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Bioprocess 2023
蛋白质S-棕榈酰化在T细胞信号传导中的研究进展
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Abstract:
蛋白质S-棕榈酰化是一种高度动态的翻译后脂质化修饰，由DHHC蛋白家族催化，在调节蛋白质定位、稳定性和细胞内转运等方面发挥重要作用。近年来，随着T细胞免疫疗法的兴起，对于T细胞信号通路的研究也愈发深入。大量证据表明，T细胞活化过程中，有很多关键信号分子是S-棕榈酰化的，它们的稳定表达和质膜定位对于免疫信号的传递是必需的。因此，本文总结了DHHC蛋白家族和蛋白质S-棕榈酰化的机制，并基于S-棕榈酰化在T细胞信号传导中的不同作用，分析了靶向S-棕榈酰化治疗免疫疾病的潜力和挑战。
Protein S-palmitoylation is a highly dynamic post-translational lipid modification catalyzed by the DHHC protein family which plays an important role in regulating pro-tein localization, stability and intracellular translocation. In recent years, there has been a surge of interest in T-cell-based immunotherapy, leading to a deeper investigation of T-cell signaling path-ways. A large amount of evidence indicates that many pivotal signaling molecules involved in T-cell activation are modified by S-palmitoylation, which is essential for their stable expression and plas-ma membrane localization, and thus for proper immune signaling. Therefore, in this review, we summarize the DHHC protein family and the mechanism of protein S-palmitoylation, and analyze the potential and challenges of targeting S-palmitoylation for immune diseases based on the differ-ent roles of S-palmitoylation in T-cell signaling transduction.
| [1] | Bijlmakers, M.J. (2009) Protein Acylation and Localization in T Cell Signaling. Molecular Membrane Biology, 26, 93-103. https://doi.org/10.1080/09687680802650481 |
| [2] | Kabouridis, P.S., Magee, A.I. and Ley, S.C. (1997) S-acylation of LCK Protein Tyrosine Kinase Is Essential for Its Signalling Function in T Lymphocytes. The EMBO Journal, 16, 4983-4998. https://doi.org/10.1093/emboj/16.16.4983 |
| [3] | Kosugi, A., Hayashi, F., Liddicoat, D.R., et al. (2001) A Pivotal Role of Cysteine 3 of Lck Tyrosine Kinase for Localization to Glycolipid-Enriched Microdomains and T Cell Activation. Immunology Letters, 76, 133-138.
https://doi.org/10.1016/S0165-2478(01)00174-2 |
| [4] | Kwong, J. and Lublin, D.M. (1995) Amino-Terminal Palmi-tate or Polybasic Domain Can Provide Required Second Signal to Myristate for Membrane Binding of P56lck. Biochemi-cal and Biophysical Research Communications, 207, 868-876. https://doi.org/10.1006/bbrc.1995.1266 |
| [5] | Yurchak, L.K. and Sefton, B.M. (1995) Palmitoylation of either Cys-3 or Cys-5 Is Required for the Biological Activity of the Lck Tyrosine Protein Kinase. Molecular and Cellular Biology, 15, 6914-6922.
https://doi.org/10.1128/MCB.15.12.6914 |
| [6] | Gauthaman, A., Jacob, R., Pasupati, S., et al. (2022) Novel Pep-tide-Based Inhibitor for Targeted Inhibition of T Cell Function. Journal of Cell Communication and Signaling, 16, 349-359. https://doi.org/10.1007/s12079-021-00660-0 |
| [7] | Sato, I., Obata, Y., Kasahara, K., et al. (2009) Differ-ential Trafficking of Src, Lyn, Yes and Fyn Is Specified by the State of Palmitoylation in the SH4 Domain. Journal of Cell Science, 122, 965-975. https://doi.org/10.1242/jcs.034843 |
| [8] | West, S.J., Boehning, D. and Akimzhanov, A.M. (2022) Regulation of T Cell Function by Protein S-acylation. Frontiers in Physiology, 13, Article 2404. https://doi.org/10.3389/fphys.2022.1040968 |
| [9] | Schultz, A., Schnurra, M., El Bizri, A., et al. (2022) A Cysteine Residue within the Kinase Domain of Zap70 Regulates Lck Activity and Proximal TCR Signaling. Cells, 11, Article 2723. https://doi.org/10.3390/cells11172723 |
| [10] | Martinez-Florensa, M., Garcia-Blesa, A., Yélamos, J., et al. (2011) Serine Residues in the LAT Adaptor Are Essential for TCR-Dependent Signal Transduction. Journal of Leukocyte Biol-ogy, 89, 63-73. https://doi.org/10.1189/jlb.0509342 |
| [11] | Shim, E.K., Jung, S.H. and Lee, J.R. (2011) Role of Two Adaptor Molecules SLP-76 and LAT in the PI3K Signaling Pathway in Activated T Cells. The Journal of Immunology, 186, 2926-2935. https://doi.org/10.4049/jimmunol.1001785 |
| [12] | Zhang, W.G., Trible, R.P. and Samelson, L.E. (1998) LAT Palmitoylation: Its Essential Role in Membrane Microdomain Targeting and Tyrosine Phosphorylation dur-ing T Cell Activation. Immunity, 9, 239-246.
