EIF4H (Eukaryotic Translation Initiation Factor 4H)

This study demonstrates the feasibility of using allele-specific proteomics at the endogenous protein levels by exploiting heterozygous coding variants. Overall, our approach extends the toolbox available to investigate allele-specific differences in mRNA translation potential, a relatively underexplored layer of gene expression regulation that could reveal inter-individual differences in disease-relevant phenotypes.

Collectively, our findings reveal that KRT14 contributes to chemoresistance in BLCA not only via its structural roles but also by directly regulating translational machinery through eIF4H, leading to upregulation of the metabolic enzyme ACOX2. The newly defined KRT14-eIF4H-ACOX2 axis orchestrates lipid metabolic reprogramming and cell survival, underscoring the KRT14-eIF4H interface as a promising therapeutic target for overcoming cisplatin resistance in BLCA.

We have identified novel HKGs useful in breast cancer research and proved that they exhibit more stable expression compared to previously known HKGs. These findings may offer researchers and clinicians a more reliable normalization standard for gene expression analysis, potentially enhancing the accuracy of breast cancer diagnosis and the selection of personalized treatments.

We identify a gene signature (KRT19, RUNX3, and SCRT2) and a protein signature (ATXN10, EIF4H, ITGAV, and NCAM1) associated with an increased risk of early recurrence. Furthermore, we integrated these markers with imaging-derived features, obtaining a better stratification of IDH-mutant glioma patients in comparison to histomolecular classification alone.

In this issue of Developmental Cell, Kim et al. identify that altered autophagy and SFPQ-dependent EIF4H splicing during senescence redirects translation to promote inflammation, informing therapeutic strategies for cancer and other age-related diseases.

This proposes that the underlying molecular mechanisms governing ATLL and ALL may largely overlap concerning these cellular processes. However, considerable increased expression of RAB3GAP2 was observed in ATLL compared to ALL.

These autophagy-centric inflammatory controls appear to be conserved during human tissue aging and cancer. Our work highlights the role of autophagy in the on-demand functional remodeling of cellular proteomes as well as the crosstalk between autophagy, alternative splicing, and inflammatory translation.

Drug sensitivity analysis demonstrated lower IC50 for AZD6244 and PD.0332991 in high-risk groups and lower IC50 for cisplatin, ATRA, QS11, and vinorelbine in the low-risk group. Furthermore, the differential expression of GRTTK-related signatures including CDK2, TCEA1, and TMEM209 were verified in ESCC tissues and paracancerous tissues. Overall, the novel GRTTK-based prognostic model can serve as indicators to predict the survival status and immunotherapy response of patients with ESCC, thereby providing guidance for the development of personalized treatment strategies.

After B cell activation in vitro, EIF4A1 facilitates an increased rate of protein synthesis, MYC expression, and expression of cell cycle regulators. However, EIF4A1-deficient cells remain viable, whereas inhibition of EIF4A1 and EIF4A2 by Hippuristanol treatment induces cell death.

Based on the results from the present study, we hypothesize that the dysregulation of EIF4A1 might be involved in the pathophysiology of LUAD development by promoting cancer growth and changing the tumor immune microenvironment. This can be used to develop potential diagnostic biomarkers or therapeutic targets for LUAD.