Review
Biochemistry & Molecular Biology
Yanxiang Meng, Jarrod J. Sandow, Peter E. Czabotar, James M. Murphy
Summary: This article discusses the role of phosphorylation, ubiquitylation, GlcNAcylation, proteolytic cleavage, and disulfide bonding in regulating necroptotic signaling, with a focus on RIPK1, RIPK3, and MLKL. Understanding of these post-translational modifications can be valuable in efforts to therapeutically modulate necroptosis.
CELL DEATH AND DIFFERENTIATION
(2021)
Article
Biochemistry & Molecular Biology
Antonieta L. Salguero, Maggie Chen, Aaron T. Balana, Nam Chu, Hanjie Jiang, Brad A. Palanski, Hwan Bae, Katharine M. Wright, Sara Nathan, Heng Zhu, Sandra B. Gabelli, Matthew R. Pratt, Philip A. Cole
Summary: This study investigates the regulatory effects of phosphorylation of Tyr474 and O-GlcNAcylation of Ser473 on Akt, finding that both modifications can increase Akt's kinase activity toward substrates. Kinase assays using protein microarrays showed high similarity in the protein substrates phosphorylated by phosphoSer473 Akt and O-GlcNAcSer473 Akt. Two Akt substrates, PPM1H and NEDD4L, were validated in further solution-phase assays and cell transfection experiments.
ACS CHEMICAL BIOLOGY
(2022)
Review
Oncology
Ana Gonzalez-Garcia, Antonio Garrido, Ana C. Carrera
Summary: Genetic alterations in the PI3-kinase/PTEN pathway are common in cancer cells. Current efforts to treat PTEN-dependent tumors mainly focus on PI3-kinase inhibition, but modulating PTEN post-translational modifications could provide alternative therapeutic strategies.
Review
Biochemistry & Molecular Biology
Jia Yu, David M. Virshup
Summary: Wnts are lipid-modified signaling glycoproteins that play critical roles in development and homeostasis. Their function is regulated by post-translational modifications, such as O-linked palmitoleation. The abundance and activity of Wnt are controlled by intracellular recycling, ubiquitylation-mediated degradation, and cleavage by metalloprotease TIKI. Understanding these modifications provides insights into the regulation of Wnt signaling.
BIOCHEMICAL SOCIETY TRANSACTIONS
(2022)
Review
Cell Biology
Chunhua Yang, Mengna Wei, Yanpu Zhao, Zhanyi Yang, Mengyao Song, Jia Mi, Xiaoyong Yang, Geng Tian
Summary: Post-translational modifications (PTMs) in pancreatic beta cells play crucial roles in insulin secretion and have significant implications for diabetes mellitus development. This article summarizes the major PTMs occurring in beta cells and their impact on insulin secretion, providing valuable insights into the understanding of insulin secretion mechanisms and potential therapeutic targets for diabetes from the perspective of protein PTMs.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Pharmacology & Pharmacy
Juan Facundo Chrestia, Ornella Turani, Noelia Rodriguez Araujo, Guillermina Hernando, Maria del Carmen Esandi, Cecilia Bouzat
Summary: Nicotinic acetylcholine receptors (nAChRs) are widely distributed in the central and peripheral nervous system and play crucial roles in vital physiological processes. Post-translational modifications (PTMs) have been shown to regulate different aspects of nAChR life cycle, but our knowledge in this field is still limited and many important aspects remain unknown.
PHARMACOLOGICAL RESEARCH
(2023)
Article
Plant Sciences
Manuel Balparda, Maroua Bouzid, Maria del Pilar Martinez, Ke Zheng, Markus Schwarzlaender, Veronica G. Maurino
Summary: The flexibility of plant growth, development and stress responses is controlled by signaling cascades and genetic programs, while metabolism executes these programs through selective delivery of building blocks and energy. Photosynthetic carbon fixation is essential for plant metabolism, which is influenced by environmental fluctuations. The regulation of carbon assimilation metabolism requires versatility and rapidity to maintain efficiency. Post-translational modifications (PTMs) have a significant impact on carbon assimilation metabolism, altering protein characteristics and function. The exploitation of PTMs has the potential to control metabolic flux, influence crop yields, modify metabolite composition, optimize stress tolerance, and regulate growth and developmental programs.
