Research Field

The N-degron pathway is a proteolytic system in which N-terminal residues of short-lived proteins are recognized by recognition proteins (N-recognins) as essential components of degrons, called N-degrons. N-recognins such as UBR proteins (E3 ligase) and p62 (autophagy receptor) mediate selective proteolysis of N-degron substrate by proteasomal and autophagic pathways. N-degrons can also be generated through modifications of posttranslationally exposed pro-N-degrons. ATE1 R-transferase conjugates one of the destabilizing residues, arginine (Arg), to an exposed pro-N-degron, aspartate (Asp), glutamate (Glu) or cysteine (Cys), which generates N-degron. These N-degron substrates are subsequently degraded by either proteasomal or autophagic pathway.
Our laboratory uncovered the relationship between N-degron and autophagy pathway in which arginylated substrates are recognized by p62. Based on these findings, we discover the role of N-degron pathway in cancers, neurodegenerative diseas and rare incurable diseases, and develop the targeted degradation platform targiting pathogenic proteins, Applying these findings, we suggest treatment strategies for new drug development.

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Keyword

Protein degradation, N-degron pathway, ubiquitin-proteasome system, autophagy, arginylation, Autophagy Targeted degradation