EIF2B4 (Eukaryotic Translation Initiation Factor 2B Subunit Delta)

However, the downstream effectors and mechanistic pathways linking translation control to tumorigenesis remain incompletely defined. This review summarizes current biochemical understanding of 5MP1 in translation initiation and synthesizes evidence supporting its tumor-promoting activities, outlining key questions and future directions.

Recent advances reveal that, beyond cis-regulatory uORFs, trans-acting factors such as translation initiation factors and associated RNA-binding proteins critically influence ATF4 translation. Understanding these mechanisms provides insight into ISR plasticity and its implications for development, aging, and disease.

Treatment with small molecule eIF2B activators 2BAct and ISRIB increases oligodendrocyte survival, CNS myelination, and doubled the Jimpy lifespan. These results suggest that ISR modulation could provide therapeutic benefit to PMD patients.

EIF2B4 functions as a previously unrecognized translational regulator that promotes HCC progression and immune evasion by enhancing STAT3 translation through a GEF-dependent mechanism. These findings highlight EIF2B4 as a potential therapeutic target and biomarker to improve immunotherapy responsiveness in HCC.

In contrast, a nonactivating GCN2-targeting agent does not affect viability. These results provide a clearer understanding of the challenges and opportunities for the clinical development of compounds targeting GCN2.

In contrast, a nonactivating GCN2-targeting agent does not impact viability. These results provide a clearer understanding of the challenges and opportunities for the clinical development of compounds targeting GCN2.

In addition, knockdown of TOMM40L significantly inhibited cell progression and stemness. The newly constructed SRS model is a potential biomarker for assessing HCC prognosis, and the key gene TOMM40L exhibits oncogenic properties.

Notably, astrocytes harboring a vanishing white matter-associated EIF2B5 mutation revealed that translational attenuation alone is insufficient to amplify cytokine-induced gene expression. Together, these findings identify a PERK/eIF2α/JAK1 signaling axis that sensitizes astrocytes to inflammatory cytokines, providing new mechanistic insights into the interactions between ER stress and neuroinflammation.

Moreover, ISR activation decreased cholesterol biosynthesis, a process critical for myelin formation and maintenance. As such, persistent ISR engagement may contribute to pathology in other demyelinating diseases.

To prevent incorrect selection of a reference gene in dormant tumor cells, we analyzed the expression stability of the widely used housekeeping genes GAPDH, ACTB, TUBA1A, RPS23, RPS18, RPL13A, PGK1, EIF2B1, TBP, CYC1, B2M, and YWHAZ in the T98G, A549, and PA-1 cancer cell lines treated with the dual mTOR inhibitor AZD8055...The optimal reference genes among the 12 candidate reference genes were not revealed in the PA-1 cell line. Validation of the stability of the 12 investigated genes demonstrated that the incorrect selection of a reference gene resulted in a significant distortion of the gene expression profile in dormant cancer cells.

Oligodendrocytes are the major contributors to the development of ataxia, but astrocyte-specific Eif2b5 conditional mice display several histological and molecular key features of VWM. In conclusion, the view of a single cell population being responsible for the onset and development of VWM needs to be replaced by the concept of VWM as a disease involving diverse cell types.

Our study established a rapid myelinating oligodendrocyte brain model in VWM for the first time, providing a more effective and tractable platform for further study of this condition and other white matter diseases. Furthermore, our findings suggested that ISRIB may have potential as a clinical treatment for VWM.