https://doi.org/10.1016/S1074-7613(00)80606-8 |
| [13] | Morrison, E., Wegner, T., Zucchetti, A.E., et al. (2020) Dy-namic Palmitoylation Events Following T-Cell Receptor Signaling. Communications Biology, 3, Article No. 368. https://doi.org/10.1038/s42003-020-1063-5 |
| [14] | Hundt, M., Tabata, H., Jeon, M.S., et al. (2006) Impaired Activa-tion and Localization of LAT in Anergic T Cells as a Consequence of a Selective Palmitoylation Defect. Immunity, 24, 513-522.
https://doi.org/10.1016/j.immuni.2006.03.011 |
| [15] | Trebak, M. and Kinet, J.P. (2019) Calcium Signalling in T Cells. Nature Reviews Immunology, 19, 154-169.
https://doi.org/10.1038/s41577-018-0110-7 |
| [16] | Fredericks, G.J., Hoffmann, F.W., Rose, A.H., et al. (2014) Sta-ble Expression and Function of the Inositol 1,4,5-Triphosphate Receptor Requires Palmitoylation by a DHHC6/Selenoprotein K Complex. Proceedings of the National Academy of Sciences, 111, 16478-16483. https://doi.org/10.1073/pnas.1417176111 |
| [17] | Lin, H.N. (2021) Protein Cysteine Palmitoylation in Immunity and Inflammation. The FEBS Journal, 288, 7043-7059.
https://doi.org/10.1111/febs.15728 |
| [18] | Yao, H., Lan, J., Li, C.S., et al. (2019) Inhibiting PD-L1 Palmitoylation Enhances T-Cell Immune Responses against Tumours. Nature Biomedical Engineering, 3, 306-317. https://doi.org/10.1038/s41551-019-0375-6 |
| [19] | Yang, Y., Hsu, J.M., Sun, L., et al. (2019) Palmitoylation Stabi-lizes PD-L1 to Promote Breast Tumor Growth. Cell Research, 29, 83-86. https://doi.org/10.1038/s41422-018-0124-5 |
| [20] | Zmuda, F. and Chamberlain, L.H. (2020) Regulatory Effects of Post-Translational Modifications on zDHHC S-Acyltransferases. Journal of Biological Chemistry, 295, 14640-14652. https://doi.org/10.1074/jbc.REV120.014717 |
| [21] | Jiang, H., Zhang, X.Y., Chen, X., et al. (2018) Protein Lipidation: Occurrence, Mechanisms, Biological Functions, and Enabling Technologies. Chemical Reviews, 118, 919-988. https://doi.org/10.1021/acs.chemrev.6b00750 |
| [22] | Yao, H., Li, C.S., He, F., et al. (2021) A Peptidic Inhibitor for PD-1 Palmitoylation Targets Its Expression and Functions. RSC Chemical Biology, 2, 192-205. https://doi.org/10.1039/D0CB00157K |
| [23] | Linder, M.E. and Deschenes, R.J. (2007) Palmitoylation: Polic-ing Protein Stability and Traffic. Nature Reviews Molecular Cell Biology, 8, 74-84. https://doi.org/10.1038/nrm2084 |
| [24] | Morris, G., Walder, K., Puri, B.K., et al. (2016) The Deleterious Effects of Oxidative and Nitrosative Stress on Palmitoylation, Membrane Lipid Rafts and Lipid-Based Cellular Signalling: New Drug Targets in Neuroimmune Disorders. Molecular Neurobiology, 53, 4638-4658. https://doi.org/10.1007/s12035-015-9392-y |
| [25] | Blanc, M., David, F.P. and Van Der Goot, F.G. (2019) Swis-sPalm 2: Protein S-palmitoylation Database. In: Linder, M., Eds., Protein Lipidation, Vol. 2009, Humana, New York, NY, 203-214. https://doi.org/10.1007/978-1-4939-9532-5_16 |
| [26] | Cassinelli, S., Vi？ola Renart, C., Benavente Garcia, A., et al. (2022) Palmitoylation of Voltage-Gated Ion Channels. International Journal of Molecular Sciences, 23, Article 9357. https://doi.org/10.3390/ijms23169357 |
| [27] | Ko, P.J. and Dixon, S.J. (2018) Protein Palmitoylation and Cancer. EMBO Reports, 19, e46666.
