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Efficient CRISPR/Cas9 mediated large insertions using long single-stranded oligonucleotide donors in C. elegans
- The FEBS Journal
-  31 May 2023
Graphical Abstract

The use of ssDNA as repair templates provides a major advantage over dsDNA when inserting large fragments into the Caenorhabditis elegans genome with CRISPR/Cas9. A simple PCR followed by strand-selective digestion by lambda exonuclease facilitates the efficient generation of the ssDNA. Frequently, over 50% of progeny are edited, enabling simultaneous double insertions and marker-free recovery.
Increased demand for FAD synthesis in differentiated and stem pancreatic cancer cells is accomplished by modulating FLAD1 gene expression: the inhibitory effect of Chicago Sky Blue
- The FEBS Journal
-  31 May 2023
Graphical Abstract

FAD production, a crucial process for cell metabolism, is ensured by FAD synthase (FADS), coded by FLAD1. FLAD1 expression and FADS enzymatic activity significantly increase in pancreatic ductal adenocarcinoma cells and derived stem cells compared to non-malignant cells. Higher cofactor availability parallels increased levels of FAD-dependent enzymes. Thinking of FADS as a novel therapeutic target, an enzymatic inhibitor, Chicago Sky Blue, was introduced, which was able to selectively inhibit stem cell growth.
Identification of a diketopiperazine-based O-GlcNAc transferase inhibitor sensitizing hepatocellular carcinoma to CDK9 inhibition
- The FEBS Journal
-  29 May 2023
Graphical Abstract

The post-translational process O-GlcNAcylation is implicated in a variety of physiological processes and diseases, including hepatocellular carcinoma. Here, we identified HLY838, a novel diketopiperazine-based OGT inhibitor that induces a global decrease in cellular O-GlcNAcylation. HLY838 enhances the anti-HCC activity of CDK9 inhibitors both in vitro and in vivo by downregulating c-Myc and E2F1 expression. Our findings suggest that targeting O-GlcNAcylation with HLY838 may be an effective strategy to improve cancer therapy.
Regulation of PARP1 and its apoptotic variant activity by single-stranded DNA
- The FEBS Journal
-  28 May 2023
Graphical Abstract

DNA breaks recognition stimulates the catalytic activity of PARP1. Here, we have shown that Zinc-finger domains of PARP1 bind to single-strand DNA (ssDNA). Also, ssDNA acts as an activator of PARP1 activity, while poly-ADP ribose (PAR) partially hampers the ssDNA-dependent stimulation by inducing DNA dissociation. We have demonstrated that the catalytic apoptotic fragment of PARP1 is stimulated by ssDNA when complemented with a regulatory apoptotic fragment.
New insights into the structure and function of CNNM proteins
- The FEBS Journal
-  24 May 2023
Graphical Abstract

Cystathionine-β-synthase-pair domain divalent metal cation transport mediators (CNNMs) are a newly characterized class of Mg2+ transporters associated with a variety of human diseases. CNNMs are ubiquitous and found in all kingdoms of life. Here, we review recent structural and functional studies of CNNMs that have identified the transmembrane channel and clarified the regulatory role of the cytosolic domains.
The role of lysosomal membrane proteins in autophagy and related diseases
- The FEBS Journal
-  23 May 2023
New insights into the function and pathophysiology of the ectodomain sheddase A Disintegrin And Metalloproteinase 10 (ADAM10)
- The FEBS Journal
-  22 May 2023
Graphical Abstract

There is an increasing appreciation that the A Disintegrin And Metalloproteinase 10 (ADAM10) is of importance in health and disease. This review aims to summarize recent findings referring to the cell biology and pathophysiological implications of ADAM10. Its role in common and rare diseases is discussed here, with the goal to unravel ADAM10's translational potential as a target for pharmacological intervention or its use as a biomarker.
Biochemical and structural insight into the chemical resistance and cofactor specificity of the formate dehydrogenase from Starkeya novella
- The FEBS Journal
-  22 May 2023
Graphical Abstract

The biochemical and structural investigation of a bacterial formate dehydrogenase sheds light on its remarkable chemical resistance to thiol-modifying compounds. The strict specificity for the coenzyme NAD+ is changed by targeted amino acid mutations at the binding site to make the enzyme specific for NADP+. The cofactor-bound structure of a high-affinity mutant for NADP+ offers a mechanistic explanation of the successful change in cofactor specificity.
Hallmarks and evolutionary drivers of cotranslational protein complex assembly
- The FEBS Journal
-  18 May 2023
Graphical Abstract

