TRAF6 (TNF Receptor Associated Factor 6)

This study identifies PD-L1 as a previously unrecognized intrinsic driver of NSCLC progression through activation of the TLR-TRAF6-BECN1 autophagy axis and promotion of EMT. Beyond its canonical role in immune evasion, PD-L1 functions as a dual-regulator of tumorigenesis by coordinating autophagy-dependent oncogenic processes. These findings provide novel mechanistic insight and support the therapeutic rationale for targeting PD-L1 not only as an immune checkpoint but also as a key modulator of cancer cell-intrinsic signaling in NSCLC.

Our findings indicated that hsa_circ_0001756 could promote BC malignant progression through the miR-584-5p/TRAF6 signaling axis. Especially, hsa_circ_0001756 in serum holds promise as a biomarker for BC screening and diagnosis.

Trim26 attenuates liver fibrosis by stabilizing EZH2 and regulating macrophage polarization, which reduces HSC activation.

In conclusion, NSUN7 promotes pyroptosis of lung epithelial cells in sepsis-induced ALI by stabilizing TRAF6 in a m5C-dependent manner. These findings suggest that NSUN7 may be a promising therapeutic target for sepsis-induced ALI.

Mechanistically, these protective effects were mediated through inhibition of the TLR4/NF-κB signaling pathway. Overall, Zn glycine emerges as a promising nutritional strategy for preventing inflammation-driven bone loss via modulation of the gut-bone axis.

Mechanistically, CXCL13 attenuated MAPK and NF-κB activation and blocked p65 nuclear translocation in a CXCR5-independent manner by competitively interfering with RANKL-RANK binding and downstream RANK-TRAF6 signaling. These findings identify CXCL13 as a novel suppressor of osteoclastogenesis by interfering with RANKL-RANK signaling, unveiling an unrecognized regulatory role in osteoclast biology and suggesting potential therapeutic relevance for bone loss disorders.

TRAF6 inhibition increased lipid peroxidation, mitochondrial reactive oxygen species (ROS), and Fe2+ accumulation, thereby exacerbating mitochondrial damage and enhancing RAS-selective lethal 3 (RSL3)-induced ferroptosis...PGG bind and degraded TRAF6 efficiently, triggering mitochondrial ferroptosis and robustly suppressing the growth of KRAS-mutant lung cancer, with partial rescue by ferroptosis blockade. These findings uncovered a previously unrecognized TRAF6/AKT-mediated mitochondrial ferroptosis axis and highlighted PGG as a promising candidate against KRAS-mutant lung cancer.

GSDME functions as a tumor suppressor by enhancing radiosensitivity and inhibiting proliferation and migration in ESCC, through the suppression of the NF-κB signaling pathway. These findings nominate GSDME as a promising biomarker and the NF-κB signaling pathway as a therapeutic target for overcoming radioresistance in ESCC.

ALKBH5-modified UC-MSCs Exo reduced TRAF6 expression by demethylating its m6A sites, promoting M2 macrophage polarisation and alleviating DKD progression. These findings suggested that ALKBH5-modified UC-MSCs Exo might represent a promising therapeutic approach for DKD.

Inhibition of the PTBP1-TRAF6 pathway alleviated lung injury, restored macrophage polarization balance, and promoted NETs clearance. PTBP1 enhances TRAF6 expression by stabilizing its mRNA, promoting M1 macrophage polarization and impairing NETs clearance, ultimately aggravating COPD.

Through combinatorial approaches, including immunoprecipitation‒mass spectrometry (IP‒MS), molecular docking, and site-directed mutagenesis, we preliminarily elucidated that PD-L1 likely governs the chemotactic mediators CCL8 and CXCL9 via the TLR4/TRAF6 signaling axis. These findings collectively establish the previously unappreciated regulatory capacity of macrophage-intrinsic PD-L1 in chemokine modulation during sepsis, potentially informing the development of innovative therapeutic strategies targeting immune dysregulation in critical care settings.

AlphaFold-Multimer modelling further showed a symmetric, trimeric coiled-coiled domain with a conserved hydrophobic core. These results provide experimental support for TRAF6 coiled-coiled domain trimerization and help establish a structural framework for understanding how TRAF6 assembles into higher-order structures.