Article
Virology
Lei Hou, Xiaohan Hu, Jinshuo Guo, Rong Quan, Li Wei, Jing Wang, Jiangwei Song, Jue Liu
Summary: In this study, we found that aMPV/C infection induces MAVS degradation through the ubiquitin-proteasome pathway at the post-translational level. Furthermore, specific amino acid sites were identified as pivotal in the formation of polyubiquitin chains during MAVS degradation. E3 ubiquitin ligases targeting MAVS were also identified, with RNF5 shown to be involved in MAVS degradation in aMPV/C-infected cells.
Article
Genetics & Heredity
Hongbiao Ran, Chunyan Li, Ming Zhang, Jincheng Zhong, Hui Wang
Summary: Ubiquitination, a post-transcriptional modification, plays a crucial role in protein degradation and is involved in various physiological and pathological processes, including animal adipogenesis. The E3 ligases have been found to regulate adipogenesis, but their role in the recognition and connection between substrate and ubiquitin during ubiquitination has been overlooked. This review summarizes the regulatory and modification targets of E3 ligases in animal adipogenesis, explains the regulatory mechanisms in lipogenic pathways, and analyzes existing positive results, providing valuable research directions for further understanding the regulatory mechanisms of E3 ligases in animal adipogenesis.
Article
Biochemistry & Molecular Biology
Seung-Heon Baek, Yeun-Kyu Jang
Summary: AMBRA1 negatively regulates ALDH1B1 through noncanonical ubiquitination, mediated by cooperation with E3 ligases like TRAF6. It controls the K27- and K33-linked ubiquitination of ALDH1B1, impacting its expression and self-association ability.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Debdeep Dutta, Vartika Sharma, Mousumi Mutsuddi, Ashim Mukherjee
Summary: Notch signaling is an evolutionarily conserved pathway widely used for multiple cellular events during development. The pathway is tightly regulated by physical and biochemical modifications of the Notch receptor and its ligand, as well as through the process of ubiquitination carried out by E3 ubiquitin ligases to maintain proper signaling outcomes. Dysregulation of ubiquitination in Notch signaling can lead to abnormal signaling and contribute to various human diseases.
Article
Microbiology
Xing Yang, Zhijuan Hu, Jingjie Yuan, Run Zou, Yilan Wang, Xuan Peng, Shan Xu, Chengjian Xie
Summary: Two ubiquitin ligase E3 genes (VdBre1 and VdHrd1) in Verticillium dahliae are intrinsically associated with virulence, and their deletion significantly impairs the ability of the fungus to colonize plants and form penetration pegs. VdBre1 governs the lipid metabolism pathway, while VdHrd1 participates in endoplasmic-reticulum-related processes. The Delta VdBre1 mutant shows a significant decrease in histone ubiquitination and histone H3K4 trimethylation levels.
Review
Cell Biology
Kan Lu, Yonglong Pan, Zhao Huang, Huifang Liang, Ze-Yang Ding, Bixiang Zhang
Summary: The TRIM protein family is a versatile and highly conserved group of proteins that function as E3 ligases, regulating the development of hepatocellular carcinoma.
JOURNAL OF BIOMEDICAL SCIENCE
(2022)
Article
Biology
Lu Zhu, Qing Zhang, Ciro D. Cordeiro, Sudeep Banjade, Richa Sardana, Yuxin Mao, Scott D. Emr
Summary: The study reveals a novel ubiquitination modification implemented by Rsp5 adaptor proteins, which controls the recruitment and activity of Rsp5 to facilitate the turnover of membrane proteins.
Article
Virology
Fernando Villalon-Letelier, Rubaiyea Farrukee, Sarah L. Londrigan, Andrew G. Brooks, Patrick C. Reading
Summary: MARCH1 isoforms have differential abilities to restrict influenza A virus (IAV) infectivity. While MARCH1.2 lacks the ability to restrict IAV infectivity, the deletion of its N-terminal cytoplasmic domain (N-CT) restores the viral inhibition. Furthermore, MARCH1.2 is expressed at higher levels in unstimulated human peripheral blood mononuclear cells and monocyte-derived macrophages.
