CPEB4

Last update 08 May 2025

Basic Info

Synonyms

CPE-binding protein 4, CPE-BP4, CPEB4

+ [4]

Introduction

Sequence-specific RNA-binding protein that binds to the cytoplasmic polyadenylation element (CPE), an uridine-rich sequence element (consensus sequence 5'-UUUUUAU-3') within the mRNA 3'-UTR (PubMed:24990967). RNA binding results in a clear conformational change analogous to the Venus fly trap mechanism (PubMed:24990967). Regulates activation of unfolded protein response (UPR) in the process of adaptation to ER stress in liver, by maintaining translation of CPE-regulated mRNAs in conditions in which global protein synthesis is inhibited (By similarity). Required for cell cycle progression, specifically for cytokinesis and chromosomal segregation (PubMed:26398195). Plays a role as an oncogene promoting tumor growth and progression by positively regulating translation of t-plasminogen activator/PLAT (PubMed:22138752). Stimulates proliferation of melanocytes (PubMed:27857118). In contrast to CPEB1 and CPEB3, does not play role in synaptic plasticity, learning and memory (By similarity).

100 Clinical Results associated with CPEB4

100 Translational Medicine associated with CPEB4

0 Patents (Medical) associated with CPEB4

142

Literatures (Medical) associated with CPEB4

01 Mar 2025·JHEP Reports

CPEB4 modulates liver cancer progression by translationally regulating hepcidin expression and sensitivity to ferroptosis

Article

Author: Gallardo-Martínez, Carmen ; Ramírez-Pedraza, Marta ; Naranjo-Suarez, Salvador ; Delgado, M Eugenia ; Balvey, Alexandra ; Cárdenas, Beatriz I ; Martín, Judit ; Méndez, Raúl ; Belloc, Eulalia ; Boyle, Mark ; Fernandez, Mercedes

Background & AimsLiver cancer is a significant global health issue, with its incidence rising in parallel with the obesity epidemic. The limited therapeutic options available emphasize the need for a better understanding of the molecular pathways involved in its pathogenesis. While much of the previous research has focused on transcriptional changes, this study examines translational alterations, specifically the role of cytoplasmic polyadenylation element binding protein 4 (CPEB4), a key regulator of translation.MethodsWe analyzed publicly available patient databases and conducted studies using human and mouse liver cancer cells, xenograft and allograft models, mouse models of high-fat diet-related liver cancer, and CPEB4 knockout and knockdown mice and cell lines.ResultsPatient data analysis (n = 87) showed a strong correlation between low CPEB4 levels and reduced survival rates (p <0.001). In mouse models of diet-induced liver cancer (n = 10-15 per group), both systemic and hepatocyte-specific CPEB4 knockout mice exhibited significantly increased tumor burden compared with wild-type controls (p <0.05). In vitro studies using human and murine liver cancer cells (n = 3 biological replicates) demonstrated reduced sensitivity to ferroptosis upon CPEB4 depletion when induced by erastin or RSL3 (p <0.01). Mechanistically, CPEB4 deficiency suppressed hepcidin expression, leading to elevated ferroportin levels, decreased intracellular iron accumulation, and reduced lipid peroxidation (p <0.05).ConclusionsThis study uncovers a novel CPEB4-dependent mechanism linking translational control to liver cancer progression and ferroptosis regulation. Therapeutic strategies targeting CPEB4-mediated pathways hold promise for advancing treatment options in liver cancer.Impact and implicationsThis study addresses the pressing need for improved therapies in liver cancer, particularly given its increasing prevalence linked to obesity and metabolic-associated fatty liver disease. By uncovering the role of the RNA-binding protein cytoplasmic polyadenylation element binding protein 4 (CPEB4) in modulating iron regulation and cancer cell sensitivity to ferroptosis, our research highlights a new translational mechanism with potential therapeutic relevance. These findings are particularly significant for clinicians, researchers, and policymakers focused on advancing targeted treatments for hepatocellular carcinoma. If further validated in human clinical studies, targeting CPEB4-mediated pathways could help develop treatments that enhance cancer cell susceptibility to ferroptosis, offering a promising strategy for improving outcomes in patients with advanced liver cancer. Limitations of the study include the need for further clinical validation to confirm these preclinical findings in human disease contexts.

