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Review
. 2021 May 20:9:673647.
doi: 10.3389/fcell.2021.673647. eCollection 2021.

Protein Lipidation by Palmitoylation and Myristoylation in Cancer

Chee Wai Fhu  1 , Azhar Ali  1
Affiliations
Review

Protein Lipidation by Palmitoylation and Myristoylation in Cancer

Chee Wai Fhu et al. Front Cell Dev Biol. .

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.

Keywords: cancer; depalmitoylation; metabolism; myristoylation; palmitoylation; protein lipidation.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Mechanism of action of palmitoyl S-acyltransferase (PAT). Briefly, Asp–His–His–Cys (DHHC) binds to palmitoyl-coenzyme A (CoA) located at the membrane and transfers a fatty acyl chain to the targeted substrate protein releasing CoA.
FIGURE 2
FIGURE 2
Mechanism of action of acyl-protein thioesterase (APT). APT binds to a specific acylated substrate and cleaves off the fatty acyl chain located on the sulfur atom on the cysteine residue linked via thioester bond.
FIGURE 3
FIGURE 3
Types of myristoylation. (A) Schematic illustration of steps involved in cotranslational myristoylation. During cotranslational myristoylation, the myristoyl group is added to the N-terminal glycine residue following cleavage of the N-terminal methionine residue on the growing polypeptide chain. (B) Posttranslational myristoylation normally occurs following caspase cleavage event, resulting in the exposure of internal glycine residue, which allows myristic acid addition.
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