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Chemogenetic Regulation in Reprogrammed Stem Cell-derived Precursor Cells in Treating Neurodegenerative Diseases

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The N-degron pathway: From basic science to therapeutic applications.

Ah Jung Heo¹, Su Bin Kim¹, Yong Tae Kwon²

¹Cellular Degradation Biology Center and Department of Biomedical Sciences, College of Medicine, Seoul National University, Seoul 03080, Republic of Korea.

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Summary

The N-degron pathway uses N-terminal amino acids to control protein lifespan, linking to the ubiquitin-proteasome system or autophagy-lysosome system for degradation. This system targets various cellular components, offering therapeutic potential.

Keywords:

Autophagy-lysosome system E3 ligase N-recognin Nt-arginylation The N-degron pathway Ubiquitin-proteasome system

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Area of Science:

Cellular Biology
Molecular Biology
Biochemistry

Background:

The N-degron pathway regulates protein half-lives via N-terminal amino acids.
N-degrons are recognized by N-recognins, linking to the ubiquitin-proteasome system (UPS) or autophagy-lysosome system (ALS).

Purpose of the Study:

To discuss the components, regulation, and functions of N-degron pathways.
To emphasize the mechanisms and therapeutic applications of Arg/N-degrons and N-recognins.

Main Methods:

Review of existing literature on N-degron pathways.
Analysis of the roles of N-recognins in protein degradation.

Main Results:

The Arg/N-degron pathway targets N-terminal arginine for degradation via UPS or ALS.
Crosstalk between UPS and ALS involves ubiquitin code reprogramming.
Eukaryotic cells utilize diverse N-degrons for degradation of all 20 amino acids.

Conclusions:

N-degron pathways are crucial for cellular protein homeostasis.
Understanding Arg/N-degrons and their N-recognins offers therapeutic avenues.