Search results for "5a"

eIF5A facilitates translation termination globally and promotes the elongation of many non polyproline-specific tripeptide sequences

2017

Abstract eIF5A is an essential protein involved in protein synthesis, cell proliferation and animal development. High eIF5A expression is observed in many tumor types and has been linked to cancer metastasis. Recent studies have shown that eIF5A facilitates the translation elongation of stretches of consecutive prolines. Activated eIF5A binds to the empty E-site of stalled ribosomes, where it is thought to interact with the peptidyl-tRNA situated at the P-site. Here, we report a genome-wide analysis of ribosome stalling in Saccharomyces cerevisiae eIF5A depleted cells using 5Pseq. We confirm that, in the absence of eIF5A, ribosomes stall at proline stretches, and extend previous studies by …

C3 Drives Inflammatory Skin Carcinogenesis Independently of C5

2021

Nonmelanoma skin cancer such as cutaneous squamous cell carcinoma (cSCC) is the most common form of cancer and can occur as a consequence of DNA damage to the epithelium by UVR or chemical carcinogens. There is growing evidence that the complement system is involved in cancer immune surveillance; however, its role in cSCC remains unclear. Here, we show that complement genes are expressed in tissue from patients with cSCC, and C3 activation fragments are present in cSCC biopsies, indicating complement activation. Using a range of complement-deficient mice in a two-stage mouse model of chemically-induced cSCC, where a subclinical dose of 7,12-dimethylbenz[a]anthracene causes oncogenic mutatio…

Comprehensive Screening for Naturally Occurring Hepatitis C Virus Resistance to Direct-Acting Antivirals in the NS3, NS5A, and NS5B Genes in Worldwid…

2015

ABSTRACTThere is no comprehensive study available on the natural hepatitis C virus (HCV) polymorphism in sites associated with resistance including all viral genotypes which may present variable susceptibilities to particular direct-acting antivirals (DAAs). This study aimed to analyze the frequencies, genetic barriers, and evolutionary histories of naturally occurring resistance-associated variants (RAVs) in the six main HCV genotypes. A comprehensive analysis of up to 103 RAVs was performed in 2,901, 2,216, and 1,344 HCV isolates for the NS3, NS5A, and NS5B genes, respectively. We report significant intergenotypic differences in the frequencies of natural RAVs for these three HCV genes. I…

The Monoclonal Antitoxin Antibodies (Actoxumab–Bezlotoxumab) Treatment Facilitates Normalization of the Gut Microbiota of Mice with Clostridium diffi…

2016

Antibiotics have significant and long-lasting impacts on the intestinal microbiota and consequently reduce colonization resistance against Clostridium difficile infection (CDI). Standard therapy using antibiotics is associated with a high rate of disease recurrence, highlighting the need for novel treatment strategies that target toxins, the major virulence factors, rather than the organism itself. Human monoclonal antibodies MK-3415A (actoxumab–bezlotoxumab) to C. difficile toxin A and toxin B, as an emerging non-antibiotic approach, significantly reduced the recurrence of CDI in animal models and human clinical trials. Although the main mechanism of protection is through direct neutraliza…

Frequent NS5A and multiclass resistance in almost all HCV genotypes at DAA failures: What are the chances for second-line regimens?

2017

CCDC 838880: Experimental Crystal Structure Determination

2012

Related Article: J.Barjau, J.Fleischhauer, G.Schnakenburg, S.R.Waldvogel|2011|Chem.-Eur.J.|17|14785|doi:10.1002/chem.201102722

Biochemical quantitation of the eIF5A hypusination in Arabidopsis thaliana uncovers ABA-dependent regulation.

2014

The eukaryotic translation elongation factor eIF5A is the only protein known to contain the unusual amino acid hypusine which is essential for its biological activity. This post-translational modification is achieved by the sequential action of the enzymes deoxyhypusine synthase (DHS) and deoxyhypusine hydroxylase (DOHH). The crucial molecular function of eIF5A during translation has been recently elucidated in yeast and it is expected to be fully conserved in every eukaryotic cell, however the functional description of this pathway in plants is still sparse. The genetic approaches with transgenic plants for either eIF5A overexpression or antisense have revealed some activities related to t…

CCDC 2067944: Experimental Crystal Structure Determination

2022

Related Article: Jingyu Zhang, Wei Xia, Saskia Huda, Jas S. Ward, Kari Rissanen, Markus Albrecht|2021|Adv.Synth.Catal.|363|3121|doi:10.1002/adsc.202100290

CCDC 2169529: Experimental Crystal Structure Determination

2023

Related Article: Renè Hommelsheim, Sandra Bausch, Arjuna Selvakumar, Mostafa Amer, Khai-Nghi Truong, Kari Rissanen, Carsten Bolm|2023|Chem.-Eur.J.|29|e202203729|doi:10.1002/chem.202203729

CCDC 1452354: Experimental Crystal Structure Determination

2016

Related Article: Negera Abdissa, Fangfang Pan, Amra Gruhonjic, Jürgen Gräfenstein, Paul A. Fitzpatrick, Göran Landberg, Kari Rissanen, Abiy Yenesew, Máté Erdélyi|2016|J.Nat.Prod.|79|2181|doi:10.1021/acs.jnatprod.6b00178