{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Recent studies have revealed multiple roles for the cytoplasmic polyadenylation element‐binding protein 3 (CPEB3) in controlling mRNA translation under both normal and disease conditions. In the nervous system, CPEB3 acts as a sequence‐specific RNA‐binding protein that modulates local synthesis of proteins important for synaptic structure and plasticity. In its basal state, CPEB3 functions largely as a translational repressor by binding target mRNAs—including those encoding AMPA receptor subunits and other plasticity‐related proteins—to confine synaptic strength and limit protein synthesis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "5"}]}, {"type": "t", "text": " Yet, upon neuronal stimulation—for example, via NMDA receptor activation—CPEB3 is subject to several post‐translational modifications such as deSUMOylation, calpain‐mediated proteolysis, and Neuralized1‐dependent ubiquitination. These modifications trigger a conformational switch wherein CPEB3 adopts a prion‐like aggregated state, relieving its repressive effect and switching its activity to promote the local translation of specific mRNAs required for dendritic spine growth and the consolidation of long‐term memory."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "8"}, {"type": "fg_fs", "start_ref": "3", "end_ref": "5"}]}, {"type": "t", "text": " In addition, CPEB3 can associate with regulatory cofactors (for example, Tob, which recruits the Caf1 deadenylase) to coordinate the timing of mRNA deadenylation and decay."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond its roles in the central nervous system, CPEB3 also appears to act as a tumor suppressor in several cancers. In colorectal, hepatocellular, and gastric cancers, reduced CPEB3 expression is correlated with enhanced oncogenic signaling through pathways such as IL‐6R/STAT3 and EGFR, which in turn affect cell proliferation, migration, and metastasis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "10", "end_ref": "14"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n A further intriguing aspect of CPEB3 biology is the discovery of a self‐cleaving ribozyme nested within an intron of the CPEB3 gene. This ribozyme, evolutionarily conserved among mammals, may contribute to an autoregulatory mechanism that governs CPEB3 expression and activity, although its full functional significance remains under investigation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "15", "end_ref": "17"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these findings underscore the multifaceted roles of CPEB3 as a central regulator of mRNA translation. By dictating the local synthesis of key synaptic proteins and by restraining aberrant oncogenic signaling through its tumor‐suppressive functions, CPEB3 emerges as a critical mediator of both neural plasticity and cellular homeostasis.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Yi-Shuian Huang, Ming-Chung Kan, Chien-Ling Lin, et al. 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