Review
Immunology
Charneal L. Dixon, Katrina Mekhail, Gregory D. Fairn
Summary: Phagocytosis is a process used by cells to engulf particles, with proteins modified by lipids to regulate signal transduction and immune functions. S-acylation, specifically S-palmitoylation, is a reversible modification that plays a role in regulating phagocytosis and phagosome biology in macrophages.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Cell Biology
Muhammad U. Anwar, F. Gisou van der Goot
Summary: S-acylation is an important posttranslational modification that regulates cellular processes. This reversible lipid modification affects cellular pathways and physiological processes, and the enzymes and proteins involved in S-acylation are still being discovered and studied.
JOURNAL OF CELL BIOLOGY
(2023)
Article
Neurosciences
Fanny L. Lemarie, Nicholas S. Caron, Shaun S. Sanders, Mandi E. Schmidt, Yen T. N. Nguyen, Seunghyun Ko, Xiaohong Xu, Mahmoud A. Pouladi, Dale D. O. Martin, Michael R. Hayden
Summary: Research has shown that palmitoylation of mHTT and HIP14/HIP14L substrates is decreased early in Huntington's disease models, further decreasing with aging. Palmitoylation of mHTT can be normalized using an APT inhibitor, reducing mHTT aggregation and cytotoxicity.
NEUROBIOLOGY OF DISEASE
(2021)
Review
Biochemistry & Molecular Biology
Alice Main, William Fuller
Summary: This review discusses the role of lipid post-translational modification S-palmitoylation in diseases and the advancements in experimental tools in the field. Understanding how palmitoylation controls protein localization and function may lead to its modulation as a therapeutic strategy in the future.
Review
Cell Biology
Jiayu Jin, Xiuling Zhi, Xinhong Wang, Dan Meng
Summary: Protein palmitoylation, a common lipid modification, plays important roles in regulating protein stability and cellular processes by attaching fatty acid chains to cysteine residues. The reversibility of palmitoylation allows proteins to shuttle rapidly between membranes and the cytoplasm, with mutations in PATs being closely linked to various human diseases.
JOURNAL OF CELLULAR PHYSIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Valentina Buffa, Giorgia Adamo, Sabrina Picciotto, Antonella Bongiovanni, Daniele P. Romancino
Summary: Protein S-palmitoylation is a reversible lipid modification involving the addition of palmitic acid to cysteine residues. It plays various roles in cellular processes and is associated with diseases. This study presents an optimized method using Acyl Biotin Exchange (ABE) chemistry to detect protein palmitoylation. The resulting protocol is more sensitive and reproducible than the conventional approach.
Review
Physiology
Savannah J. West, Darren Boehning, Askar M. Akimzhanov
Summary: S-acylation is a reversible lipidation process that plays a crucial role in regulating T cell function by controlling protein localization, stability, and interactions.
FRONTIERS IN PHYSIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Saara-Anne Azizi, Tong Lan, Clemence Delalande, Rahul S. Kathayat, Fernando Banales Mejia, Alice Qin, Noah Brookes, Perla Jasmine Sandoval, Bryan C. Dickinson
Summary: Protein S-acylation is a dynamic lipid post-translational modification that can modulate the localization and activity of target proteins. A new broad-spectrum DHHC family inhibitor called cyano-myracrylamide (CMA) was synthesized and characterized, showing potent inhibition of DHHC family proteins with decreased toxicity and avoidance of inhibiting the S-acylation eraser enzymes. CMA provides an improved chemical scaffold for understanding the complexities of DHHC-mediated cell signaling by protein S-acylation.
ACS CHEMICAL BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Elena Porcellato, Juan Carlos Gonzalez-Sanchez, Constantin Ahlmann-Eltze, Mahmoud Ali Elsakka, Itamar Shapira, Juergen Fritsch, Juan Antonio Navarro, Simon Anders, Robert B. Russell, Felix T. Wieland, Christoph Metzendorf
Summary: Protein S-palmitoylation, a reversible protein modification, plays a crucial role in neuronal diseases and cancer. However, its study in Drosophila melanogaster has been limited. In this study, the palmitoylome of Drosophila S2R+ cells was analyzed, and a method called DHHC-BioID was established to identify client proteins and interaction partners of protein acyl-transferases (PATs). The results showed that S-palmitoylated proteins are conserved between mammals and Drosophila, and DHHC-BioID is a sensitive and specific method for identifying DHHC-PAT client proteins.
Article
Biochemistry & Molecular Biology
Yingmin Sun, Keyong Du
Summary: The association of AMP-activated protein kinase (AMPK) with membranes is crucial for its activation and function. Protein lipid modification, such as palmitoylation, myristoylation, and farnesylation, plays an important role in regulating protein-membrane interactions. This study focuses on the palmitoylation of AMPK alpha, which is essential for its activation and subcellular compartmentalization. The researchers identified DHHC17 as a candidate palmitoyltransferase for AMPK alpha and found that DHHC17 modulates AMPK membrane association and activation. Knocking out DHHC17 in the liver impaired AMPK activation and hepatic autophagy, leading to a diabetes-like syndrome. These findings highlight the critical role of AMPK alpha palmitoylation in its activation and DHHC17 as a novel regulator of hepatic metabolism.
MOLECULAR AND CELLULAR BIOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Minxuan Xu, Jun Tan, Liancai Zhu, Chenxu Ge, Yi Zhang, Fufeng Gao, Xianling Dai, Qin Kuang, Jie Chai, Benkui Zou, Bochu Wang
Summary: Underestimation of the complexity of NASH pathogenesis hinders the development of new drugs and targeted therapies. This study revealed that IRHOM2 is post-translationally S-palmitoylated at C476, which facilitates its translocation and stabilization. ZDHHC3 was identified as the key acetyltransferase required for IRHOM2 palmitoylation, and its increased association with IRHOM2 promotes palmitoylation and prevents ubiquitination-mediated degradation.
