{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Eukaryotic translation initiation factor 3 subunit H (EIF3H) is a component of the multi‐subunit eIF3 complex that facilitates translation initiation. Although not one of the evolutionarily conserved core subunits, EIF3H associates with other non‐conserved factors to form a functional core that supports efficient assembly of the translation preinitiation complex."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " Increasing evidence indicates that dysregulated expression or amplification of EIF3H contributes to oncogenesis by stimulating protein synthesis and promoting malignant traits. Elevated levels or copy number gains of EIF3H have been correlated with enhanced tumor growth, invasiveness, and metastasis in colorectal, hepatocellular, and non‐small cell lung cancers."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "2", "end_ref": "5"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition to its well‐established role in translation initiation, EIF3H has emerged with noncanonical functions that link it to post‐translational regulation. In esophageal squamous cell carcinoma models, for instance, EIF3H directly interacts with and deubiquitinates the transcription factor Snail, thereby stabilizing it and promoting epithelial–mesenchymal transition."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " Similarly, a separate study uncovered that EIF3H can deubiquitinate YAP—a key effector of the Hippo pathway—via a unique catalytic triad (Asp90, Asp91, and Gln121), ultimately enhancing YAP stability and driving tumor invasion and metastasis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n The proper folding and integration of EIF3H into the eIF3 complex is also critical for its function and is promoted by the cytosolic chaperonin CCT, which assists in the maturation of several eIF3 subunits."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " Moreover, unbiased genetic screens have identified EIF3H in contexts related to transgene silencing, suggesting that beyond its translational and deubiquitinase roles, EIF3H might partake in additional layers of gene expression or epigenetic regulation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " Finally, interactions with other regulatory proteins such as TRC8 imply that EIF3H may integrate signals from metabolic pathways with translational control."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these findings highlight a dual role for EIF3H: it not only contributes to the canonical process of translation initiation but also acts as a deubiquitinating enzyme that modulates the stability of oncogenic regulators. This multifunctional nature of EIF3H underlies its contribution to cancer cell proliferation, invasion, and metastasis, making it a promising prognostic marker and potential therapeutic target in various malignancies.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Mamiko Masutani, Nahum Sonenberg, Shigeyuki Yokoyama, et al. 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