Protein palmitoylation and its pathophysiological relevance

Jin, Jiayu; Zhi, Xiuling; Wang, Xinhong; Meng, Dan

doi:10.1002/jcp.30122

Cited by 58 publications

(53 citation statements)

References 95 publications

(173 reference statements)

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“…Protein palmitoylation is less understood than other lipidations because of the lack of strong consensus sequences at modification sites [98], the scarce structural information on the interactions between palmitoyl-transferases and their substrates and the limited range of available analytical techniques. Understanding how protein palmitoylation influences the function of individual proteins in normal and tumor cells is currently an active field of research [99].…”

Section: Palmitoylationmentioning

confidence: 99%

Post-Translational Modification and Subcellular Compartmentalization: Emerging Concepts on the Regulation and Physiopathological Relevance of RhoGTPases

Navarro-Lérida

Sánchez-Álvarez

Pozo

2021

Cells

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Cells and tissues are continuously exposed to both chemical and physical stimuli and dynamically adapt and respond to this variety of external cues to ensure cellular homeostasis, regulated development and tissue-specific differentiation. Alterations of these pathways promote disease progression—a prominent example being cancer. Rho GTPases are key regulators of the remodeling of cytoskeleton and cell membranes and their coordination and integration with different biological processes, including cell polarization and motility, as well as other signaling networks such as growth signaling and proliferation. Apart from the control of GTP–GDP cycling, Rho GTPase activity is spatially and temporally regulated by post-translation modifications (PTMs) and their assembly onto specific protein complexes, which determine their controlled activity at distinct cellular compartments. Although Rho GTPases were traditionally conceived as targeted from the cytosol to the plasma membrane to exert their activity, recent research demonstrates that active pools of different Rho GTPases also localize to endomembranes and the nucleus. In this review, we discuss how PTM-driven modulation of Rho GTPases provides a versatile mechanism for their compartmentalization and functional regulation. Understanding how the subcellular sorting of active small GTPase pools occurs and what its functional significance is could reveal novel therapeutic opportunities.

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Section: Palmitoylationmentioning

confidence: 99%

Post-Translational Modification and Subcellular Compartmentalization: Emerging Concepts on the Regulation and Physiopathological Relevance of RhoGTPases

Navarro-Lérida

Sánchez-Álvarez

Pozo

2021

Cells

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“…However, compared to PPT1, PPT2 has a smaller lipid-binding pocket, which contributes to differences in their substrate specificity. PPT1 preferentially catalyzes the removal of thioester-linked long-chain fatty acids from palmitoylated substrates whereas PPT2 prefers substrate proteins to which palmitoyl-CoA is attached ( 20 ). More recently, APT1 has been reported as having thioesterase activity ( 64 ).…”

Section: Protein Palmitoylation and Depalmitoylationmentioning

confidence: 99%

“…Trafficking of membrane-associated proteins from the early secretory site to the appropriate cellular destination is, in many cases, dependent on palmitoylation (14)(15)(16). Palmitoylation also plays a critical role in regulating proteinprotein interactions, which ensures proper signal transduction (17)(18)(19)(20).…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2021

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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.

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“…In particular, reactive oxygen, nitrogen, or sulfur species are among the types of molecules that can react with thiolates to modify proteins, often via an oxidation-reduction (redox) reaction [8]. The types of reversible thiol modifications include disulfide formation [9], nitrosylation [10], sufenylation [11], glutathionylation [12], persulfidation [13], polysulfidation [13], and palmitoylation [14] (Figure 1). It is also worth noting that some of these oxidative modifications may function as intermediates to prime the cysteine for another modification, such as nitrosylation or sulfenylation, which can later be switched to glutathionylation [15].…”

Section: Introduction 1post-translational Modifications (Ptms) Of Protein Cysteine Thiolsmentioning

confidence: 99%

Stoichiometric Thiol Redox Proteomics for Quantifying Cellular Responses to Perturbations

2021

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Post-translational modifications regulate the structure and function of proteins that can result in changes to the activity of different pathways. These include modifications altering the redox state of thiol groups on protein cysteine residues, which are sensitive to oxidative environments. While mass spectrometry has advanced the identification of protein thiol modifications and expanded our knowledge of redox-sensitive pathways, the quantitative aspect of this technique is critical for the field of redox proteomics. In this review, we describe how mass spectrometry-based redox proteomics has enabled researchers to accurately quantify the stoichiometry of reversible oxidative modifications on specific cysteine residues of proteins. We will describe advancements in the methodology that allow for the absolute quantitation of thiol modifications, as well as recent reports that have implemented this approach. We will also highlight the significance and application of such measurements and why they are informative for the field of redox biology.

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Protein palmitoylation and its pathophysiological relevance

Cited by 58 publications

References 95 publications

Post-Translational Modification and Subcellular Compartmentalization: Emerging Concepts on the Regulation and Physiopathological Relevance of RhoGTPases

Post-Translational Modification and Subcellular Compartmentalization: Emerging Concepts on the Regulation and Physiopathological Relevance of RhoGTPases

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

Stoichiometric Thiol Redox Proteomics for Quantifying Cellular Responses to Perturbations

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