https://doi.org/10.15252/embr.201846666 |
| [28] | Zhang, M.M., Zhou, L.X., Xu, Y.J., et al. (2020) A STAT3 Pal-mitoylation Cycle Promotes TH17 Differentiation and Colitis. Nature, 586, 434-439. https://doi.org/10.1038/s41586-020-2799-2 |
| [29] | Fan, Y., Shayahati, B., Tewari, R., et al. (2020) Regulation of T Cell Receptor Signaling by Protein Acyltransferase DHHC21. Molecular Biology Reports, 47, 6471-6478. https://doi.org/10.1007/s11033-020-05691-1 |
| [30] | Shayahati, B., Fan, Y., West, S., et al. (2020) Calci-um-Dependent Protein Acyltransferase DHHC21 Controls Activation of CD4+ T Cells. bioRxiv, 135, jcs258186. https://doi.org/10.1101/2020.09.01.277947 |
| [31] | Tewari, R., Shayahati, B., Fan, Y., et al. (2021) T Cell Recep-tor-Dependent S-acylation of ZAP-70 Controls Activation of T Cells. Journal of Biological Chemistry, 296, Article ID: 100311. https://doi.org/10.1016/j.jbc.2021.100311 |
| [32] | Fukata, M., Fukata, Y., Adesnik, H., et al. (2004) Identifi-cation of PSD-95 Palmitoylating Enzymes. Neuron, 44, 987-996. https://doi.org/10.1016/j.neuron.2004.12.005 |
| [33] | Jin, J.Y., Zhi, X.L., Wang, X.H., et al. (2021) Protein Pal-mitoylation and Its Pathophysiological Relevance. Journal of Cellular Physiology, 236, 3220-3233. https://doi.org/10.1002/jcp.30122 |
| [34] | Ladygina, N., Martin, B.R. and Altman, A. (2011) Dynamic Palmitoylation and the Role of DHHC Proteins in T Cell Activation and Anergy. Advances in immunology, 109, 1-44. https://doi.org/10.1016/B978-0-12-387664-5.00001-7 |
| [35] | Rana, M.S., Kumar, P., Lee, C.J., et al. (2018) Fatty Acyl Recognition and Transfer by an Integral Membrane S-Acyltransferase. Science, 359, eaao6326. https://doi.org/10.1126/science.aao6326 |
| [36] | González Montoro, A., Quiroga, R. and Valdez Taubas, J. (2013) Zinc Co-Ordination by the DHHC Cysteine-Rich Domain of the Palmitoyltransferase Swf1. Biochemical Journal, 454, 427-435. https://doi.org/10.1042/BJ20121693 |
| [37] | Malgapo, M.I.P. and Linder, M.E. (2021) Substrate Recruit-ment by zDHHC Protein Acyltransferases. Open Biology, 11, Article ID: 210026. https://doi.org/10.1098/rsob.210026 |
| [38] | Stix, R., Lee, C.J., Faraldo Gómez, J.D., et al. (2020) Structure and Mechanism of DHHC Protein Acyltransferases. Journal of Molecular Biology, 432, 4983-4998. https://doi.org/10.1016/j.jmb.2020.05.023 |
| [39] | Thomas, G.M., Hayashi, T., Chiu, S.L., et al. (2012) Palmitoylation by DHHC5/8 Targets GRIP1 to Dendritic Endosomes to Regulate AMPA-R Trafficking. Neuron, 73, 482-496. https://doi.org/10.1016/j.neuron.2011.11.021 |
| [40] | Ohno, Y., Kihara, A., Sano, T., et al. (2006) Intracellular Local-ization and Tissue-Specific Distribution of Human and Yeast DHHC Cysteine-Rich Domain-Containing Proteins. Bio-chimica et Biophysica Acta (BBA)—Molecular and Cell Biology of Lipids, 1761, 474-483. https://doi.org/10.1016/j.bbalip.2006.03.010 |
| [41] | De, I. and Sadhukhan, S. (2018) Emerging Roles of DHHC-Mediated Protein S-Palmitoylation in Physiological and Pathophysiological Context. European Journal of Cell Biology, 97, 319-338.
