预约演示

更新于：2025-05-07

EF-1A

更新于：2025-05-07

基本信息

别名

DKFZp434g247、EF-1a、eRF3c

+ [7]

简介

GTPase component of the Pelota-HBS1L complex, a complex that recognizes stalled ribosomes and triggers the No-Go Decay (NGD) pathway (PubMed:21448132, PubMed:23667253, PubMed:27863242). The Pelota-HBS1L complex recognizes ribosomes stalled at the 3' end of an mRNA and engages stalled ribosomes by destabilizing mRNA in the mRNA channel (PubMed:27863242). Following mRNA extraction from stalled ribosomes by the SKI complex, the Pelota-HBS1L complex promotes recruitment of ABCE1, which drives the disassembly of stalled ribosomes, followed by degradation of damaged mRNAs as part of the NGD pathway (PubMed:21448132, PubMed:32006463).

关联

项与 EF-1A 相关的药物

FFT-135

靶点

EF-1A x GSPT1 x GSPT2

作用机制

EF-1A降解剂 [+2]

在研机构

F5 Therapeutics, Inc.

原研机构

F5 Therapeutics, Inc.

在研适应症

结直肠癌 [+2]

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

HBS1L/PELO Complex(Tango)

靶点

EF-1A x PELO

作用机制

EF-1A modulators [+1]

在研机构

Tango Therapeutics, Inc.

原研机构

Tango Therapeutics, Inc.

在研适应症

肿瘤

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 EF-1A 相关的临床结果

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100 项与 EF-1A 相关的转化医学

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0 项与 EF-1A 相关的专利（医药）

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633

项与 EF-1A 相关的文献（医药）

2025-07-01·Microbiological Research

Bacillus velezensis HR6-1 enhances salt tolerance in tomato by increasing endogenous cytokinin content and improving ROS scavenging

Article

作者: Dong, Han ; Shang, Wenkai ; Dong, Xiaoxing ; Ma, Xiaojing ; Piao, Fengzhi ; Guo, Zhixin ; Ouyang, Zhaopeng ; Ma, Haohao ; Li, Xinzheng ; Wang, Yong ; Zhu, Mengmeng ; Luo, Hengbin ; Shen, Shunshan ; Zhang, Tao

The application of plant growth-promoting rhizobacteria (PGRP) is a promising and innovative strategy for alleviating salt stress in plants. However, the mechanism underlying PGRP-mediated alleviation of salt stress is currently unclear. In this study, we observed that the tomatoes inoculated with Bacillus velezensis HR6-1 exhibited better growth indicators and photosynthesis-related parameters than non-colonized tomatoes under salt stress. Physiological analysis showed that tomatoes inoculated with HR6-1 exhibited better Na⁺/K⁺ balance and lower ROS accumulation and oxidative damage, and higher activities of antioxidant enzymes compared with non-colonized tomatoes under salt stress. Transcriptome analysis revealed that under salt stress, HR6-1 treatment improved the expression of various transcription factors (especially WRKYs and ERFs) and many genes related to plant hormone signal transduction, the MAPK signaling pathway, the salt overly sensitive pathway, and detoxification in tomatoes. Moreover, HR6-1 inoculation increased the content of cZ- and tZ-type cytokinins in salt-treated tomato seedlings, which was consistent with the high expression of several cytokinin synthesis genes. Treatment with a cytokinin synthesis inhibitor prevented HR6-1-mediated improvement in salt tolerance in tomato seedlings, implying that HR6-1 stimulates cytokinin synthesis to enhance tomato resistance to salt stress. Our findings identify a potential biostimulant for improving tomato growth under salt stress and deepen our understanding of PGPR-mediated salinity alleviation in tomato seedlings.

