OGA (O-GlcNAcase)

Moreover, the RAGE antagonist FPS-ZM1 synergized with gemcitabine to suppress tumor progression. Collectively, these findings uncover an EV-mediated crosstalk between GBC cells and neurons in which RIPK1-dependent necroptosis and its effector HMGB1 drive PNI, positioning the HMGB1-RAGE axis as a tractable therapeutic target.

Together, these findings define a Gpxl-O-GlcNAc-DDR axis that integrates lipid-peroxidation defense with nutrient and stress signaling to maintain epithelial homeostasis during aging and oxidative stress. By identifying Gpxl as a required node in O-GlcNAc-dependent proliferative programs, our work nominates this axis as a tractable therapeutic target for age-associated intestinal dysfunction and neoplastic progression.

In this review, we discuss key interactors and their functional impact on OGT. We also explore how post-translational modifications and substrate availability contribute to OGT regulation and specificity.

New perspectives and research directions are also discussed. Such information is expected to facilitate the rational design of novel modulators of OGT and OGA to enable more specific functional control and potential treatment of disease.

To date, no patients with OGT-CDGs have been reported with hepatoblastoma or other malignancies. Although the occurrence of hepatoblastoma in the proband might be coincidental, the role of O-GlcNAcylation in cancer suggests that the deficiency of OGT activity might be associated with increased cancer risk.

Stabilization and enhancement of O-GlcNAcylation improve the target-killing capacity of NK cells while overcoming suppressive factors in the TME. These findings highlight advanced strategies, including genetic engineering of O-GlcNAc pathways, as potent approaches to augment NK-based immunotherapies against cancer.

This report expands the molecular spectrum of MIFS and highlights the diagnostic utility of advanced sequencing technologies in identifying rare gene fusions. The TRIM24::BRAF fusion may represent a potential therapeutic target, warranting further investigation.

Functional improvements translated in enhanced recognition memory in Ts2Cje mice. Our study highlights the pivotal role of altered protein O-GlcNAcylation in DS neuropathology and establishes the molecular basis to envision the O-GlcNAc process as a promising therapeutic target to mitigate genetic- and metabolism-driven brain alterations linked to redox imbalance, mitochondrial failure and the development of AD features.

NF-κB overexpression reversed the effects of 5-MTP in vitro and in vivo. Our results demonstrate that 5-MTP ameliorated CKD-induced cerebrovascular injury through the NF-κB pathway, indicating its potential as an innovative and efficacious therapeutic target for CKD-induced cerebrovascular dysfunction.

We then validated this model by studying YEATS domain containing 2 (YEATS2) from the protein pool, and demonstrated that YEATS2 is SUMOylated at K592, targeting it to CMA. Our work uncovers the SUMO-SIM interaction as a fundamental mechanism governing CMA substrate selectivity and identifies a potential CMA client proteome to deepen our understanding of its pathophysiological relevance.

We show that dynamic O-GlcNAcylation is a negative regulator of mRNA biosynthesis and propose that the addition and removal of the modification serve as quality control-steps to ascertain successful generation of mature mRNAs. Our work identifies unprecedented redundancy in the regulation of RNA Pol II, which increases resilience towards transcriptional stress, and also underscores the difficulty of targeting transcription to control cancer.

Additionally, gene enrichment analysis revealed the involvement of these DEGs in key biological processes, including intracellular trafficking and myeloid progenitor cell differentiation. These findings emphasize the potential of SP3, CSNK1A1, STYX, SIRT5, and MGEA5 as biomarkers and therapeutic targets in DLBC, particularly highlighting STYX as a promising prognostic marker and potential target for therapeutic intervention.