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MARCH2 inhibits avian leukosis virus replication by targeting gp85 for ubiquitination and degradation.

The replication of avian leukosis virus (ALV), a simple retrovirus that induces neoplastic diseases in chickens, is regulated by host factor … to 10.70-fold. MARCH2 was found to interact with the viral gp85 protein, catalyzing its K27-linked ubiquitination and proteasomal degradation at lysine 282 (K282). Substituting K282 with arginine prevented degradation and enhanced ALV-A replication. Importantly, the K282 site was determined to be conserved across various ALV subgroups, with its mutation disrupt …

Qihuang Zhuyu formula mitigates cardiomyocyte apoptosis and hypertrophy via Bmal1-mediated P53 ubiquitination.

BACKGROUND: Cardiac remodeling, a pathological process induced by hypertension and related cardiovascular diseases, is characterized by card … tal role in regulating apoptosis and hypertrophy. Notably, Bmal1 is a key upstream regulator of p53 ubiquitination. Therefore, targeting the Bmal1-p53 degradation axis offers a novel therapeutic approach to alleviate cardiomyocyte apoptosis and hypertrophy. AIM OF THE STUDY: This study aims to validate whether QHZYF mitigates cardiomyocyte apoptosis and hypertr …

Integrating machine learning for the identification of ubiquitination-associated genes in moyamoya disease.

INTRODUCTION: Moyamoya disease (MMD) is an infrequent cerebrovascular disorder typified by bilateral internal carotid artery obstruction, yet its pathogenic mechanism remains elusive. This study examines the role of epigenetic ubiquitination-related genes in MMD. METHODS: We utilized two datasets (GSE157628 and GSE141024) from the GEO database and sourced ubiquitination-related genes from the GeneCards database. Differentially expressed genes were identified, followed by Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) to elucidate ke…

Legionella pneumophila Effector Protein LegU1 Mediates the Ubiquitination of Endoplasmic Reticulum Chaperone BiP.

The facultative intracellular pathogen Legionella pneumophila, which causes Legionnaires' disease, translocates over 300 effector proteins i … BiP during L. pneumophila infection. We finally indicate that LegU1 interacts with and mediates the ubiquitinational degradation of BiP. Altogether, our study identifies BiP as a new substrate of LegU1 and provides new insight into how L. pneumophila modulates the host UPR pathway during infection.

Убиквитационное регулирование гликолитического фермента MCT4 в поощрении астроцитной реактивности во время нейроинфламмации.

Одним из гистопатологических признаков нервно-воспалительных заболеваний, таких, как множественный склероз (MS), является появление астроцитной реактивности. Накопление данных свидетельствует о том, что чрезмерный гликолиз может привести к астроцитной реактивности и способствовать нейроэнфламативным реакциям. Однако сложные механизмы, лежащие в основе метаболического перепрограммирования астроцитов в направлении гликолиза, остаются в значительной степени неизвестными. Здесь мы провели эксперименты in vitro с использованием первичных астроцитов и в vivo в экспериментальной аутоиммунной энцефало

Совпадение в аннотации оригинала
One of the histopathological hallmarks of neuroinflammatory diseases such as multiple sclerosis (MS) is the emergence of astrocyte reactivit … eport a novel regulatory mechanism in which the E3 ubiquitin ligase TRIM7 regulates MCT4 levels via ubiquitination. In mice, blockade of astrocyte MCT4 expression by intracerebroventricular injection of lentivirus alleviated disease severity of EAE mice. The results suggest that targeting glycolysis, specifically through the inhibition of MCT4 expression, might …

LOXL1-AS1 inhibits JAK2 ubiquitination and promotes cholangiocarcinoma progression through JAK2/STAT3 signaling.

This study thoroughly investigated the role of the long non-coding RNA LOXL1-AS1 in the pathogenesis of cholangiocarcinoma (CCA). Through bi … T3 signaling pathway. Notably, LOXL1-AS1 might regulate the activity of JAK2 through modulating its ubiquitination and degradation. YY1 had also been found to act as an upstream transcription factor of LOXL1-AS1 to impact CCA cell malignancy. These findings shed light on the pivotal role of LOXL1-AS1 in CCA and offered potential directions for novel therapeutic …

NS1 binding protein regulates stress granule dynamics and clearance by inhibiting p62 ubiquitination.

