CUL2 (Cullin 2)

Our findings reveal a novel mechanism whereby CUL2 promotes PC progression and ferroptosis resistance through regulation of the KEAP1-NRF2 axis. CUL2 overexpression enhances cellular antioxidant capacity and maintains mitochondrial integrity, thereby conferring broad resistance to ferroptosis-inducing conditions. This study suggests that targeting the CUL2-NRF2 axis to enhance ferroptosis sensitivity might represent a promising therapeutic strategy for PC treatment.

Notably, PRDX1 knockout macrophages inhibited syngeneic tumor growth and enhanced sensitivity to anti-PD-1 therapy in vivo. In conclusion, targeted deletion of PRDX1 enhances anti-tumor immunity in CRC by reprogramming the immunosuppressive TAMs, revealing a novel role of PRDX1 as a potential drug target during anti-tumor immunotherapy.

This study developed a 14-gene consensus prognosis-related signature validated for robust prognostic performance across cohorts. CUL2, identified as a pivotal protective biomarker in melanoma, demonstrates potent tumour-suppressive activity through significant inhibition of proliferation and migration potential.

These findings indicate that the p.E92G ELOC variant is responsible for the VHL manifestations in this family, and that these tumors are being driven by loss of the VCB-Cul2 E3-ubiquitin ligase complex activity.

This study provides novel insight into the role of cullin genes in READ, suggesting that CUL2 and CUL7 may be biomarkers and therapeutic targets. Further research is warranted to explore their underlying mechanisms and clinical applications in READ management.

Flow cytometry revealed significant ROS production, followed by mitochondrial membrane potential dissipation, and caspase activation, underscoring CuL2+'s mechanism of action. These findings position CuL2+ as a promising candidate for cancer therapy, providing insights into copper complexes' therapeutic application through oxidative stress and apoptosis modulation.

Our recent work demonstrates that WSB1 and WSB2 (WSB1/2), two additional SOCS-box proteins with structurally similar WD40 repeat domains, function as substrate-recognizing subunits of ECSWSB1/2 to specifically mediate the ubiquitination and degradation of chromatin-associated RelA methylated at Lys314/315. In this review, we summarize the discovery and functional importance of ECSSOCS1 and ECSWSB1/2 in terminating NF-κB activity, highlight the distinct molecular mechanisms by which they ubiquitinate chromatin-associated RelA in a modification- and gene-specific manner, and discuss their potential as therapeutic targets for inflammatory diseases and cancer.

Protein Flexibility-Molecular Dynamic (MD) Simulation study indicated that mutations weaken the interaction of VHL with Elongin C, with V170F showing the most significant reduction in binding quality and stability. In conclusion, this study introduces novel genetic data from an understudied population and highlights the impact of VHL mutations on its interaction with Elongin C. These findings contribute to our understanding of the molecular basis of VHL-related pathologies and may guide future therapeutic strategies targeting these interactions.

Based on the increased glucose dependency following neddylation inhibition by MLN4924, we propose a co-targeting strategy with GLUT1 inhibition, which significantly improves therapeutic efficacy in vitro and in vivo models without safety risks. This dual-targeting approach represents a potent new strategy for gastric cancer treatment.

The 3WJ-ZATACs demonstrate in vivo tumor-specific distribution and achieve dual-target degradation, thereby suppressing tumor growth without causing noticeable toxicity. In summary, ZATACs represent a general, modular, and straightforward platform for targeted protein degradation, offering insights into the potential of other untapped E3 ligases.

The genetic variants identified in Iranian patients with RCH may aid in the molecular confirmation of other patients diagnosed with VHL and their at-risk family members. These pioneering results that include detailed structural and functional analysis of a variant's effect on the VHL protein may serve as a model for future studies.

Moreover, the functional mechanisms by which circRNAs contribute to GC pathogenesis and therapeutic resistance warrant further investigation. Advances in circRNAs research could provide valuable insights into the early detection and targeted treatment of GC, ultimately improving patient outcomes.