|Title||Identification of new protein function that activates the harmful protein dissolution in the cell|
- Identify the mechanism to promote the waste protein dissolution in the cell by p62 protein
- Expected to develop treatment for neurodegenerative diseases, cancer and cardiovascular diseases by removing cytoxic cell protein
A domestic research team and research team from University of Pittsburgh presented a new way for the treatment of cancer, neurodegenerative diseases and cardiovascular diseases by identifying a new mechanism to activate protein dissolution.
Korea Research Institute of Bioscience & Biotechnology (President Chang Kyu-tae, KRIBB) Anticancer Agent Research Center team led by Dr. Kim Bo-yeon (corresponding author: Kim Bo-yeon, joint lead authors: Cha Hyeon-joo, Yoo Ji-eun, Kim Jeongki) and Seoul National University team led by professor Kwon Yong-tae (corresponding author: Kwon Yong-tae, joint lead author: Lee Soo-heyon), University of Pittsburgh team led by professor Xiang-Qun Xie (corresponding author: Xiang-Qun Xie, joint lead authors Zhiwei Feng, Peng Yang) conducted this study jointly with the support of Creative Convergence Research Project (CAP) by the Ministry of Science and ICT and National Research Council of Science & Technology. The study was published on the online version of Nature Communications, IF 12.124, a world’s renowned journal in biology as of July 25 (on July 26, Korean Standard Time).
The research is the follow-up to the research outcome published in Nature Cell Biology (IF 20.060) in 2015. The previous research identified a new mechanism to promote the dissolution of toxic protein generated when cells are under stress while the recent study identified a function of protein that can activate the waste protein dissolution and new controlling mechanism in the body to keep healthy cells in normal state.
So far, ubiqutine-proteasome system and autophagy system have been known as major mechanism for protein dissolution and to play the role in vitality and keeping homeostasis of living organism under stress. But the research team provided answer to the question on “when how do these two systems control mutually”.
If the protein denaturation waste is accumulated due to aging, genetic mutation and stress in the cells, cells are damaged as differentiated cells such as neural cells and muscle cells are unable to dilute protein waste through cell division, which could cause cancer (alcoholic hepatitis and liver cancer), degenerative brain diseases (Huntington’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, Creutzfeldt-Jakob disease/human mad cow disease) or cardiac hypertrophy.
Under this circumstance, it was found that p62 (Sequestosome-1) which has been known to transfer protein aggregate and waste in the cell has the function to increase autophagy under stress. It was also found that the mechanism is interrelated with proteasome system, which is the major route for protein dissolution.
So far, the relationship between autophagy vitalization and proteasome vitalization to handle protein aggregates has not been known. However, this study found that if the proteasome path is blocked or protein aggregate is accumulated, the autophagy path is activated through p62 protein to dissolve waste protein. Therefore, the study can be applied to the development of treatment for aging and metabolism related diseases including cancer as it is possible to activate the processing of protein aggregates accumulated in the cell by controlling p62 and relevant proteins.
The research team will focus on securing source technology to remove Huntington protein aggregate, which is the cause of Huntington’s disease from cultivated cell using low molecular compounds and developing new cancer treatment.
Dr. Kim Bo-yeon, who is responsible for this study, said “we found the fact that it is very important to activate and control proteasome and autophagy to improve the effectiveness of treating metabolism related diseases such as cancer, immune system related diseases and neurodegenerative diseases. If the combination therapy with proteasome inhibitor is developed by identifying a new low molecule compound that can control autophagy in the future we may contribute to the improvement of treatment efficiency for incurable metabolic diseases such as cancer, diabetes, inflammatory diseases, neurodegenerative diseases and cardiovascular diseases”.