ArticleScientific reports2014
A neurostimulant para-chloroamphetamine inhibits the arginylation branch of the N-end rule pathway.
Article in Scientific reports, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 23 citations in OpenAlex.
- RGS proteins and cardiovascular Angiotensin II Signaling: Novel opportunities for therapeutic targeting.Biochemical pharmacology · 2023Review
- Signaling Pathways Regulated by UBR Box-Containing E3 Ligases.International journal of molecular sciences · 2021Review
- 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
- Assessment of common housekeeping genes as reference for gene expression studies using RT-qPCR in mouse choroid plexus.Scientific reports · 2021Article
- Unveiling synapse pathology in spinal bulbar muscular atrophy by genome-wide transcriptome analysis of purified motor neurons derived from disease specific iPSCs.Molecular brain · 2020Article
- Regulating the regulators: Epigenetic, transcriptional, and post-translational regulation of RGS proteins.Cellular signalling · 2018Review
- Docosahexaenoic acid-mediated protein aggregates may reduce proteasome activity and delay myotube degradation during muscle atrophy in vitro.Experimental & molecular medicine · 2017Article
- The arginylation branch of the N-end rule pathway positively regulates cellular autophagic flux and clearance of proteotoxic proteins.Autophagy · 2016Article
- R4 Regulator of G Protein Signaling (RGS) Proteins in Inflammation and Immunity.The AAPS journal · 2016Review
- Pharmacological Modulation of the N-End Rule Pathway and Its Therapeutic Implications.Trends in pharmacological sciences · 2015Review
- The therapeutic potential of targeting cardiac RGS4.Therapeutic advances in cardiovascular diseaseReview
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In the arginylation branch of the N-end rule pathway, unacetylated N-terminal destabilizing residues function as essential determinants of protein degradation signals (N-degron). Here, we show that a neurostimulant, para-chloroamphetamine (PCA), specifically inhibits the Arg/N-end rule pathway, delaying the degradation of its artificial and physiological substrates, including regulators of G protein signaling 4 (RGS4), in vitro and in cultured cells. In silico computational analysis indicated that PCA strongly interacts with both UBR box and ClpS box, which bind to type 1 and type 2 N-degrons, respectively. Moreover, intraperitoneal injection of PCA significantly stabilized endogenous RGS4 proteins in the whole mouse brain and, particularly, in the frontal cortex and hippocampus. Consistent with the role of RGS4 in G protein signaling, treatment with PCA impaired the activations of GPCR downstream effectors in N2A cells, phenocopying ATE1-null mutants. In addition, levels of pathological C-terminal fragments of TDP43 bearing N-degrons (Arg208-TDP25) were significantly elevated in the presence of PCA. Thus, our study identifies PCA as a potential tool to understand and modulate various pathological processes regulated by the Arg/N-end rule pathway, including neurodegenerative processes in FTLD-U and ALS.
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