EIF2AK3 (Eukaryotic Translation Initiation Factor 2 Alpha Kinase 3)

The autophagy-related signature independently predicts CRC prognosis and guides immunotherapy strategies.

PERK and ATF6 signaling pathways were activated in patients with AML. Targeting the unfolded protein response pathway may represent a promising therapeutic strategy for patients with AML.

MAMs were isolated from NCI-H295S cells treated with mitotane, the ferroptosis inducer RSL3, or control. In conclusion, locally reduced Q10 in MAM may contribute to impaired respiratory chain activity and free radical excess induced by mitotane. Recruitment of GRIPAP1 protein to MAMs may transduce cell death.

The nomogram constructed by ER score and clinical features showed good predictive performance on LUAD. This study provided new insights into understanding the role of ER stress in LUAD.

Activation of autophagy by rapamycin counteracted the effects of EIF2AK3 knockdown on both autophagy and PI3K/AKT signaling. Consistently, EIF2AK3 silencing in xenograft models enhanced the therapeutic efficacy of DDP by suppressing autophagy and attenuating PI3K/AKT activation. Collectively, our findings indicate that EIF2AK3 is a critical regulator of hypoxia-triggered autophagy in NSCLC, and targeting EIF2AK3-mediated PI3K/AKT signaling may represent a promising strategy to overcome cisplatin resistance.

Therapeutically, IRE1 RNase inhibitors (e.g., MKC-8866, B-I09), PERK/EIF2AK3 pathway modulators, protein-disulfide isomerase inhibition, and agents that trigger irrecoverable ER stress show preclinical efficacy, including synergy with platinum, poly (ADP-ribose) polymerase (PARP) inhibitors, HDAC6 blockers, and PD-1 inhibitors...Thus, ER-stress/UPR signaling is a convergent, targetable axis in gynecologic cancers. Priorities include validating UPR-based prognostic signatures, defining context-specific vulnerabilities (e.g., genotype-informed IRE1/XBP1 dependence), and executing biomarker-driven clinical trials that combine UPR-targeted agents with standard chemotherapy, PARP inhibition, and immunotherapy to overcome resistance and improve patient outcomes.

Sorafenib increases NFE2L2 expression in cardiomyocytes, while ferroptosis inhibitors such as ferrostatin-1 (Fer-1) and deferoxamine (DFO) attenuate this effect, indicating that ferroptosis is involved in NFE2L2 activation. Taken together, these data suggest that NFE2L2 and its downstream pathways, including the HO-1/ferritin axis, may represent promising therapeutic targets for mitigating Sorafenib-induced cardiotoxicity. Further investigation of NFE2L2 agonists could enhance the safety of Sorafenib therapy.

Also, a positive correlation was observed between caspase 3 level and ATF6 level (r = 0.301, p = 0.030). In this study, markers associated with PERK and ATF6 signalling pathways were higher in CLL patients.

Enrichment analysis and protein expression profiling highlighted oligodendrocyte function and myelination as likely contributors to PSP pathogenesis. Our findings broaden the genetic landscape of PSP and suggest potential therapeutic avenues focused on modulating neuron-oligodendrocyte interactions.

Ebselen alleviated LPS-induced oxidative stress by modulating MDA and superoxide dismutase (SOD) levels in kidney tissues and SOD, glutathione peroxidase (GPx) and serum total antioxidant status (TAS) levels in serum. In conclusion, we report for the time that Ebselen might alleviate sepsis-induced AKI through the regulation of ER stress apoptosis and oxidative stress.

Targeting the ADSL-BECN1 axis by knock-in mutation or a cell-penetrating peptide inhibits autophagy and blunts liver tumor growth in mice. These findings broaden the physiological significance of ADSL in autophagy and liver tumor development.

Our results suggest the importance of UPR in the pathogenesis of extramedullary disease. UPR appears to be a promising avenue for further research.