Protein, a functional building blocks of life, is fundamental in various aspects of organismal viability including necessary enzymatic reactions, immune surveillance, etc. Theoretically, billions of proteins present in our body are continuously synthesized and degraded to maintain the optimal balance, while, disruption in their tight balance leads to catastrophic maladies such as cancer, neurodegeneration, autoimmunity and etc.

Among the essence of proteostasis, the Proteostasis Research Institute (PSRI) focuses on protein degradation, especially the signal that determines the “live or death” of proteins. Exploring details protein degradation signal will benefit both academic and therapeutic sectors.

Proteins destined for degradation majorly follows ubiquitin-proteasome system. PSRI discovered both presence (2010) or absence (2014) of Acetyl-moiety (CH3CO) at the N-terminus of proteins can trigger their degradation in a condition dependent manner (named Ac/N-degron and MetΦ/N-degron pathway). Sequentially, correlation between Ac/N-degron pathway and blood pressure regulation in mammalian system was elucidated (2015). Furthermore, presence of N-terminal formyl-methionine-initiated protein translation, which overturns the current understanding, and their function as a protein degradation signal in eukaryotic system (named fMet/N-degron pathway) were identified. (2018) Above findings were featured in ‘Cell’ and ‘Science’, the most prestigious and globally approved academic journals.

While researching to identify new degradation signals, the Lab also works to develop new drugs based on the research outcomes generated over the years on protein degradation. The Lab is fully equipped with the experimentation devices needed to successfully carry out research initiatives to this end. Lab members proudly point out that they are able to simultaneously conduct a wide array of experiments – from discovering novel phenomena through in vitro and yeast testing, to revalidating the target phenomena through mammalian cell testing and expanding these phenomena through animal models & drug development.

“We will delve even deeper into the physiological implications of the degradation signals we have discovered so far”, Professor Hwang noted, and added “we will leverage these signals to engineer new and innovative drugs with novel content and formulations”.