The NS1 binding protein, known for interacting with the influenza A virus protein, is involved in RNA processing, cancer, and nerve cell gro … ed in autophagy. In cells lacking NS1 binding protein, stress granule dynamics are altered, and p62 ubiquitination is increased, suggesting impaired stress granule degradation. Overexpression of NS1 binding protein reduces p62 ubiquitination. In amyotrophic lateral sclerosis patient-derived neurons, reduced NS1 binding protein and p62 disrupt stress granule morp …

The prognostic significance of ubiquitination-related genes in multiple myeloma by bioinformatics analysis.

BACKGROUND: Immunoregulatory drugs regulate the ubiquitin-proteasome system, which is the main treatment for multiple myeloma (MM) at present. In this study, bioinformatics analysis was used to construct the risk model and evaluate the prognostic value of ubiquitination-related genes in MM. METHODS AND RESULTS: The data on ubiquitination-related genes and MM samples were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The consistent cluster analysis and ESTIMATE algorithm were used to create distinct clusters. The MM prognostic risk model was constr…

c-Cbl induced podocin ubiquitination contributes to the podocytes injury in diabetic nephropathy.

The ubiquitination function in diabetic nephropathy (DN) has attracted much attention, but there is a lack of information on its ubiquitylome profile. To examine the differences in protein content and ubiquitination in the kidney between db/db mice and db/m mice, we deployed liquid chromatography-mass spectrometry (LC-MS/MS) to conduct analysis. We determined 145 sites in 86 upregulated modified proteins and 66 sites in 49 downregulated modified proteins at the ubiquitinated level. Moreover, 347 sites among the 319 modified proteins were present only in the db/db mouse kidneys, while 213 sites…

Toxoplasma gondii ROP5 Enhances Type I IFN Responses by Promoting Ubiquitination of STING.

Toxoplasma gondii is a widely spread opportunistic pathogen that can infect nearly all warm-blooded vertebrates and cause serious toxoplasmo … -dependent manner. Additionally, ROP5 strengthened cGAS-STING signaling by enhancing the K63-linked ubiquitination of STING. Consistently, ROP5 deficient PRU (PRUΔROP5) induced fewer type I IFN-related immune responses and replicated faster than the parental strain in RAW264.7 cells. Taken together, this study provides new insights into the mechanism by which RO …

The role of mesenchymal stem cells in attenuating inflammatory bowel disease through ubiquitination.

Inflammatory bowel disease (IBD), a condition of the digestive tract and one of the autoimmune diseases, is becoming a disease of significant global public health concern and substantial clinical burden. Various signaling pathways have been documented to modulate IBD, but the exact activation and regulatory mechanisms have not been fully clarified; thus, a need for constant exploration of the molecules and pathways that play key roles in the development of IBD. In recent years, several protein post-translational modification pathways, such as ubiquitination, phosphorylation, methylation, acety…

Malat1 regulates PMN-MDSC expansion and immunosuppression through p-STAT3 ubiquitination in sepsis.

Myeloid-derived suppressor cells (MDSCs) expand during sepsis and contribute to the development of persistent inflammation-immunosuppression-catabolism syndrome. However, the underlying mechanism remains unclear. Exploring the mechanisms of MDSCs generation may provide therapeutic targets for improving immune status in sepsis. Here, a sepsis mouse model is established by cecal ligation and perforation. Bone marrow cells at different sepsis time points are harvested to detect the proportion of MDSCs and search for differentially expressed genes by RNA-sequence. In lethal models of sepsis, polym

Progranulin deficiency associates with postmenopausal osteoporosis via increasing ubiquitination of estrogen receptor α.

Estrogen deficiency is considered the most important cause of postmenopausal osteoporosis. However, the underlying mechanism is still not co … r involved in estrogen regulation of osteoporosis, through enhancing its degradation via K48-linked ubiquitination. These findings not only provide a previously unrecognized interplay between PGRN and estrogen signaling in regulating osteoclastogenesis and osteoporosis but may also present a new therapeutic approach for the prevention and treatment of postmenopa …

Utilizing Ubiquitination Patterns to Predict Prostate Cancer Prognosis and Devise a Therapeutic Response.

