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Bioinformatics and Machine Learning-Based Identification of Critical Biomarkers and Immune Infiltration in Venous Thromboembolism.

Objective: This study aims to use bioinformatics and machine learning algorithms to screen and analyze the key genes involved in venous thro … s (DEGs) were discovered between the VTE samples and normal samples. GO analysis identified protein polyubiquitination, lysosomal lumen acidification, organellar ribosome, mitochondrial ribosome, ammonium transmembrane transporter activity, and immunoglobulin binding as the processes with the highest abundance of DEGs. KEGG pathway analysis revealed that DEGs w …

20-hydroxyecdysone suppresses bladder cancer progression via inhibiting USP21: A mechanism associated with deubiquitination and degradation of p65.

Bladder cancer is one of the most common malignancies of the urinary tract and a prevalent cancer worldwide, still requiring efficient thera … es showed that USP21 directly interacted with and stabilized p65 by deubiquitinating its K48-linked polyubiquitination in bladder cancer cells, which could be abolished by 20-HE treatment, contributing to p65 degradation. Finally, we found that USP21 overexpression could not only facilitate the proliferation, migration, and invasion of bladder cancer cells, but …

USP20 deletion promotes eccentric cardiac remodeling in response to pressure overload and increases mortality.

Left ventricular hypertrophy (LVH) caused by chronic pressure overload with subsequent pathological remodeling is a major cardiovascular ris … antly reduced in USP20-KO after TAC. Mechanistically, we identified increased degradative lysine-48 polyubiquitination of MYH7 in USP20-KO hearts, indicating that USP20-mediated deubiquitination likely prevents protein degradation of MYH7 during pressure overload. Our findings suggest that USP20-dependent signaling pathways regulate the layering pattern of sarc …

TRIM59 alleviates neuronal ferroptosis and promotes functional recovery after spinal cord injury by mediating ubiquitination and degradation of ANXA2.

BACKGROUND: Spinal cord injury (SCI) is a severe central nervous system disorder for which effective therapeutic interventions remain limite … urological restoration. Mechanistically, TRIM59 directly bound to ANXA2 and mediated its K48-linked polyubiquitination and subsequent proteasomal degradation. The neuroprotective effect of TRIM59 was abolished by a catalytically inactive C30A mutant or by ANXA2 overexpression, whereas ANXA2 knockdown rescued the ferroptosis and functional deficits induced by TR …

TIGAR Maintains Mitotic Spindle Organization and βII-Tubulin Stability in Glioma Stem Cells.

BACKGROUND: Glioblastoma (GBM) is a highly aggressive brain malignancy driven by glioma stem cells (GSCs). TIGAR (TP53-induced glycolysis an … o the mitotic spindle and physically interacts with βII-tubulin, protecting it from Parkin-mediated polyubiquitination and subsequent proteasomal degradation. NAC failed to rescue βII-tubulin loss after TIGAR knockdown, whereas Parkin co-depletion restored βII-tubulin levels and partially normalized the G2/M fraction. In vivo, TIGAR knockdown inhibited GSC-driv …

FBXO5 regulates RPL23A to promote MDM2-mediated p53 degradation and facilitate malignant progression of breast cancer.

BACKGROUND: Breast cancer (BC) is one of the most common malignant tumors in women worldwide, with metastasis and recurrence constituting ma … ments confirmed that FBXO5 directly interacts with ribosomal protein L23a (RPL23A) and promotes its polyubiquitination at the K48 chain, thereby regulating its degradation. Further experiments showed that the ubiquitination-mediated degradation of RPL23A led to a decrease in the stability of Tumor Protein p53(p53) and facilitated its degradation by Proto-Oncoge …

Pterostilbene mitigates intervertebral disc degeneration via dual regulation of mitophagy and NLRP3 ubiquitination to inhibit nucleus pulposus cell pyroptosis.

BACKGROUND: Intervertebral disc degeneration (IVDD) is a major contributor to low back pain and is characterized by mitochondrial dysfunctio … E facilitated ubiquitination and proteasomal degradation of NLRP3, predominantly through K48-linked polyubiquitination, while K63-linked modification may contribute to regulatory signaling. Notably, this ubiquitination-mediated degradation occurred independently of mitophagy. In vivo, PTE significantly alleviated disc degeneration, reduced NLRP3, caspase-1, and …

The deubiquitinase OTULIN regulates tau expression and RNA metabolism in neurons.

