PTM manipulation programs for anti-cancer therapy at MCCB
Proteins often undergo a variety of chemical modifications, so-called "post-translational modification" or "PTM", after translation process. The type of PTMs involves phosphorylation, acetylation, methylation, ubiquitination, and so on. It is well established that PTMs play important roles in modulation of the protein function inside the cell, and therefore it is not surprising that aberrations in the PTM process are frequently associated with many important human diseases including cancer. Therefore, development of a chemical means that can selectively control the PTM process is considered as a promising strategy for development of a novel anti-cancer agent. In this regard, the MCCB laboratory has recently launched a number of research projects aiming to propose new approaches for selective PTM control as means of effective treatment of cancer.
Project #1. Proximity-based selective PTM control
Researchers: Do Young Kim (김도영), Ji Won Kim (yeon Yeom (염수연), Jimin Park (박지민)
The localization of protein partners in proximity is a fundamental mechanism of, arguably, the majority of cellular processes for acceleration of chemical reactions, cooperative action of macromolecular complexes, precise signal transduction, and so on. Inspired by such a natural mechanism, there have been great efforts to mimic the proximity-based control of cellular processes with small molecules and notable successes have been reported. The MCCB laboratory is particularly interested in proximity-based selective ubiquitination as well as acetylation of various oncogenic and tumor-suppressing proteins. Ubiquitination promotes proteasome-based degradation of the ubiquitinated protein. The role of protein acetylation is diverse, and some tumor-suppressing proteins such as p53 are known to become more stable upon acetylation. Thus, we anticipate that development of selective chemical means to manipulate these PTMs can provide with unprecedented, effective solutions for cancer therapy.
Edited in Feb, 2023