BACKGROUND: Ubiquitination, a post-translational modification, is crucial for cancer regulation. However, the predictive significance of ubiquitination-related genes (URGs) for prostate adenocarcinoma (PRAD) remains unclear. OBJECTIVES: The objectives of the study were to investigate the role of URGs in PRAD and their potential impact on patient prognosis. METHODS: This study acquired data for more than 800 patients with PRAD from public databases. The unique ubiquitination-related patterns of PRAD were detected by unsupervised clustering approach. URGs relevant to the prognosis of patients …

Ubiquitination-related biomarkers in metastatic melanoma patients and their roles in tumor microenvironment.

BACKGROUND: Skin cutaneous melanoma (SKCM) is the deadliest type of cutaneous malignancy. Ubiquitination is a process of protein sorting and degradation that exhibits multiple functions in the progression of various tumors. This study aimed to characterize a set of genes for ubiquitination in SKCM. METHODS: The expression patterns of ubiquitin-associated genes (URGs) and the corresponding clinical information in SKCM tissues were comprehensively analyzed based on The Cancer Genome Atlas (TCGA) database. We performed univariate and multivariate Cox proportional regression models to characteriz…

Identification and validation of a novel ubiquitination-related gene UBE2T in Ewing's sarcoma.

BACKGROUND: Ewing's sarcoma (ES) is one of the most prevalent malignant bone tumors worldwide. However, the molecular mechanisms of the genes and signaling pathways of ES are still not well sufficiently comprehended. To identify candidate genes involved in the development and progression of ES, the study screened for key genes and biological pathways related to ES using bioinformatics methods. METHODS: The GSE45544 and GSE17618 microarray datasets were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified, and functional enrichment a

Hydralazine represses Fpn ubiquitination to rescue injured neurons via competitive binding to UBA52.

A major impedance to neuronal regeneration after peripheral nerve injury (PNI) is the activation of various programmed cell death mechanisms … ury site induces neuronal ferroptosis by increasing intracellular iron via accelerated UBA52-driven ubiquitination and degradation of Fpn, and stimulation of lipid peroxidation. Early administration of the potent arterial vasodilator, hydralazine (HYD), decreases the ubiquitination of Fpn after PNI by binding to UBA52, leading to suppression of neuronal cell dea …

A Double Hit to Ubiquitination Leading to a New Diagnosis of VEXAS Syndrome.

VEXAS (vacuoles, E1 enzyme, X-linked, auto-inflammatory, somatic) syndrome is a newly defined illness that bridges hematology, oncology, and rheumatology. Its pathophysiology originates in a mutation in the UBA1 gene that leads to a defect in ubiquitination resulting in a severe systemic inflammatory syndrome. It is associated with significant morbidity and mortality; however, data are scarce due to limited cases described in the literature. Here we describe a case of a male in his 60s who was referred to hematology-oncology due to progressive dyspnea, poor oral intake, and weight loss. He was…

Targeting WWP1 ameliorates cardiac ischemic injury by suppressing KLF15-ubiquitination mediated myocardial inflammation.

Rationale: Previous studies have suggested that myocardial inflammation plays a critical role after ischemic myocardial infarction (MI); how … iggered excessive cardiomyocyte inflammation after MI by targeting KLF15 to catalyze K48-linked polyubiquitination and degradation. Ultimately, WWP1-mediated degradation of KLF15 contributed to the up-regulation of p65 acetylation, and activated the inflammatory signaling of MAPK in ischemic myocardium and hypoxia-treated cardiomyocytes. Thus, targeting of WWP1 …

CHIP induces ubiquitination and degradation of HMGB1 to regulate glycolysis in ovarian endometriosis.

Ovarian endometriosis is a common gynecological condition that can cause infertility in women of childbearing age. However, the pathogenesis is still unknown. We demonstrate that the carboxyl terminus of Hsc70-interacting protein (CHIP) is a negative regulator in the development of endometriosis and reduces HMGB1 expression in endometriotic cells. Meanwhile, CHIP interacts with HMGB1 and promotes its ubiquitinated degradation, thereby inhibiting aerobic glycolysis and the progression of endometriosis. Furthermore, the CHIP agonist YL-109 effectively suppresses the growth of ectopic endometrium