ETF1

Last update 08 May 2025

Basic Info

Synonyms

ERF, eRF1, ETF1

+ [7]

Introduction

Component of the eRF1-eRF3-GTP ternary complex, a ternary complex that mediates translation termination in response to the termination codons (PubMed:10676813, PubMed:16777602, PubMed:24486019, PubMed:26245381, PubMed:27863242, PubMed:36638793, PubMed:7990965). The eRF1-eRF3-GTP complex binds to a stop codon in the ribosomal A-site (PubMed:26245381, PubMed:27863242, PubMed:36638793). ETF1/ERF1 is responsible for stop codon recognition and inducing hydrolysis of peptidyl-tRNA (PubMed:26245381, PubMed:27863242, PubMed:36638793). Following GTP hydrolysis, eRF3 (GSPT1/ERF3A or GSPT2/ERF3B) dissociates, permitting ETF1/eRF1 to accommodate fully in the A-site and mediate hydrolysis of peptidyl-tRNA (PubMed:10676813, PubMed:16777602, PubMed:26245381, PubMed:27863242). Component of the transient SURF complex which recruits UPF1 to stalled ribosomes in the context of nonsense-mediated decay (NMD) of mRNAs containing premature stop codons (PubMed:19417104). Required for SHFL-mediated translation termination which inhibits programmed ribosomal frameshifting (-1PRF) of mRNA from viruses and cellular genes (PubMed:30682371).

100 Clinical Results associated with ETF1

100 Translational Medicine associated with ETF1

0 Patents (Medical) associated with ETF1

Literatures (Medical) associated with ETF1

01 May 2024·Nature Chemical Biology

Boric acid intercepts 80S ribosome migration from AUG-stop by stabilizing eRF1

Article

Author: Ito, Takuhiro ; Shirouzu, Mikako ; Saito, Hironori ; Yokoyama, Takeshi ; Tanaka, Mayuki ; Sotta, Naoyuki ; Tsuda, Kengo ; Shigematsu, Hideki ; Nishimoto, Madoka ; Iwasaki, Shintaro ; Fujiwara, Toru

In response to environmental changes, cells flexibly and rapidly alter gene expression through translational controls. In plants, the translation of NIP5;1, a boric acid diffusion facilitator, is downregulated in response to an excess amount of boric acid in the environment through upstream open reading frames (uORFs) that consist of only AUG and stop codons. However, the molecular details of how this minimum uORF controls translation of the downstream main ORF in a boric acid-dependent manner have remained unclear. Here, by combining ribosome profiling, translation complex profile sequencing, structural analysis with cryo-electron microscopy and biochemical assays, we show that the 80S ribosome assembled at AUG-stop migrates into the subsequent RNA segment, followed by downstream translation initiation, and that boric acid impedes this process by the stable confinement of eukaryotic release factor 1 on the 80S ribosome on AUG-stop. Our results provide molecular insight into translation regulation by a minimum and environment-responsive uORF.

01 Apr 2024·iScience

Eukaryotic release factor 1 from Euplotes promotes frameshifting at premature stop codons in human cells

Article

Author: Stefanov, Bozhidar-Adrian ; Nowacki, Mariusz ; Ajuh, Elvis ; Allen, Sarah

Human physiology is highly susceptible to frameshift mutations within coding regions, and many hereditary diseases and cancers are caused by such indels. Presently, therapeutic options to counteract them are limited and, in the case of direct genome editing, risky. Here, we show that release factor 1 (eRF1) from Euplotes, an aquatic protist known for frequent +1 frameshifts in its coding regions, can enhance +1 ribosomal frameshifting at slippery heptameric sequences in human cells without an apparent requirement for an mRNA secondary structure. We further show an increase in frameshifting rate at the premature termination sequence found in the HEXA gene of Tay-Sachs disease patients, or a breast cancer cell line that harbors a tumor-driving frameshift mutation in GATA3. Although the overall increase in frameshifting would need further improvement for clinical applications, our results underscore the potential of exogenous factors, such as Eu eRF1, to increase frameshifting in human cells.

02 Feb 2024·Medicine

BZW1 is a prognostic and immunological biomarker in pancreatic adenocarcinoma

Article

Author: Hu, Jia ; Xie, Mingjun ; Hu, Ke ; Qiao, Nan ; Luo, An ; Jiang, Yiping ; Xu, Henglang

Pancreatic adenocarcinoma is the most common malignant tumor of the digestive system and is called the “king of cancer” because it has been labeled with high malignancy, rapid progression, poor survival, and poor prognosis. Previously, it was reported that the basic leucine zipper and W2 domains 1 (BZW1) is involved in the progression of many tumors. However, its research in digestive system tumors such as pancreatic cancer is rarely studied. To explore potential biomarkers related to survival and prognosis of pancreatic cancer and provide a new targeted therapy for it. We first analyzed the mRNA and protein expression of BZW1 in pancreatic cancer. We then explored the correlation of BZW1 with survival prognosis and immune infiltration in pancreatic cancer patients. Finally, we explored BZW1-related gene enrichment analysis, including protein-protein interaction networks, gene ontology functional enrichment analysis, and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis. The mRNA and protein expression of the BZW1 gene in pancreatic cancer tissues were higher than those in adjacent normal tissues, and pancreatic cancer patients with high BZW1 expression had a poor prognosis. In addition, the expression of BZW1 was positively or negatively correlated with different immune cells of pancreatic cancer, such as CD4 + T lymphocytes, CD8 + T lymphocytes, B cells, macrophages, neutrophils, etc. Correlation enrichment analysis showed that we obtained 50 available experimentally determined BZW1-binding proteins and 100 targeted genes related to BZW1, and the intersection genes were eukaryotic translation termination factor 1 and Guanine nucleotide binding protein, alpha inhibiting activity polypeptide 3. Moreover, there was a positive correlation between BZW1 and eukaryotic translation termination factor 1 and Guanine nucleotide binding protein, alpha inhibiting activity polypeptide 3 genes in pancreatic cancer. Gene ontology enrichment analysis showed BZW1 was mainly related to biological processes such as “mRNA processing,” “RNA splicing,” “regulation of translational initiation,” and “activation of innate immune response.” The results of Kyoto Encyclopedia of Genes and Genomes pathway analysis further indicated that BZW1 may be involved in pancreatic carcinogenesis through the “spliceosome” and “ribosome.” The BZW1 gene may be a potential immunotherapy target and a promising prognostic marker for pancreatic cancer.

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ETF1

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