https://doi.org/10.1016/j.ejcb.2018.03.005 |
| [42] | Wang, J., Hao, J.W., Wang, X., et al. (2019) DHHC4 and DHHC5 Facilitate Fatty Acid Uptake by Palmitoylating and Targeting CD36 to the Plasma Membrane. Cell Reports, 26, 209-221. https://doi.org/10.1016/j.celrep.2018.12.022 |
| [43] | Cho, E. and Park, M. (2016) Palmitoylation in Alzheimer’s Dis-ease and Other Neurodegenerative Diseases. Pharmacological Research, 111, 133-151. https://doi.org/10.1016/j.phrs.2016.06.008 |
| [44] | Raymond, F.L., Tarpey, P.S., Edkins, S., et al. (2007) Mutations in ZDHHC9, Which Encodes a Palmitoyltransferase of NRAS and HRAS, Cause X-Linked Mental Retardation Associated with a Marfanoid habitus. The American Journal of Human Genetics, 80, 982-987. https://doi.org/10.1086/513609 |
| [45] | Runkle, K.B., Kharbanda, A., Stypulkowski, E., et al. (2016) Inhibition of DHHC20-Mediated EGFR Palmitoylation Creates a Dependence on EGFR Signaling. Molecular Cell, 62, 385-396. https://doi.org/10.1016/j.molcel.2016.04.003 |
| [46] | Chen, X.R., Hu, L., Yang, H.R., et al. (2019) DHHC Protein Family Targets Different Subsets of Glioma Stem Cells in Specific Niches. Journal of Experimental & Clinical Cancer Research, 38, Article No. 25.
https://doi.org/10.1186/s13046-019-1033-2 |
| [47] | Guo, H.L., Wang, J., Ren, S., et al. (2022) Targeting EGFR-Dependent Tumors by Disrupting an ARF6-Mediated Sorting System. Nature Communications, 13, Article No. 6004. https://doi.org/10.1038/s41467-022-33788-7 |
| [48] | Jennings, B.C. and Linder, M.E. (2012) DHHC Protein S-Acyltransferases Use Similar Ping-Pong Kinetic Mechanisms but Display Different Acyl-CoA Specificities. Journal of Biological Chemistry, 287, 7236-7245.
https://doi.org/10.1074/jbc.M111.337246 |
| [49] | Mitchell, D.A., Mitchell, G., Ling, Y.P., et al. (2010) Mutational Analysis of Saccharomyces cerevisiae Erf2 Reveals a Two-Step Reaction Mechanism for Protein Palmitoylation by DHHC Enzymes. Journal of Biological Chemistry, 285, 38104-38114. https://doi.org/10.1074/jbc.M110.169102 |
| [50] | Gottlieb, C.D. and Linder, M.E. (2017) Structure and Function of DHHC Protein S-acyltransferases. Biochemical Society Transactions, 45, 923-928. https://doi.org/10.1042/BST20160304 |
| [51] | Montoro, A.G., Ramirez, S.C. and Taubas, J.V. (2015) The Canonical DHHC Motif Is Not Absolutely Required for the Activity of the Yeast S-acyltransferases Swf1 and Pfa4. Journal of Bi-ological Chemistry, 290, 22448-22459.
https://doi.org/10.1074/jbc.M115.651356 |
| [52] | Brownlie, R.J. and Zamoyska, R. (2013) T Cell Receptor Signalling Networks: Branched, Diversified and Bounded. Nature Reviews Immunology, 13, 257-269. https://doi.org/10.1038/nri3403 |
| [53] | Gaud, G., Lesourne, R. and Love, P.E. (2018) Regulatory Mechanisms in T Cell Receptor Signalling. Nature Reviews Immunology, 18, 485-497. https://doi.org/10.1038/s41577-018-0020-8 |
| [54] | Hwang, J.R., Byeon, Y., Kim, D., et al. (2020) Recent Insights of T Cell Receptor-Mediated Signaling Pathways for T Cell Activation and Development. Experimental & Molecular Medi-cine, 52, 750-761.
https://doi.org/10.1038/s12276-020-0435-8 |
| [55] | Zhang, Y.Q., Qin, Z.R., Sun, W.H., et al. (2021) Function of Protein S-palmitoylation in Immunity and Immune-Related Diseases. Frontiers in Immunology, 12, Article 661202. https://doi.org/10.3389/fimmu.2021.661202 |