Review
Cell Biology
Clotilde C. N. Renaud, Nicolas Bidere
Summary: Centriolar satellites are small granules that revolve around the centrosome, and recent research has uncovered their complex nature and diverse roles in cellular processes beyond centrosome and primary cilia formation. Post-translational modifications like phosphorylation and ubiquitination play a crucial role in shaping the composition and functions of these structures.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Virology
Celia Chamontin, Guillaume Bossis, Sebastien Nisole, Nathalie J. Arhel, Ghizlane Maarifi
Summary: Intrinsic immunity is mediated by host cellular proteins called restriction factors which interfere with viral replication and are tightly regulated by interferons. Post-translational modifications play a crucial role in determining the antiviral activity of restriction factors, with viruses evolving mechanisms to counteract these modifications. Understanding the role of PTMs in restriction factors is essential for comprehending antiviral defense mechanisms and immune response regulations during infection.
Review
Biochemistry & Molecular Biology
Qiuchen Qi, Suli Yang, Juan Li, Peilong Li, Lutao Du
Summary: Aberrant redox homeostasis, characterized by enhanced intracellular reactive oxygen species (ROS) and antioxidant defenses, is a well-known cancer hallmark. Epigenetic modifications and post-translational modifications (PTMs), such as DNA/RNA methylation, can modulate redox homeostasis and participate in tumor progression.
ANTIOXIDANTS & REDOX SIGNALING
(2023)
Review
Cell Biology
Na Yeon Park, Doo Sin Jo, Dong-Hyung Cho
Summary: Autophagy is a crucial cellular process involved in stress response and the elimination of cellular components. ATG4, the sole cysteine protease, regulates autophagy by promoting autophagosome maturation through reversible lipidation and delipidation of ATG8 homologs. Post-translational modifications of ATG4 play a role in modulating its activity and autophagy.
Article
Biochemistry & Molecular Biology
Yifat Geffen, Shankara Anand, Yo Akiyama, Tomer M. Yaron, Yizhe Song, Jared L. Johnson, Akshay Govindan, Ozgun Babur, Yize Li, Emily Huntsman, Liang-Bo Wang, Chet Birger, David I. Heiman, Qing Zhang, Mendy Miller, Yosef E. Maruvka, Nicholas J. Haradhvala, Anna Calinawan, Saveliy Belkin, Alexander Kerelsky, Karl R. Clauser, Karsten Krug, Shankha Satpathy, Samuel H. Payne, D. R. Mani, Michael A. Gillette, Saravana M. Dhanasekaran, Mathangi Thiagarajan, Mehdi Mesri, Henry Rodriguez, Ana I. Robles, Steven A. Carr, Alexander J. Lazar, Francois Aguet, Lewis C. Cantley, Li Ding, Gad Getz
Summary: This study analyzed PTM data from 1,110 patients across 11 cancer types and revealed patterns of protein acetylation and phosphorylation changes related to cancer processes. The study identified subsets of tumors from different cancer types and highlighted potential therapeutic targets.
Review
Biochemistry & Molecular Biology
Bo Dong, Yadi Wu
Summary: SNAI1, a zinc finger transcription factor, plays a crucial role in cancer metastasis by regulating transcriptional, translational, and post-translational levels. Epigenetic regulation and post-translational modifications are key mechanisms for the regulation of SNAI1 in cancer metastasis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Oncology
Le Yu, Ian J. Davis, Pengda Liu
Summary: Ewing sarcoma is a malignant pediatric bone cancer characterized by unique gene fusions, with EWSR1-FLI1 being the most prevalent. The understanding of regulatory mechanisms and potential therapeutic approaches for targeting EWSR1-FLI1 in Ewing sarcoma is still insufficient. This review provides a summary of up-to-date knowledge on the subject, aiming to identify knowledge gaps and propose new therapeutic directions.
Review
Biotechnology & Applied Microbiology
Haiying Wang, Liqian Yang, Minghui Liu, Jianyuan Luo
Summary: Posttranslational modifications (PTMs) of proteins play important roles in regulating cellular physiological and pathological processes. New modifications like succinylation, hydroxybutyrylation, and lactylation introduce a new layer to protein regulation with wide application prospects.
