Title:Integral Membrane Protein Degradation: A Novel Paradigm by PROTAC Technology
Volume: 2
Author(s): Priyanka Ray*, Aditi Nayak and Saini Setua
Affiliation:
- Department of Pharmacy, Guru Nanak Institute of Pharmaceutical Science & Technology, Sodepur, Kolkata-114, India
Keywords:
Proteolysis, Integral membrane protein, PROTAC, Ubiquitin ligases, Protein degradation, Autophagy.
Abstract: Integral membrane proteins are attractive targets for therapeutic intervention due to their crucial roles in cellular functions and their involvement in
various diseases. However, targeting these proteins for degradation has posed significant challenges due to their complex structures and diverse
functions. The emergence of proteolysis-targeting chimeras (PROTAC) represents a groundbreaking paradigm shift in drug development, offering
a novel approach to address the degradation of integral membrane proteins. This review explores the innovative application of PROTAC
technology in inducing the degradation of integral membrane proteins. PROTACs are molecules that have two roles: they bring together specific
target proteins and E3 ubiquitin ligases, which help with ubiquitination and the degradation of proteins by proteasomes. As PROTACs are made up
of separate parts, they can be put together to make custom molecules that can target difficult targets, such as integral membrane proteins. This
review covers recent developments and advancements in the design and optimisation of PROTACs tailored for integral membrane protein
degradation. Furthermore, it also discusses the problems that come up when trying to target membrane proteins and how PROTACs solve these
problems by using ligands that can pass cell membranes and specifically interact with target proteins. It delves into the potential therapeutic
implications of degrading integral membrane proteins using PROTACs and elucidates the impact of this novel approach in treating diseases that
involve aberrant membrane protein expression or function by highlighting specific examples and case studies.
