targets alpha synuclein, facilitates normal brain health, and prevents neurodegeneration.Scientific reports · 2017Article
- The Protective Roles of ROS-Mediated Mitophagy onOxidative medicine and cellular longevity · 2016Article
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The N-terminal amino acid of a protein is an essential determinant of ubiquitination and subsequent proteasomal degradation in the N-end rule pathway. Using para-chloroamphetamine (PCA), a specific inhibitor of the arginylation branch of the pathway (Arg/N-end rule pathway), we identified that blocking the Arg/N-end rule pathway significantly impaired the fusion of autophagosomes with lysosomes. Under ER stress, ATE1-encoded Arg-tRNA-protein transferases carry out the N-terminal arginylation of the ER heat shock protein HSPA5 that initially targets cargo proteins, along with SQSTM1, to the autophagosome. At the late stage of autophagy, however, proteasomal degradation of arginylated HSPA5 might function as a critical checkpoint for the proper progression of autophagic flux in the cells. Consistently, the inhibition of the Arg/N-end rule pathway with PCA significantly elevated levels of MAPT and huntingtin aggregates, accompanied by increased numbers of LC3 and SQSTM1 puncta. Cells treated with the Arg/N-end rule inhibitor became more sensitized to proteotoxic stress-induced cytotoxicity. SILAC-based quantitative proteomics also revealed that PCA significantly alters various biological pathways, including cellular responses to stress, nutrient, and DNA damage, which are also closely involved in modulation of autophagic responses. Thus, our results indicate that the Arg/N-end rule pathway may function to actively protect cells from detrimental effects of cellular stresses, including proteotoxic protein accumulation, by positively regulating autophagic flux.
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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.