Function of Protein S-Palmitoylation in Immunity and Immune-Related Diseases

Abstract

Protein S-palmitoylation is a covalent and reversible lipid modification that specifically targets cysteine residues within many eukaryotic proteins. In mammalian cells, the ubiquitous palmitoyltransferases (PATs) and serine hydrolases, including acyl protein thioesterases (APTs), catalyze the addition and removal of palmitate, respectively. The attachment of palmitoyl groups alters the membrane affinity of the substrate protein changing its subcellular localization, stability, and protein-protein interactions. Forty years of research has led to the understanding of the role of protein palmitoylation in significantly regulating protein function in a variety of biological processes. Recent global profiling of immune cells has identified a large body of S-palmitoylated immunity-associated proteins. Localization of many immune molecules to the cellular membrane is required for the proper activation of innate and adaptive immune signaling. Emerging evidence has unveiled the crucial roles that palmitoylation plays to immune function, especially in partitioning immune signaling proteins to the membrane as well as to lipid rafts. More importantly, aberrant PAT activity and fluctuations in palmitoylation levels are strongly correlated with human immunologic diseases, such as sensory incompetence or over-response to pathogens. Therefore, targeting palmitoylation is a novel therapeutic approach for treating human immunologic diseases. In this review, we discuss the role that palmitoylation plays in both immunity and immunologic diseases as well as the significant potential of targeting palmitoylation in disease treatment.

Protein S-palmitoylation regulates different stages of meiosis inSchizosaccharomyces pombe

“…Although changes in the global protein S-palmitoylation pattern have been associated with different physiological states such as cellular differentiation ( Zhang & Hang, 2017 ) and pathological conditions ( Zhang et al, 2021 ), the detailed molecular mechanisms of how protein S-palmitoylation regulates these processes remained to be defined.…”

“…Although changes in the global protein S-palmitoylation pattern have been associated with different physiological states such as cellular differentiation (Zhang & Hang, 2017) and pathological conditions (Zhang et al, 2021), the detailed molecular mechanisms of how protein S-palmitoylation regulates these processes remained to be defined. In an earlier study of protein S-palmitoylation in S. pombe, using the synchronized meiosis induced from pat1-114 diploid cells, Zhang et al (2013) demonstrated that the global protein S-palmitoylation pattern was significantly altered and shaped by varying Erf2 palmitoylacyltransferase activity during meiosis.…”

Recombinant AMA1 Virus-like Particle Antigen for Serodiagnosis of Toxoplasma gondii Infection

“…However, the last cysteine residue where palmitoylation occurs in T. gondii is not conserved across multiple members of the Plasmodium spp., including P. berghei [ 40 ]. Investigating whether this difference accounts for the lack of cross-species interaction is beyond the scope of this study, but given that cysteine palmitoylation has a profound effect on immune-related aspects [ 41 , 42 ], it would be an interesting area to study in the future. Interestingly, human sample antibody responses were substantially lower than those elicited by murine sera.…”

Positive Regulation of the Antiviral Activity of Interferon-Induced Transmembrane Protein 3 by S-Palmitoylation

“…However, this approach has the defects of limited sensitivity and poor security. New technologies, such as acy-biotinyl exchange and click-chemistry that allow S-palmitoylation sites to be experimentally-determined have greatly promoted the study of this lipid modification ( 112 ). Currently, the research progresses of IFITM3 S-palmitoylation were listed in Table 1 .…”