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Results for “RPL4”

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PubMed2025

CCT8 drives colorectal cancer progression via the RPL4-MDM2-p53 axis and immune modulation.

PURPOSE: Colorectal cancer (CRC) ranks high in global mortality, emphasizing the need for effective interventions. The aim of the research is to elucidate the oncogenic role of CCT8 in CRC and its interaction with RPL4 in the RPL4-MDM2-p53 axis. METHODS: TIMER 2.0, TCGA, and GTEx databases were used to analyze CCT8 expression patterns in CRC. Immunohistochemistry was performed to examine CCT8 distribution in CRC tissues and adjacent non-tumor tissues. Functional assays, including CCK-8, transwell, wound-healing, and flow cytometry, were conducted using DLD-1 and HCT116 cell lines to assess the effects of CCT8 on cell proliferation, migration, invasion, and apoptosis. Gene set enrichment analysis, protein-protein interaction network analysis, and co-immunoprecipitation were performed to explore the interaction between CCT8 and RPL4 and their role in the RPL4-MDM2-p53 pathway. Additionally, gene set variation analysis was applied to investigate the relationship between CCT8/RPL4 expression and immune infiltration patterns in CRC. RESULTS: CCT8 was significantly upregulated in CRC and associated with tumor progression. Mechanistically, CCT8 potentially synergizes with RPL4 concluded from their positive correlation and similar immune infiltration patterns, influencing the RPL4-MDM2-p53 axis and contributing to p53 ubiquitination and degradation. CONCLUSION: These findings underscore the oncogenic significance of CCT8 in CRC and shed light on its molecular mechanisms, paving the way for potential therapeutic applications.

Humans↗

PubMed1992

Inhibitory neuron produces heterosynaptic inhibition of the sensory-to-motor neuron synapse in Aplysia.

We have identified an inhibitory neuron (RPL4) in the right pleural ganglion of Aplysia, which produced hyperpolarization of the sensory and motor neurons involved in the tail withdrawal reflex. Activation of RPL4 significantly reduced the amplitude of excitatory postsynaptic potentials produced in tail motor neurons by action potentials triggered in sensory neurons. This example of heterosynaptic inhibition was due, at least in part, to an increase in membrane input conductance in the motor neuron. Since the synaptic strength of the sensory-to-motor neuron connection has been associated with the strength of the tail withdrawal reflex, RPL4 may contribute to modulation of that reflex.

Action Potentials↗

PubMed2026

Activation of mTOR pathway by human cytomegalovirus promoting host ribosomal protein expression by coordinated transcriptional and translational controls.

Human cytomegalovirus (HCMV) profoundly reprograms host transcription and RNA metabolism, yet its impact on transcription start site (TSS) regulation of host genes remains poorly understood. Here, we employed NanoCap Analysis of Gene Expression sequencing (NanoCAGE-seq) to investigate HCMV-driven changes in alternative TSS usage across the host transcriptome. We identified widespread TSS switching, with ribosomal protein genes (RPGs) emerging as a highly enriched category. Alternative TSS usage produced isoforms with distinct 5'untranslated regions (UTRs), thereby altering cis-regulatory elements that shape translational efficiency. Integrative transcriptomic and proteomic analyses revealed a paradoxical accumulation of RPG proteins despite transcriptional downregulation during infection. Using 5' Rapid Amplification of cDNA Ends (5'RACE), we characterized four RPGs of RPL4, RPS11, RPS23, and RPS24 that generated 5'UTR variants through alternative TSS usage. Notably, isoforms containing a 5'terminal oligopyrimidine (5'TOP) motif were significantly enriched, correlating with mTOR activation induced by HCMV. Functional assays with bicistronic reporter constructs in HEK293 cells and infection models in human embryonic lung fibroblasts demonstrated that the RPL4 5'TOP isoform exhibited enhanced mTORC1-driven translation compared with non-5'TOP counterparts. Importantly, RPL4 upregulation facilitated viral protein synthesis and boosted production of infectious virions. Together, our findings reveal that dynamic TSS switching of RPGs provides a simple, yet effective, mechanism for fine-tuning mTORC1-responsive translation. By co-opting host transcriptional and translational programs, HCMV enhances ribosome function to optimize the cellular environment for productive viral replication.

Humans↗

PubMed2025

Hepatocyte proteome destabilization and novel targets for PFASs unveiled through combined thermal proteome profiling and deep transfer learning.

Identifying protein targets for per- and polyfluoroalkyl substances (PFASs) is essential to understand their toxicity and health risks. However, knowledge about their interacting proteins is limited since reliable identification methods are lacking. We developed an integrated approach combining thermal proteome profiling (TPP) and deep transfer learning (DTL) modeling to efficiently identify cellular targets of PFAS. TPP measured PFAS binding proteins and the affinities by nanospray liquid chromatography tandem mass spectrometry, while DTL models were constructed to predict PFAS-protein affinities using neural network algorithms. TPP results revealed that PFASs uniquely destabilized the proteome of HepG2 cells, unlike the stabilizing effects by other xenobiotics. Key protein targets for three representative PFASs (PFOA, GenX and Novec 649) were identified, which exhibited weak binding affinities (median EC50 ≈ 30 μM). The number of protein targets increased with molecular weights among the three PFASs. The DTL model achieved a higher Pearson correlation coefficient of 0.89, and reduced mean squared errors by 54 % over previous models for drug-protein interactions. Notably, TPP and DTL jointly pinpointed ribosomal proteins as novel targets of GenX, potentially linking it to cell apoptosis through disrupted protein synthesis. Biolayer interferometry validated GenX binding to RPL4 protein, driven by electrostatic interactions and halogen bonds. This integrated approach effectively uncovers novel PFASs targets, advancing insights into their adverse health effects.

Humans↗

PubMed2026

Comparative toxicoproteomics reveals distinct proteostasis and ribosomal stress signatures of CMIT and PHMG.

Methylchloroisothiazolinone (CMIT) and polyhexamethylene guanidine (PHMG) are antimicrobial biocides associated with pulmonary toxicity, although their comparative cellular stress mechanisms remain unclear. Here, we investigated how CMIT and PHMG differentially alter the proteome of human alveolar epithelial A549 cells under subcytotoxic conditions. Cells were exposed to CMIT or PHMG, and global proteomic profiling was performed using label-free liquid chromatography-tandem mass spectrometry. Differentially expressed proteins (DEPs) were identified at a 1% false discovery rate with an absolute log2 fold change ≥1. Functional analyses were conducted using Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and Ingenuity Pathway Analysis, and selected proteins were validated by western blotting. Comparative toxicoproteomics revealed distinct stress-response signatures induced by the two biocides. CMIT preferentially altered proteins associated with proteostasis, oxidative stress, and protein quality control, whereas PHMG was characterized by coordinated depletion of ribosome-associated and translation-related proteins. A total of 73 and 155 DEPs were identified in CMIT- and PHMG-treated cells, respectively, with 22 proteins shared between treatments. Western blotting confirmed PSMD3, TUBB2A, and GLRX1 as CMIT-responsive proteins and THRAP3, DHX15, and RPL4 as PHMG-responsive markers. These findings provide comparative mechanistic insight into how CMIT and PHMG induce distinct epithelial stress responses and identify candidate protein markers that may support future in vitro assessment of biocide-induced pulmonary toxicity.

CMIT↗