TRIM25: A Global Player of Cell Death Pathways and Promising Target of Tumor-Sensitizing Therapies

Cells, Год журнала: 2025, Номер 14(2), С. 65 - 65

Опубликована: Янв. 7, 2025

Therapy resistance still constitutes a common hurdle in the treatment of many human cancers and is major reason for failure patient relapse, concomitantly with dismal prognosis. In addition to “intrinsic resistance”, e.g., acquired by random mutations, cancer cells typically escape from certain treatments (“acquired resistance”) large variety means, including suppression apoptosis other cell death pathways via upregulation anti-apoptotic factors or through inhibition tumor-suppressive proteins. Therefore, ideally, tumor-cell-restricted induction considered promising avenue development novel, tumor (re)sensitizing therapies. A growing body evidence has highlighted multifaceted role tripartite motif 25 (TRIM25) controlling different aspects tumorigenesis, chemotherapeutic drug resistance. Accordingly, overexpression TRIM25 observed tumors frequently correlates poor survival. its originally described function antiviral innate immune response, can play critical yet context-dependent roles apoptotic- non-apoptotic-regulated pathways, pyroposis, necroptosis, ferroptosis, autophagy. The review summarizes current knowledge molecular mechanisms which interfere modalities thereby affect success currently used chemotherapeutics. better understanding complex repertoire modulatory effects an essential prerequisite validating as potential target future anticancer therapy surmount high rate chemotherapies.

Язык: Английский

---

RNF128 deficiency in macrophages promotes colonic inflammation by suppressing the autophagic degradation of S100A8

Cell Death and Disease, Год журнала: 2025, Номер 16(1)

Опубликована: Янв. 15, 2025

Abstract Macrophages play important roles in maintaining intestinal homeostasis and the pathogenesis of inflammatory bowel diseases (IBDs). However, underlying mechanisms that govern macrophage-mediated inflammation are still largely unknown. In this study, we report RNF128 is downregulated proinflammatory macrophages. deficiency leads to elevated levels effector cytokines vitro accelerates progression IBD mouse models. Bone marrow transplantation experiments revealed bone cells contributes worsening DSS-induced colitis. Mechanistically, interacts with destabilizes S100A8 by promoting its autophagic degradation, which mediated cargo receptor Tollip. Moreover, administration an neutralizing antibody mitigated development colitis improved survival DSS-treated Rnf128 −/− mice. Overall, our study underscores anti-inflammatory role macrophages during highlights potential targeting RNF128-Tollip-S100A8 axis attenuate for treatment

Язык: Английский

---

TRIM11 modulates sepsis progression by promoting HOXB9 ubiquitination and inducing the NF-κB signaling pathway

Molecular Biology Reports, Год журнала: 2025, Номер 52(1)

Опубликована: Фев. 4, 2025

Язык: Английский

---

Neurodegenerative diseases and neuroinflammation-induced apoptosis

Open Life Sciences, Год журнала: 2025, Номер 20(1)

Опубликована: Янв. 1, 2025

Abstract Neuroinflammation represents a critical pathway in the brain for clearance of foreign bodies and maintenance homeostasis. When neuroinflammatory process is dysregulate, such as over-activation microglia, which results excessive accumulation free oxygen inflammatory factors brain, among other factors, it can lead to an imbalance homeostasis development various diseases. Recent research has indicated that numerous neurodegenerative diseases closely associated with neuroinflammation. The pathogenesis neuroinflammation intricate, involving alterations genes proteins, well activation inhibition signaling pathways. Furthermore, inflammation result neuronal cell apoptosis, further exacerbate extent disease. This article presents summary recent studies on relationship between apoptosis caused by aim identify link two provide new ideas targets exploring pathogenesis, prevention treatment

Язык: Английский

---

Mechanisms and Therapeutic Strategies for NLRP3 Degradation via Post-Translational Modifications in Ubiquitin-proteasome and Autophagy Lysosomal Pathway

European Journal of Medicinal Chemistry, Год журнала: 2025, Номер 289, С. 117476 - 117476

Опубликована: Март 4, 2025

Язык: Английский

---

Inhibition of the expression of TRIM63 alleviates ventilator-induced diaphragmatic dysfunction by modulating the PPARα/PGC-1α pathway

Mitochondrion, Год журнала: 2025, Номер unknown, С. 102025 - 102025

Опубликована: Март 1, 2025

Язык: Английский

---

TRIM38 Suppresses the Progression of Colorectal Cancer via Enhancing CCT6A Ubiquitination to Inhibit the MYC Pathway