01 Mar 2025·Nature Nanotechnology

Measuring age-dependent viscoelasticity of organelles, cells and organisms with time-shared optical tweezer microrheology

Article

Author: Garcia-Cabau, Carla ; Krieg, Michael ; Sanfeliu-Cerdán, Neus ; Pezzano, Fabio ; Jiménez-Delgado, Senda ; Martínez-Fernández, Carmen ; Frigeri, Paolo-Antonio ; Ruprecht, Verena ; Català-Castro, Frederic ; Salvatella, Xavier ; Ortiz-Vásquez, Santiago ; Fernández-Campo, Martín

AbstractQuantifying the mechanical response of the biological milieu (such as the cell’s interior) and complex fluids (such as biomolecular condensates) would enable a better understanding of cellular differentiation and aging and accelerate drug discovery. Here we present time-shared optical tweezer microrheology to determine the frequency- and age-dependent viscoelastic properties of biological materials. Our approach involves splitting a single laser beam into two near-instantaneous time-shared optical traps to carry out simultaneous force and displacement measurements and quantify the mechanical properties ranging from millipascals to kilopascals across five decades of frequency. To create a practical and robust nanorheometer, we leverage both numerical and analytical models to analyse typical deviations from the ideal behaviour and offer solutions to account for these discrepancies. We demonstrate the versatility of the technique by measuring the liquid–solid phase transitions of MEC-2 stomatin and CPEB4 biomolecular condensates, and quantify the complex viscoelastic properties of intracellular compartments of zebrafish progenitor cells. In Caenorhabditis elegans, we uncover how mutations in the nuclear envelope proteins LMN-1 lamin A, EMR-1 emerin and LEM-2 LEMD2, which cause premature aging disorders in humans, soften the cytosol of intestinal cells during organismal age. We demonstrate that time-shared optical tweezer microrheology offers the rapid phenotyping of material properties inside cells and protein blends, which can be used for biomedical and drug-screening applications.

18 Feb 2025·International Journal of Medical Sciences

Molecular network analysis of CPEB4 translational control and targeting CPEB4/β-catenin to modulate invasion and migration of nasopharyngeal carcinoma cells

Article

Author: Tian, Chen ; Yingying, Wang ; Mingwan, Zhu ; Fen, Li ; Fuhai, Chen ; Zezhang, Tao ; Manli, Zeng ; Yuanyuan, Wei ; Yongping, Wang

Background: CPEB4, an RNA-binding protein that regulates the translational efficiency of target genes, has been implicated in playing dual roles in tumor progression across multiple cancer types. This study aims to investigate the role of CPEB4 in head and neck squamous cell carcinoma (HNSCC), particularly focusing on nasopharyngeal carcinoma. Methods: Differentially expressed proteins associated with CPEB4 were identified using iTRAQ-based proteomics. Consensus clustering stratified 495 HNSCC cases into two distinct molecular subtypes (C1 and C2). A prognostic risk model was constructed using LASSO regression. The effects of CPEB4 on cellular invasion and migration were analyzed in NPC cells. Western blotting assessed PI3K/AKT and WNT/β-catenin pathways and EMT markers. β-catenin nuclear activity was analyzed by immunofluorescence and western blot. A nude mouse xenograft model validated the CPEB4/β-catenin axis. Results: A total of 731 proteins were identified as differentially expressed. The C2 molecular subtype exhibited significantly worse prognosis, higher tumor stemness indices, and greater sensitivity to six commonly used chemotherapeutic agents compared to C1. Overexpression of CPEB4 in NPC cells enhanced invasion and migration. Mechanistically, CPEB4 upregulated β-catenin expression and nuclear activity by targeting CPE elements within the CTNNB1 mRNA, which were inhibited by β-catenin inhibitors. In vivo experiments confirmed that CPEB4 overexpression promoted tumor invasiveness and migration, effects that were effectively suppressed by β-catenin inhibitors. Conclusions: CPEB4 overexpression drives tumor progression in NPC by translationally upregulating β-catenin, thereby promoting cell invasion and migration. The poor prognosis associated with CPEB4 is linked to enhanced tumor aggressiveness. Importantly, β-catenin inhibitors effectively counteract the pro-invasive and pro-migratory effects mediated by CPEB4, underscoring their potential as therapeutic agents in CPEB4-overexpressing tumors.

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CPEB4

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