2025-06-01·Molecular Therapy Methods & Clinical Development

Targeted spiral ganglion neuron degeneration in parvalbumin-Cre neonatal mice

Article

作者: Shibata, Seiji B ; Cutri, Raffaello M ; Lin, Joshua S ; Nguyen, Nhi V ; Parikh, Miti J

The spiral ganglion neurons (SGNs) are the primary afferent neurons in the cochlea; damage to the SGNs leads to irreversible hearing impairment. Mouse models that allow selective SGN degeneration while sparing other cell types in the cochlea are lacking. Here, we investigated a genetic ablation method of the SGN using a Cre-responsive adeno-associated virus (AAV) vector expressing diphtheria toxin subunit-A (DTA). We microinjected AAV2-retro-FLEX-DTA-mCherry driven by the EF1a or hSYN promoter in neonatal parvalbumin-Cre (PV^Cre) and wild-type strains via the posterior semicircular canal. Apoptotic markers were observed in the degenerating SGNs as early as 3 days. After 1 week, we assessed the SGN cell density, revealing an average degeneration of 60% for AAV-DTA driven by the EF1a promoter and 61% for that driven by the hSYN promoter. By 1 month, injected ears demonstrated a nearly complete loss of SGN, while hair cell morphology was intact. The auditory brain stem response result showed significantly elevated threshold shifts at 1 month, while the distortion-product otoacoustic emissions function remained intact. Furthermore, we show that our method did not effectively ablate SGN in adult PV^Cre mice. We generated a neonatal mouse model with primary SGN degeneration in PV^Cre mice, mimicking auditory neuropathy phenotype using an AAV Cre-dependent expression of DTA.

2025-04-01·Plant Physiology and Biochemistry

Molecular insights into DaERF108-mediated regulation on asperosaponin VI biosynthesis under cold tolerance in Dipsacus asper

Article

作者: Xu, Jiao ; Zhou, Guang ; Xiao, Chenghong ; Xu, Chunyun ; Zhou, Tao ; Yang, Huanhuan

Plants frequently modulate their hormonal signaling pathways in response to stress, thereby regulating the synthesis of secondary metabolites and adapting to fluctuations in their surroundings. The APETALA2/ethylene-responsive factor (AP2/ERF) domain transcription factors are important in regulating abiotic stress tolerance. The accumulation of asperosaponin VI in the root was significantly enhanced under low temperature stress, which exhibited a correlation with the AP2/ERF family. However, the involvement of AP2/ERF in regulating asperosaponin VI biosynthesis under cold stress remains ambiguous. Under cold stress conditions below 10 °C, we observed the accumulation of asperosaponin VI and an increase in jasmonic acid (JA) levels. This response was attributed to the activation of the JA synthesis pathway induced by low temperatures. Additionally, a comprehensive analysis of the full-length transcriptome of Dipsacus asper identified a total of 80 DaAP2/ERF transcription factors, which exhibited significant homology with Arabidopsis thaliana and Citrus ERFs based on phylogenetic analysis. Furthermore, qRT-PCR analysis demonstrated that both cold stress and methyl jasmonate (MeJA) induction upregulated DaERF108 expression. The expression of DaERF108 is notably upregulated in the leaves and during the early stages of growth and development of D. asper, while subcellular localization analysis confirmed its presence in the nucleus. The overexpression of DaERF108 significantly enhanced the accumulation of oleanolic acid, a precursor of asperosaponin VI, and activated the triterpenoid biosynthesis pathway in Arabidopsis roots. Additionally, the overexpression of DaERF108 induced the activation of the terpenoid synthesis pathway under cold stress conditions. Notably, there was a positive correlation between DaERF108 expression and genes involved in asperosaponin VI biosynthesis, particularly with 3-hydroxy-3-methylglutaryl coenzyme A synthase (DaHMGS). The interaction between DaERF108 and the GCC-box element in the DaHMGS promoter was demonstrated by LUC and Y1H assays, leading to enhanced activity. These findings suggest that DaERF108 specifically binds to the G-box element, thereby regulating DaHMGS gene expression, activating the JA signaling pathway, and promoting asperosaponin VI biosynthesis in response to cold stress.

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