更新于：2024-05-01
eIF5A
真核细胞翻译起始因子5A
更新于：2024-05-01
基本信息
别名 eIF-4D、eIF-5A、eIF-5A-1 + [9] |
简介 Translation factor that promotes translation elongation and termination, particularly upon ribosome stalling at specific amino acid sequence contexts (PubMed:33547280). Binds between the exit (E) and peptidyl (P) site of the ribosome and promotes rescue of stalled ribosome: specifically required for efficient translation of polyproline-containing peptides as well as other motifs that stall the ribosome (By similarity). Acts as ribosome quality control (RQC) cofactor by joining the RQC complex to facilitate peptidyl transfer during CAT tailing step (By similarity). Also involved in actin dynamics and cell cycle progression, mRNA decay and probably in a pathway involved in stress response and maintenance of cell wall integrity (PubMed:16987817). With syntenin SDCBP, functions as a regulator of p53/TP53 and p53/TP53-dependent apoptosis (PubMed:15371445). Regulates also TNF-alpha-mediated apoptosis (PubMed:15452064, PubMed:17187778). Mediates effects of polyamines on neuronal process extension and survival (PubMed:17360499).
(Microbial infection) Cellular cofactor of human T-cell leukemia virus type I (HTLV-1) Rex protein and of human immunodeficiency virus type 1 (HIV-1) Rev protein, essential for mRNA export of retroviral transcripts. |
关联
靶点 |
作用机制 |
在研机构 |
原研机构 |
在研适应症 |
非在研适应症 |
最高研发阶段 |
首次获批国家/地区 |
首次获批日期 |
A Randomized, Open Labeled, Placebo Controlled, Two-Arm, Parallel Group, Multi-Centric, Oral Clinical Study To Evaluate The Sns-01/16 In Healthy Adult Human Female Volunteers Under Fasting Conditions.
Phase 1/2 Open-Label, Multiple-Dose, Dose-Escalation Study to Evaluate the Safety and Tolerability of SNS01-T Administered by Intravenous Infusion in Patients With Relapsed or Refractory B Cell Malignancies
100 项与 eIF5A 相关的临床结果
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100 项与 eIF5A 相关的转化医学
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2024-02-01International journal of molecular sciences
The Deficiency of Hypusinated eIF5A Decreases the Putrescine/Spermidine Ratio and Inhibits +1 Programmed Ribosomal Frameshifting during the Translation of Ty1 Retrotransposon in Saccharomyces cerevisiae.
Article
作者: Yu Xiao ; Ruanlin Wang ; Xiaxia Han ; Wei Wang ; Aihua Liang
Programmed ribosomal frameshifting (PRF) exists in all branches of life that regulate gene expression at the translational level. The eukaryotic translation initiation factor 5A (eIF5A) is a highly conserved protein essential in all eukaryotes. It is identified initially as an initiation factor and functions broadly in translation elongation and termination. The hypusination of eIF5A is specifically required for +1 PRF at the shifty site derived from the ornithine decarboxylase antizyme 1 (OAZ1) in Saccharomyces cerevisiae. However, whether the regulation of +1 PRF by yeast eIF5A is universal remains unknown. Here, we found that Sc-eIF5A depletion decreased the putrescine/spermidine ratio. The re-introduction of Sc-eIF5A in yeast eIF5A mutants recovered the putrescine/spermidine ratio. In addition, the Sc-eIF5A depletion decreases +1 PRF during the decoding of Ty1 retrotransposon mRNA, but has no effect on -1 PRF during the decoding of L-A virus mRNA. The re-introduction of Sc-eIF5A in yeast eIF5A mutants restored the +1 PRF rate of Ty1. The inhibition of the hypusine modification of yeast eIF5A by GC7 treatment or by mutating the hypusination site Lys to Arg caused decreases of +1 PRF rates in the Ty1 retrotransposon. Furthermore, mutational studies of the Ty1 frameshifting element support a model where the efficient removal of ribosomal subunits at the first Ty1 frame 0 stop codon is required for the frameshifting of trailing ribosomes. This dependency is likely due to the unique position of the frame 0 stop codon distance from the slippery sequence of Ty1. The results showed that eIF5A is a trans-regulator of +1 PRF for Ty1 retrotransposon and could function universally in yeast.