CANCER GENE THERAPY
(2023)
Article
Hematology
Xin Li, Zi Sheng, Yuanxin Sun, Yuanjian Wang, Miao Xu, Zhiyue Zhang, Hui Li, Linlin Shao, Yanqi Zhang, Jinming Yu, Chunhong Ma, Chengjiang Gao, Ming Hou, Heyu Ni, Jun Peng, Ji Ma, Qi Feng
Summary: The expression of HLA-G and immunoglobulin-like transcripts is found to be impaired in patients with ITP. Recombinant HLA-G can correct this abnormality by upregulating immunoglobulin-like transcripts, stimulating Th2 differentiation, and downregulating Th1 and Th17 immune responses, suggesting that HLA-G can be a potential diagnostic marker and therapeutic option for ITP.
Article
Immunology
Yunyun Guo, Fei Jiang, Lingli Kong, Haifeng Wu, Honghai Zhang, Xiaorong Chen, Jian Zhao, Baoshan Cai, Yanqi Li, Chunhong Ma, Fan Yi, Lei Zhang, Bingyu Liu, Yi Zheng, Lingqiang Zhang, Chengjiang Gao
Summary: STING is a critical adaptor protein for innate antiviral and antitumor immunity, regulated by protein ubiquitination, with OTUD5 identified as a key deubiquitinase that interacts with STING to maintain its stability. Knockout of OTUD5 resulted in impaired immune responses and increased susceptibility to viral infection and tumor development.
CELLULAR & MOLECULAR IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Jian Cui, Na Zhang, Ying Liu, Lei Zhang, Chengjiang Gao, Suxia Liu
Summary: TIPE2 regulates apoptosis of HBV-infected hepatocytes by upregulating expression of pro-apoptotic genes, leading to increased cell death in virus-infected cells.
MOLECULAR IMMUNOLOGY
(2021)
Review
Microbiology
Fanhua Wei, Chengjiang Gao, Yujiong Wang
Summary: Influenza virus infection can lead to cytokine storms, contributing to severe outcomes. Immunomodulatory drugs offer a promising approach for treating hypercytokinemia induced by acute viral infections.
CRITICAL REVIEWS IN MICROBIOLOGY
(2022)
Article
Immunology
Chao Sui, Tongyang Xiao, Shengyuan Zhang, Hongxiang Zeng, Yi Zheng, Bingyu Liu, Gang Xu, Chengjiang Gao, Zheng Zhang
Summary: This study reveals that SARS-CoV-2 inhibits the host interferon response by using NSP13 to recruit TBK1 for autophagic degradation. The findings provide new insights into the transmission and pathogenesis of SARS-CoV-2 infection.
JOURNAL OF IMMUNOLOGY
(2022)
Article
Virology
Lulu Han, Yi Zheng, Jian Deng, Mei-Ling Nan, Yang Xiao, Meng-Wei Zhuang, Jing Zhang, Wei Wang, Chengjiang Gao, Pei-Hui Wang
Summary: A characteristic feature of COVID-19 is the dysregulated immune response and overwhelming inflammatory cytokine storm. This study demonstrates that the ORF10 protein of SARS-CoV-2 interacts with STING, impairing the cGAS-STING signaling pathway and weakening the innate antiviral immunity.
JOURNAL OF MEDICAL VIROLOGY
(2022)
Article
Multidisciplinary Sciences
Xuemei Bai, Chao Sui, Feng Liu, Tian Chen, Lei Zhang, Yi Zheng, Bingyu Liu, Chengjiang Gao
Summary: This study discovered that PRMT9 directly targets MAVS and methylates it, inhibiting the aggregation and autoactivation of MAVS. This provides an explanation for the regulatory mechanism of MAVS in maintaining innate immune homeostasis.