The degradation of aggregation-prone tau is regulated by the ubiquitin-proteasome system (UPS) and autophagy, which are impaired in Alzheime … SH-SY5Y resulted in a complete loss of tau at both mRNA and protein levels, and increased levels of polyubiquitinated proteins, which are being degraded by the proteasome as confirmed with an inhibitor, Lactacystin. In addition, SH-SY5Y OTULIN KO cells showed downregulation of various genes associated with inflammation, autophagy, ubiquitin-proteasome system, a …

Tumorigenesis of basal muscle invasive bladder cancer was mediated by PTEN protein degradation resulting from SNHG1 upregulation.

BACKGROUND: Phosphatase and tensin homolog deleted on chromosome ten (PTEN) serves as a powerful tumor suppressor, and has been found to be … subsequent decrease in USP8 protein expression. The downregulation of USP8, in turn, increased PTEN polyubiquitination and degradation, culminating in cell malignant transformation and BMIBC anchorageindependent growth. In vivo studies confirmed the downregulation of PTEN and USP8, as well as their positive correlations in both BBN-treated mouse bladder urothel …

Hepatitis B surface antigen impairs TLR4 signaling by upregulating A20 expression in monocytes.

UNLABELLED: Toll-like receptors (TLRs) play a crucial role in eliminating viral infection. Conversely, viruses have evolved various strategi … suggesting that HBsAg can block downstream TLR4 signaling. Furthermore, we proved that LPS-induced polyubiquitination of tumor necrosis factor receptor-associated factor 6 (TRAF6) and the formation of the TRAF6-TAB2 complex were inhibited in HBsAg-pretreated cells. Interestingly, HBsAg led to a significant upregulation of A20, a ubiquitin-editing enzyme. Corre …

METTL5 stabilizes c-Myc by facilitating USP5 translation to reprogram glucose metabolism and promote hepatocellular carcinoma progression.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most prevalent cancers in the world, with a high likelihood of metastasis and a dis … ) regions of ubiquitin specific peptidase 5 (USP5) binded to c-Myc protein and inhibited K48-linked polyubiquitination of c-Myc. Further study revealed that METTL5 controled the USP5 translation process, which in turn regulated the ubiquitination of c-Myc. Furthermore, we identified cAMP responsive element binding protein 1 (CREB1)/P300 as a critical transcript …

Interleukin-1β drives NEDD8 nuclear-to-cytoplasmic translocation, fostering parkin activation via NEDD8 binding to the P-ubiquitin activating site.

BACKGROUND: Neuroinflammation, typified by elevated levels of interleukin-1 (IL-1) α and β, and deficits in proteostasis, characterized by accumulation of polyubiquitinated proteins and other aggregates, are associated with neurodegenerative disease independently and through interactions of the two phenomena. We investigated the influence of IL-1β on ubiquitination via its impact on activation of the E3 ligase parkin by either phosphorylated ubiquitin (P-Ub) or NEDD8. METHODS: Immunohistochemistry and Proximity Ligation Assay were used to assess colocalization of parkin with P-tau or NEDD8 in…

A Plastid Protein That Evolved from Ubiquitin and Is Required for Apicoplast Protein Import in Toxoplasma gondii.

Apicomplexan parasites cause a variety of important infectious diseases, including malaria, toxoplasma encephalitis, and severe diarrhea due … biquitin conjugation onto target proteins are essential for this function, while those required for polyubiquitination and preprotein processing are dispensable. Our experiments provide a mechanistic understanding of the molecular machinery that drives protein import across the membranes of the apicoplast.IMPORTANCE Apicomplexan parasites are responsible for im …

Ubiquitination-deubiquitination by the TRIM27-USP7 complex regulates tumor necrosis factor alpha-induced apoptosis.

Tumor necrosis factor alpha (TNF-α) plays a role in apoptosis and proliferation in multiple types of cells, and defects in TNF-α-induced apoptosis are associated with various autoimmune diseases. Here, we show that TRIM27, a tripartite motif (TRIM) protein containing RING finger, B-box, and coiled-coil domains, positively regulates TNF-α-induced apoptosis. Trim27-deficient mice are resistant to TNF-α-d-galactosamine-induced hepatocyte apoptosis. Trim27-deficient mouse embryonic fibroblasts (MEFs) are also resistant to TNF-α-cycloheximide-induced apoptosis. TRIM27 forms a complex with and ubiqu

UBE2C-TRIM21-driven NOS2 degradation stabilizes Tregs and suppresses pyroptotic signaling in thyrocytes in Hashimoto's thyroiditis.