2024-01-23American journal of respiratory and critical care medicine
Hypusine Signaling Promotes Pulmonary Vascular Remodeling in Pulmonary Arterial Hypertension.
Article
作者: Sarah-Eve Lemay ; Yann Grobs ; Charlotte Romanet ; Sandra Martineau ; Mabrouka Salem ; Tsukasa Shimauchi ; Sandra Breuils-Bonnet ; Alice Bourgeois ; Charlie Théberge ; Andréanne Pelletier ; François Potus ; Steeve Provencher ; Sébastien Bonnet ; Olivier Boucherat
RATIONALE:
The ubiquitous polyamine spermidine is essential for cell survival and proliferation. One important function of spermidine is to serve as a substrate for hypusination, a post-translational modification process that occurs exclusively on eukaryotic translation factor 5A (eIF5A) and ensures efficient translation of various gene products. Pulmonary arterial hypertension (PAH) is a life-threatening disease characterized by progressive obliteration of the small pulmonary arteries (PAs) due to excessive proliferation of PA smooth muscle cells (PASMCs) and suppressed apoptosis.
OBJECTIVES:
To characterize the role of hypusine signaling in PAH.
METHODS:
Molecular, genetic, and pharmacological approaches were used both in vitro and in vivo to investigate the role of hypusine signaling in pulmonary vascular remodeling.
MEASUREMENTS AND MAIN RESULTS:
Hypusine forming enzymes (deoxyhypusine synthase, DHPS and deoxyhypusine hydroxylase, DOHH) and hypusinated eIF5A are overexpressed in distal PAs and isolated PASMCs from PAH patients and animal models. In vitro, inhibition of DHPS using GC7 or short hairpin RNA resulted in a decrease in PAH-PASMC resistance to apoptosis and proliferation. In vivo, inactivation of one allele of Dhps targeted to smooth muscle cells alleviates PAH in mice and that its pharmacological inhibition significantly decreases pulmonary vascular remodeling and improves hemodynamics and cardiac function in two rat models of established PAH. Using mass spectrometry, we show that hypusine signaling promotes the expression of a broad array of proteins involved in oxidative phosphorylation, thus supporting the bioenergetic requirements of cell survival and proliferation.
CONCLUSIONS:
These findings support inhibiting hypusine signaling as a potential treatment for PAH.
2024-01-21Genes
Selection and Validation of Reference Genes for Gene Expression Studies in Euonymus japonicus Based on RNA Sequencing.
Article
作者: Wei Guo ; Yihui Yang ; Bo Ma ; Wenbo Wang ; Zenghui Hu ; Pingsheng Leng
Euonymus japonicus is one of the most low-temperature-tolerant evergreen broad-leaved tree species in the world and is widely used in urban greening. However, there are very few molecular biology studies on its low-temperature tolerance mechanism. So far, no researcher has selected and reported on its reference genes. In this study, 21 candidate reference genes (12 traditional housekeeping genes and 9 other genes) were initially selected based on gene expression and coefficient of variation (CV) through RNA-Seq (unpublished data), and qRT-PCR was used to detect the expression levels of candidate reference genes in three different groups of samples (leaves under different temperature stresses, leaves of plants at different growth stages, and different organs). After further evaluating the expression stability of these genes using geNorm, NormFinder, Bestkeeper, and RefFind, the results show that the traditional housekeeping gene eIF5A and the new reference gene RTNLB1 have good stability in the three different groups of samples, so they are reference genes with universality. In addition, we used eIF5A and RTNLB1 as reference genes to calibrate the expression pattern of the target gene EjMAH1, which confirmed this view. This article is the first to select and report on the reference gene of E. japonicus, laying the foundation for its low-temperature tolerance mechanism and other molecular biology research.
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