Review
Endocrinology & Metabolism
Jianrong Chen, Xianjie Feng, Xu Zhou, Yong Li
Summary: Emerging evidence suggests that ubiquitin-mediated degradation of insulin-signalling-related proteins is involved in insulin resistance and its related disorders. Tripartite motif-containing (TRIM) proteins, a superfamily of E3 ubiquitin ligases, control protein levels and function through ubiquitination, and recent research shows their importance in metabolic disorders. This review provides an overview of the latest evidence linking TRIMs to insulin resistance and its related disorders, their roles in regulating various cellular processes, and recent advances in TRIM-targeted drug development.
DIABETES OBESITY & METABOLISM
(2023)
Article
Biology
Aiqin Sun, Jun Zhu, Song Xia, Yanling Li, Tiantian Wu, Genbao Shao, Wannian Yang, Qiong Lin
Summary: The study revealed that NEDD4 interacts with MEKK5 through a conserved WW3 domain, but MEKK5 is not a ubiquitination substrate of NEDD4 and instead negatively regulates NEDD4-mediated ubiquitination. Overexpression of MEKK5 significantly reduces NEDD4-promoted lung cancer cell migration.
Review
Cell Biology
Yi Xiong, Chao Yu, Qianting Zhang
Summary: This review discusses the functions of ubiquitin proteasome system (UPS) components in mammalian spermatogenesis, including the composition of proteasome isoforms at each stage, the specificity and associated degradation events of each isoform, E3 ubiquitin ligases mediating protein ubiquitination, and the deubiquitinases involved in spermatogenesis and male fertility. Exploring the UPS machineries in spermatogenesis provides insights into protein dynamics during male germ cell production and sheds light on the etiology and pathogenesis of human male infertility.
Article
Physiology
MuChun Tsai, Rachael E. Rayner, Lexie Chafin, Daniela Farkas, Jessica Adair, Chelsea Mishan, Rama K. Mallampalli, Sun Hee Kim, Estelle Cormet-Boyaka, James D. Londino
Summary: Respiratory viruses, such as influenza, decrease airway cilia function and expression, which leads to reduced clearance of mucus and weakened immune defense. The study found that MARCH10, an E3 ligase expressed in ciliated epithelial cells, is significantly decreased during influenza infection in mice, human lung epithelial cells, and human lung tissue. Knockdown of MARCH10 resulted in reduced ciliary beat frequency and decreased levels of a ciliary component, while overexpression of MARCH10 decreased influenza hemagglutinin protein levels and modulated IL-1b cytokine expression. These findings suggest that MARCH10 may play a protective role in airway pulmonary host defense and innate immunity during influenza infection.
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
(2023)
Review
Pharmacology & Pharmacy
Sunil Singh, Joel Ng, J. Sivaraman
Summary: The HECT E3 ligase family consists of three sub-families: NEDD4, HERC, and Other, with the latter being less explored. Members of the Other subfamily have diverse N-terminal regions preceding the conserved HECT domains, which influence the stability and activity of the proteins. They assemble atypical ubiquitin linkages and cooperate with E3 ligases from other subfamilies to form branched ubiquitin chains on substrates, making them potential candidates for therapeutic drug development.
PHARMACOLOGY & THERAPEUTICS
(2021)
Review
Cell Biology
Lidong Wang, Xiaodan Sun, Jingni He, Zhen Liu
Summary: Ubiquitination is a significant posttranslational modification affecting protein stability and function, with the specificity of substrate recognition determined by ubiquitin E3 ligase. The human Deltex (DTX) protein family, functioning as E3 ligases, has five members and plays crucial roles in various physiological and pathological processes, although there is still limited understanding of their structural features and mechanisms of action despite extensive research.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Cell Biology
Manuel Olazabal-Moran, Miriam Sanchez-Ortega, Laura Martinez-Munoz, Carmen Hernandez, Manuel S. Rodriguez, Mario Mellado, Ana C. Carrera
Summary: PI3-kinase and PTEN regulate the PIP3/AKT signaling pathway through the ubiquitin ligase cCBL, influencing cell survival, division, and migration. These findings reveal a novel mechanism for PI3-kinase/PTEN crosstalk and suggest that cCBL may be a potential target for modulating PTEN activity in cancer.