Advanced Science, Год журнала: 2025, Номер unknown

Опубликована: Март 6, 2025

Emerging evidence reveals the pivotal function of tripartite motif protein (TRIM) in colorectal cancer (CRC). However, precise TRIM38 and its underlying mechanism CRC remains to be elucidated, especially regarding putative ubiquitination function. Here, it is identified that downregulated tissues by DNA hypermethylation promoter. Further analysis demonstrates decreased correlated with unfavorable clinical features poor prognosis. Moreover, functions as a tumor suppressor inhibiting cell proliferation, metastasis, AOM/DSS-induced tumorigenesis cells. Mechanistically, binds substrate CCT6A, leading degradation K48-linked CCT6A at K127/K138 residues. The elevation level caused downregulation diminishes c-Myc protein, thereby activating MYC pathway. study elucidates novel TRIM38/CCT6A/c-Myc axis regulating CRC, potentially offering new therapeutic target for treatment.

Язык: Английский

---

Spatial transcriptomics identifies novel Pseudomonas aeruginosa virulence factors

Cell Genomics, Год журнала: 2025, Номер 5(3), С. 100805 - 100805

Опубликована: Март 1, 2025

Highlights•Spatial transcriptome analysis captures host and pathogen signatures•Integrating spatial data allows the prediction of bacterial burden at infected sites•Transcript enrichment highlights virulence mechanismsSummaryTo examine host-pathogen interactions, we leveraged a dual transcriptomics approach that simultaneously expression Pseudomonas aeruginosa genes alongside entire using murine model ocular infection. This method revealed differential pathogen- host-specific gene patterns in corneas, which generated unified transcriptional map By integrating these data, developed predictive ridge regression trained on images from tissues. The achieved an R2 score 0.923 predicting distributions identifying novel biomarkers associated with disease severity. Among iron acquisition pathogen-specific transcripts showed significant interface, discovered mediator PA2590, was required for virulence. study therefore power combining to uncover complex interactions identify potentially druggable targets.Graphical abstract

Язык: Английский

---

The B30.2/SPRY-Domain: A Versatile Binding Scaffold in Supramolecular Assemblies of Eukaryotes

Crystals, Год журнала: 2025, Номер 15(3), С. 281 - 281

Опубликована: Март 19, 2025

B30.2 domains, sometimes referred to as PRY/SPRY were originally identified by sequence profiling methods at the gene level. The domain comprises a concanavalin A-like fold consisting of two twisted seven-stranded anti-parallel β-sheets. domains are present in about 150 human and 700 eukaryotic proteins, usually fused other domains. represents scaffold, which, through six variable loops, binds different unrelated peptides or endogenous low-molecular-weight compounds. At cellular level, proteins engage supramolecular assemblies with important signaling functions. In humans, often found E3-ligases, such tripartite motif (Trim) SPRY domain-containing SOCS box Ran binding protein 9 −10, Ret-finger protein-like, Ring-finger proteins. recognizes target recruits E2-conjugase means involving specific adaptor Further well-studied methyltransferase Ash2L, some butyrophilins, Ryanodine Receptors. Although affinity an isolated its ligand might be weak, it can increase strongly due avidity effects upon recognition oligomeric targets context macromolecular machines.

Язык: Английский

---

TRIM21 promotes type I interferon by inhibiting the autophagic degradation of STING via p62/SQSTM1 ubiquitination in systemic lupus erythematosus

Acta Biochimica et Biophysica Sinica, Год журнала: 2025, Номер unknown

Опубликована: Март 1, 2025

The cGAS-STING signaling pathway serves as a pivotal surveillance mechanism for cytosolic double-stranded DNA (dsDNA) detection in mammalian systems. While STING-mediated type I interferon production is crucial host defense, sustained activation of this contributes to autoimmune pathologies, including systemic lupus erythematosus (SLE). Maintaining immune homeostasis requires precise regulation STING activity prevent hyperactivation. Our study identifies TRIM21 novel positive regulator SLE pathogenesis. results demonstrate that overexpression stabilizes by suppressing autophagic degradation, whereas depletion accelerates clearance process. Mechanistically, catalyzes the K63-linked polyubiquitylation selective autophagy receptor p62/SQSTM1, disrupting its interaction with STING. This post-translational modification prevents sequestration into autophagosomes, thereby stabilizing adaptor protein and amplifying downstream responses. findings reveal previously unrecognized regulatory circuit which orchestrates cross-talk between ubiquitin control turnover. TRIM21-p62 axis represents potential therapeutic target attenuating pathological STING-dependent disorders. work advances our understanding demonstrating how E3 ligase-mediated modifications modulate cargo recognition pathways. identified provides new insights molecular interplay ubiquitylation degradation maintaining innate balance, offering perspectives developing targeted therapies against interferonopathies associated hyperactivity.

Язык: Английский

---