Review
Immunology
Yuqi Zhang, Ziran Qin, Wenhuan Sun, Feng Chu, Fangfang Zhou
Summary: Protein S-palmitoylation is a crucial lipid modification that regulates protein function in various biological processes. Recent studies have shown that palmitoylation plays significant roles in immune function by targeting immune-related proteins to the cellular membrane and lipid rafts. Aberrant protein acylation and changes in palmitoylation levels are linked to human immunologic diseases, making targeting palmitoylation a novel therapeutic approach for treating such disorders.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Jessica J. Chen, Ying Fan, Darren Boehning
Summary: Protein S-acylation is a reversible process of adding fatty acids to cysteine residues of target proteins, which plays crucial roles in regulating protein function. Enzymes known as palmitoyl acyltransferases, with conserved DHHC amino acid sequence at their active site, regulate this process with varied substrate selection, preference, and mechanisms. S-acylation is now understood to be dynamic and important in signaling transduction in various cell types.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2021)
Article
Microbiology
Dina A. Abdulrahman, Xiaorong Meng, Michael Veit
Summary: Recent pandemics caused by zoonotic coronaviruses and influenza A viruses have shown that viral glycoproteins and ion channels are S-acylated. DHHC family members play a crucial role in palmitoylation, with a common set of DHHCs acylating SARS-CoV-2 and Flu A proteins in human cells. This highlights the potential of DHHCs as targets for broad-spectrum antiviral drugs.
Article
Biochemistry & Molecular Biology
Wei Yu, Kan Yang, Mengmiao Zhao, Han Liu, Zhihao You, Zhenming Liu, Xiaoqiang Qiao, Yali Song
Summary: A series of novel covalent S-acylation inhibitors were designed through synthesis, and most of them exhibited better anti-proliferation effects on MCF-7, MGC-803, and U937 cell lines compared to 2-BP. Compound 8d, 8i, 8j, and 10e showed significant inhibitory effects on MCF-7 cells, with -IC50 values below 20 μM. Furthermore, these inhibitors had less toxic effects on 3T3 cell line than 2-BP. Inhibition of S-acylation was observed for most of the compounds, with 8i showing the highest inhibitory rate of 89.3% at a concentration of 20 μM. Molecular docking revealed the conjugation of 8i with surrounding amino acids. Additionally, 8i not only suppressed the migration of MCF-7 cells but also induced cell apoptosis by arresting them in the G0/G1 phase.
MOLECULAR DIVERSITY
(2023)
Article
Chemistry, Physical
Elisa Herrera, Javier Valdez Taubas, Carla E. Giacomelli
APPLIED SURFACE SCIENCE
(2015)
Article
Biochemistry & Molecular Biology
Ayelen Gonzalez Montoro, Sabrina Chumpen Ramirez, Javier Valdez Taubas
JOURNAL OF BIOLOGICAL CHEMISTRY
(2015)
Article
Biochemistry & Molecular Biology
Constanza Feliziani, Javier Valdez Taubas, Sofia Moyano, Gonzalo Quassollo, Joanna E. Poprawski, Beverly Wendland, Maria C. Touz
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
(2016)
Article
Cell Biology
Ayelen Gonzalez Montoro, Gonzalo Bigliani, Javier Valdez Taubas
JOURNAL OF CELL SCIENCE
(2017)
Article
Genetics & Heredity
Carlos Anton, Javier Valdez Taubas, Cesar Roncero
Article
Genetics & Heredity
Carlos Anton, Javier Valdez Taubas, Cesar Roncero
Article
Biochemistry & Molecular Biology
Ayelen Gonzalez Montoro, Rodrigo Quiroga, Hugo J. F. Maccioni, Javier Valdez Taubas
BIOCHEMICAL JOURNAL
(2009)
Article
Biochemistry & Molecular Biology
Ayelen Gonzalez Montoro, Rodrigo Quiroga, Javier Valdez Taubas
BIOCHEMICAL JOURNAL
(2013)
Article
Cell Biology
Rodrigo Quiroga, Alejandra Trenchi, Ayelen Gonzalez Montoro, Javier Valdez Taubas, Hugo J. F. Maccioni
JOURNAL OF CELL SCIENCE
(2013)
Article
Multidisciplinary Sciences
Ayelen Gonzalez Montoro, Sabrina Chumpen Ramirez, Rodrigo Quiroga, Javier Valdez Taubas
Article
Biochemistry & Molecular Biology
Consuelo Coronel Arrechea, Maria Luz Giolito, Iris Alejandra Garcia, Gaston Soria, Javier Valdez Taubas
Summary: Protein palmitoylation, a common post-translational modification, plays important roles in various cancers, neurodegenerative diseases, and infectious diseases. Lack of specific inhibitors has hampered research progress in this field. A yeast-based high-throughput method has been developed to screen for small molecules that inhibit protein palmitoylation effectively.
Article
Biochemistry & Molecular Biology
Sabrina Chumpen Ramirez, Fernando M. Ruggiero, Jose Luis Daniotti, Javier Valdez Taubas
BIOCHEMICAL JOURNAL
(2017)
Article
Biochemistry & Molecular Biology
Michala Eichner Techau, Javier Valdez-Taubas, Jean-Francois Popoff, Richard Francis, Matthew Seaman, Jenefer M. Blackwell
JOURNAL OF BIOLOGICAL CHEMISTRY
(2007)
Article
Biochemistry & Molecular Biology
J Valdez-Taubas, H Pelham