BACKGROUND: Hashimoto's thyroiditis (HT) features persistent immune intolerance and progressive thyrocyte injury, yet the mechanistic linkag … a UBE2C-interacting E3 ligase partner that cooperated with UBE2C to drive predominantly K48-linked polyubiquitination and proteasomal degradation of NOS2 (with K516 as a key acceptor site). NOS2 accumulation impaired Treg mitochondrial membrane potential and shifted bioenergetics toward glycolysis, undermining Treg stability and restoring thyrocyte inflammasom …

USP7-dependent stabilization of FKBP4 contributes to acquired osimertinib resistance through glycolytic remodeling in NSCLC.

Osimertinib is the standard first-line epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) for EGFR-mutant non-small-cel … FKBP4 protein abundance without affecting its mRNA, accelerated FKBP4 turnover, and increased FKBP4 polyubiquitination, whereas wild-type USP7—but not a catalytically inactive mutant—suppressed FKBP4 ubiquitination. In vivo, FKBP4 silencing enhanced the antitumor effect of osimertinib in resistant xenografts and mitigated EMT features. These findings support a …

Targeting Cathepsin B with p-coumaric acid rescues WWP1-dependent proteasomal degradation of NLRP3 in hyperuricemic nephropathy.

BACKGROUND: Hyperuricemic nephropathy (HN) is a prevalent metabolic disorder characterized by tubulointerstitial inflammation and fibrosis, … in protein ligase 1 (WWP1) protein abundance/stability, thereby impairing WWP1-dependent K48-linked polyubiquitination and proteasomal clearance of NLRP3 and promoting inflammasome activation. p-CA-mediated CTSB inhibition preserves WWP1 protein abundance, restores NLRP3 proteasomal clearance, and attenuates downstream pyroptosis, inflammation, and fibrogenesis …

Equine arteritis virus Nsp10 promotes MAVS proteasomal degradation via E3 ligases Smurf1/MARCH5.

Equine arteritis virus (EAV) is a positive-sense, single-stranded RNA virus that belongs to the family Arteriviridae, which also includes po … n. By screening, we found that the E3 ubiquitin ligases Smurf1 and MARCH5 are recruited by nsp10 to polyubiquitinate and degrade MAVS. Interestingly, the degradation of MAVS promoted by nsp10 depends on the dimerization of nsp10, which occurs through the interactions of zinc finger motifs. The CARD or PRR domain of MAVS and the 1A domain of nsp10 are responsibl …

Targeting E3 Ubiquitin Ligase Hrd1 Prevents Myocardial Ischemia-Reperfusion Injury Through Enhancing ALDH2 Enzymatic Activity.

BACKGROUND: Myocardial ischemia-reperfusion (I/R) injury presents a significant clinical challenge characterized by a complex pathological m … infiltration of inflammatory cells after I/R injury. Mechanistically, Hrd1 promoted the K33-linked polyubiquitination of ALDH2 and then inhibited the formation of its active tetramers, which reduced the apoptosis of CD45+ ECs and exacerbated endothelial dysfunction through the NO/cGMP/PKG (nitric oxide-cyclic guanosine monophosphate-protein kinase G) signaling …

Вирус Западного Нила и вирусные инфекции Зики вызывают резкие образования в гениальных потомках человека и в клетках A549.

UNLABELELED: Ранее было замечено, что вирусные репликации зики (VRV) имеют асимметричное скопление с одной стороны ядра в инфицированных Huh7, A549 и h-NPC. Инфекции вируса Западного Нила (ВНВ) в этих клетках также вызывают асимметричное группирование VRV. Были исследованы последовательные ответы ячеек, ведущие к асимметричной группировке ВНВ и ЗИКВ VRV. Обе инфекции активировали белковую реакцию на клетку (УПО), о чем свидетельствует усиление ПРФ78, главного регулятора УПО, и активация отделения ПЕРК УПО (p-PERK-p-eIF2α-GADD34). Кроме того, был вызван рост ацетилации микротубуля (MT). По мере

Совпадение в аннотации оригинала
UNLABELLED: Zika viral replication vesicles (VRVs) were previously observed to cluster asymmetrically on one side of the nucleus in infected … h excessive misfolded proteins when the UPR is overwhelmed. During aggresome formation, HDAC6 links polyubiquitinated proteins to the dynein motor complex for transport along MTs to the MTOC, where they aggregate and are surrounded by a vimentin cage. HDAC6 knockdown prevented asymmetric clustering of viral replication complexes, resulted in activation of the p …