Protein Lipidation by Palmitoylation and Myristoylation in Cancer.

Chee Wai Fhu,Azhar Ali

doi:10.3389/fcell.2021.673647

Abstract

Posttranslational modification of proteins with lipid moieties is known as protein lipidation. The attachment of a lipid molecule to proteins endows distinct properties, which affect their hydrophobicity, structural stability, localization, trafficking between membrane compartments, and influences its interaction with effectors. Lipids or lipid metabolites can serve as substrates for lipidation, and the availability of these lipid substrates are tightly regulated by cellular metabolism. Palmitoylation and myristoylation represent the two most common protein lipid modifications, and dysregulation of protein lipidation is strongly linked to various diseases such as metabolic syndromes and cancers. In this review, we present recent developments in our understanding on the roles of palmitoylation and myristoylation, and their significance in modulating cancer metabolism toward cancer initiation and progression.

Highlights

The hallmarks of cancer are characterized by biological properties, which include continuous proliferation, resistance to apoptosis, metastasis and epithelial mesenchymal transition, sustained angiogenesis, and metabolic reprogramming (Hanahan and Weinberg, 2011)
Scientists and researchers are currently exploring the possibility of targeting protein lipidation as a paradigm for cancer therapy; there are still some unanswered questions that requires attention
Apart from DHHC enzymes, it is unclear if there are other enzymes capable of palmitoylating proteins

Summary

Introduction

The hallmarks of cancer are characterized by biological properties, which include continuous proliferation, resistance to apoptosis, metastasis and epithelial mesenchymal transition, sustained angiogenesis, and metabolic reprogramming (Hanahan and Weinberg, 2011). Structural and functional studies have shown a region in each DHHC enzyme that promotes substrate interaction and palmitoylation, suggesting unique substrate-binding preferences guiding palmitoylation of certain proteins. Subcellular localization is the first factor for palmitoylation to occur, a substrate protein has to be bound to the membrane and interacts with a DHHC enzyme.

Results

Conclusion