Palmitoylated substrate proteins

Palmitoylated substrate proteins are a diverse group of proteins that undergo S-palmitoylation, a reversible post-translational modification involving the attachment of a 16-carbon palmitate fatty acid to cysteine residues via a thioester bond (Resh, 2016). This modification is a key regulator of protein hydrophobicity, facilitating membrane association, subcellular trafficking, and the organization of proteins into specialized membrane domains like lipid rafts (Main and Fuller, 2018). Thousands of proteins, including Ras GTPases, G-protein coupled receptors, and synaptic scaffold proteins, rely on palmitoylation for their proper function and localization (Chamberlain and Shipston, 2015). Dysregulation of the palmitoylation status of these substrates is linked to various pathologies, such as oncogenic signaling in cancer and synaptic dysfunction in neurodegenerative diseases like Huntington's and Alzheimer's (Chen et al., 2021). While the substrates themselves are the functional units, therapeutic intervention typically targets the enzymes responsible for the addition (DHHC palmitoyltransferases) or removal (acyl-protein thioesterases) of the palmitate group (Ko and Dixon, 2018). Small molecules like 2-bromopalmitate and various APT inhibitors are used in research to modulate these processes, though clinical application is challenged by the need for high specificity within the vast palmitoylome.

Other names

S-palmitoylated proteinsPalmitoylated proteinsS-acylated proteinsPalmitoylome

Inhibition of DHHC palmitoyltransferases or acyl-protein thioesterases (APTs) to modulate the palmitoylation status of substrate proteins.