NATURE COMMUNICATIONS
(2022)
Article
Virology
Jian Deng, Sheng-Nan Zheng, Yang Xiao, Mei-Ling Nan, Jing Zhang, Lulu Han, Yi Zheng, Yanying Yu, Qiang Ding, Chengjiang Gao, Pei-Hui Wang
Summary: SARS-CoV-2 NSP8 inhibits the production of type I and III interferons by targeting RIG-I/MDA5, TRIF, and STING signaling molecules. It disrupts the assembly of RIG-I/MDA5-MAVS complex, resulting in impaired phosphorylation and nuclear translocation of IRF3. NSP8 also directly interacts with TRIF and STING to suppress their signaling transduction.
JOURNAL OF MEDICAL VIROLOGY
(2023)
Article
Virology
Jian Deng, Yi Zheng, Sheng-Nan Zheng, Mei-Ling Nan, Lulu Han, Jing Zhang, Yunyun Jin, Ji-An Pan, Chengjiang Gao, Pei-Hui Wang
Summary: The NSP7 protein of SARS-CoV-2 inhibits the production of interferons, crucial components of antiviral immunity, by targeting multiple signaling pathways. It disrupts the normal functioning of RIG-I/MDA5, TLR3-TRIF, and cGAS-STING pathways, leading to a dampened interferon response. Additionally, NSP7 decreases immune activation and facilitates virus replication.
JOURNAL OF MEDICAL VIROLOGY
(2023)
Article
Multidisciplinary Sciences
Mutian Jia, Yuanyuan Wang, Jie Wang, Danhui Qin, Mengge Wang, Li Chai, Yue Fu, Chunyuan Zhao, Chengjiang Gao, Jihui Jia, Wei Zhao
Summary: This study demonstrates that STING-triggered autophagy plays a crucial role in eliminating pathogens and limiting STING-induced interferon responses. Specifically, myristic acid attenuates IFN responses while enhancing STING-dependent autophagy, contributing to immune homeostasis. Mechanistically, myristic acid promotes N-myristoylation of ARF1, which controls STING membrane trafficking and enhances autophagy degradation of the STING complex. Targeting myristic acid and N-myristoylation could be a promising approach for treating diseases caused by aberrant STING activation.
NATURE COMMUNICATIONS
(2023)
Article
Cell Biology
Lingli Kong, Chao Sui, Tian Chen, Lei Zhang, Wei Zhao, Yi Zheng, Bingyu Liu, Xiaochen Cheng, Chengjiang Gao
Summary: Researchers have identified TRIM10 as a positive regulator of STING signaling, showing that it enhances the STING-dependent type I interferon response by promoting STING aggregation and interaction with TBK1. TRIM10-deficient cells and mice are more susceptible to viral infections and exhibit faster melanoma growth.
Article
Immunology
Feng Liu, Wanxin Zhuang, Bin Song, Yuan Yang, Junqi Liu, Yi Zheng, Bingyu Liu, Jie Zheng, Wei Zhao, Chengjiang Gao
Summary: In this study, the researchers discovered that K63-linked polyubiquitin chains loaded on MAVS can be recognized by RIG-I to initiate MAVS aggregation. They also identified Ube2N as a major enzyme involved in the polyubiquitination of MAVS and found that it cooperates with Riplet and TRIM31 to promote unanchored polyubiquitination. Additionally, they identified USP10 as a deubiquitinating enzyme that removes unanchored polyubiquitin chains from MAVS.
CELLULAR & MOLECULAR IMMUNOLOGY
(2023)
Article
Immunology
Yi Zheng, Xuejing Zhang, Chengjiang Gao
CELLULAR & MOLECULAR IMMUNOLOGY
(2023)
Article
Immunology
Wanxin Zhuang, Lei Zhang, Yi Zheng, Bingyu Liu, Chunhong Ma, Wei Zhao, Suxia Liu, Feng Liu, Chengjiang Gao
Summary: Inflammasomes are crucial for the innate immune system, and dysregulation of their activation can have negative impacts on human health. This study reveals that USP3 acts as a key regulator of ASC ubiquitination, enhancing its stability and promoting inflammasome activation.
CELLULAR & MOLECULAR IMMUNOLOGY
(2022)
Article
Biochemical Research Methods
Zhenzhen Yan, Hansen Liu, Chengjiang Gao
Summary: This article presents a protocol for detecting the aggregation of TBK1 upon viral infection using HSV-1 infected mouse peritoneal macrophages, which can be adapted for other proteins and viruses.
