Palmitoylated proteins

Palmitoylated proteins are a diverse group of proteins that undergo a reversible post-translational modification involving the covalent attachment of a 16-carbon palmitic acid to cysteine residues. This modification, known as S-palmitoylation, is mediated by the ZDHHC family of palmitoyltransferases and is unique among lipid modifications due to its reversibility, which is managed by acyl-protein thioesterases (APTs) [1][2]. Palmitoylation serves as a molecular switch that regulates protein membrane affinity, subcellular localization, and interaction with other signaling partners [2]. It is essential for the proper functioning of key proteins such as Ras GTPases, G proteins, and various ion channels and receptors [3]. Dysregulation of the palmitoylation state is a hallmark of several diseases, including various cancers where it facilitates oncogenic signaling, and neurodegenerative disorders like Huntington’s disease where it affects protein stability and trafficking [4][5]. While palmitoylated proteins as a class are not a single drug target, the enzymes that control this modification (ZDHHCs and APTs) are actively being explored as therapeutic nodes [6]. Current pharmacological interventions often involve small molecule inhibitors like 2-bromopalmitate or more specific APT inhibitors like Palmostatin B, though systemic toxicity and lack of specificity remain significant hurdles [4][6].

Other names

S-palmitoylated proteinsS-acylated proteinsPalmitoylated substrates

Inhibition of protein acyltransferases (ZDHHC family) to prevent palmitate attachment or inhibition of acyl-protein thioesterases (APTs) to prevent depalmitoylation.