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Review
. 2021 Dec;288(24):7043-7059.
doi: 10.1111/febs.15728. Epub 2021 Feb 12.

Protein cysteine palmitoylation in immunity and inflammation

Hening Lin  1
Affiliations
Review

Protein cysteine palmitoylation in immunity and inflammation

Hening Lin. FEBS J. 2021 Dec.

Abstract

Protein cysteine palmitoylation, or S-palmitoylation, has been known for about 40 years, and thousands of proteins in humans are known to be modified. Because of the large number of proteins modified, the importance and physiological functions of S-palmitoylation are enormous. However, most of the known physiological functions of S-palmitoylation can be broadly classified into two categories, neurological or immunological. This review provides a summary on the function of S-palmitoylation from the immunological perspective. Several important immune signaling pathways are discussed, including STING, NOD1/2, JAK-STAT in cytokine signaling, T-cell receptor signaling, chemotactic GPCR signaling, apoptosis, phagocytosis, and endothelial and epithelial integrity. This review is not meant to be comprehensive, but rather focuses on specific examples to highlight the versatility of palmitoylation in regulating immune signaling, as well as the potential and challenges of targeting palmitoylation to treat immune diseases.

Keywords: NOD1; STAT3; STING; ZDHHC; cysteine palmitoylation; cytokine signaling; depalmitoylase; inflammation; lipid raft; palmitoyltransferase.

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Conflict of interest statement

Conflict of Interest: HL is a founder and consultant for Sedec Therapeutics.

Figures

Figure 1.
Figure 1.
Reversible protein cysteine palmitoylation catalyzed by palmitoyltransferases (ZDHHCs) and depalmitoylases (APT1/2, ABHD10, and ABHD17).
Figure 2.
Figure 2.
The role of palmitoylation in STING (A), NOD1/2 (B), and TLR (C) signaling pathways. Steps involved in the signaling pathways are listed and the steps that are known to be affected by S-palmitoylation are indicated.
Figure 3.
Figure 3.
Palmitoylation-depalmitoylation cycle of CD36 (A) and STAT3 (B). In A, the steps involved in CD36 trafficking are listed to show how the cycle promote the function of CD36 in fatty acid uptake. In B, the steps involved in STAT3 activation and signaling outcomes are listed. The net result of the STAT3 palmitoylation-depalmitoylation cycle is the differentiation of Th17 and inflammation.
Figure 4.
Figure 4.
Multiple proteins in the TCR signaling pathway are regulated by palmitoylation. Key components involved in the signaling pathway are shown. Palmitoylation is indicated by red squiggly lines.
See this image and copyright information in PMC

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