Cotranslational assembly is a widespread mechanism for the formation of protein complexes in cells. This process depends on five hallmarks: the spatial proximity, temporal coordination, energetic stability, composition and topological arrangement of the interacting subunits. Although experiments and structural analyses have identified many properties of cotranslationally assembled complexes, their evolutionary origins and trajectories remain still largely unknown.
Screen time: an unbiased search for histone mutations that affect quiescence and chronological aging
- The FEBS Journal
-  15 May 2023
Graphical Abstract

Quiescence is essential for survival during nutrient limitations and the execution of precise developmental patterns. In yeast, entry into quiescence is associated with a loss of histone acetylation as the chromatin becomes tightly condensed. In this issue, Small and Osley performed an unbiased screen of mutations in histone H3 and H4 amino acids in budding yeast and identified histone residues that are critical for quiescence and chronological lifespan.
Resolving domain positions of cellobiose dehydrogenase by small angle X‐ray scattering
- The FEBS Journal
-  8 June 2023
Nicotinamide Riboside Activates SIRT5 Deacetylation
- The FEBS Journal
-  8 June 2023
Biophysical and biochemical nature of amorphous protein oligomers determines the strength of Immune response and the generation of T‐cell memory
- The FEBS Journal
-  7 June 2023
PTPN22 Activates PI3K Pathway via 14-3-3τ in T Cells
- The FEBS Journal
-  31 May 2023
CD24 targeting with NK‐CAR immunotherapy in testis, prostate, renal and (luminal‐type) bladder cancer and identification of direct CD24 interaction partners
- The FEBS Journal
-  31 May 2023
Binding of different hyaluronan to CD44 mediates distinct cell adhesion dynamics under shear flow
- The FEBS Journal
-  31 May 2023
Inhibition of Epithelial-to-Mesenchymal Transition Augments Antitumor Efficacy of Nanotherapeutics in Pancreatic Ductal Adenocarcinoma
- The FEBS Journal
-  28 May 2023
Crystal structure of Leptospira LSS_01692 reveals a dimeric structure and induces inflammatory responses through Toll-like receptor 2 dependent NF-κB and MAPK signal transduction pathways
- The FEBS Journal
-  27 May 2023
Efficient polyethylene terephthalate degradation at moderate temperature: a protein engineering study of LC-cutinase highlights the key role of residue 243
- The FEBS Journal
-  24 January 2023
Graphical Abstract

A truncated version of LCC cutinase was used to generate improved variants for PET degradation by an iterative semi-rational design approach. At difference from previous studies that degraded PET at temperatures ≥ 70 °C, 1.25 mg of S101N/F243T LCC depolymerized 1.3 g of untreated post-consumer PET waste in less than 3 days at 55 °C. The use of a moderate temperature makes PET enzymatic degradation more ecofriendly and sustainable.
A guide to UFMylation, an emerging posttranslational modification
- The FEBS Journal
-  20 January 2023
Graphical Abstract

UFM1 is a ubiquitin-like modifier (UBL) that is important to maintain homeostasis at the endoplasmic reticulum and mutations in this pathway lead to neurodevelopmental disorders and multiple pathologies. Being the most recently discovered UBL, we are only now beginning to understand the mechanisms and functions of this enigmatic modifier. In this review, we provide a comprehensive guide to the mechanisms and biological function of protein UFMylation.
Cellular senescence: beneficial, harmful, and highly complex
- The FEBS Journal
-  1156-1160
-  1 March 2023
Graphical Abstract

In this Editorial, Darren Baker, Masashi Narita and Pura Muñoz-Cánoves outline the content of The FEBS Journal's Special Issue on Senescence in Ageing and Disease. The issue features an exciting collection of articles that focus on the contribution of cellular senescence to a diverse range of biological processes, including normal physiology, ageing, and pathology. Importantly, the use of senolytics and senomorphics to specifically target senescent cells or their secreted components, respectively, is overviewed in several reviews of the issue.
In Conversation with John Cryan
- The FEBS Journal
-  17 January 2023
Graphical Abstract

John F. Cryan is the Principal Investigator at the APC Microbiome Ireland Institute at the University College of Cork, Ireland. His lab focuses on determining the impact of the gut microbiota on human brain and behaviour. Over the years, John has received many honours and accolades in recognition of his significant contributions to understanding the brain–gut–microbiome axis. In this interview, he outlines how he became interested in the role of the microbiome in brain development and disease, provides advice to budding scientists and highlights the broader public health implications of his research.
Cellular senescence and developmental defects
- The FEBS Journal
-  1303-1313
-  1 March 2023
Graphical Abstract

Cellular senescence is frequently induced in response to ageing and stress. Yet, studies have also uncovered beneficial functions in development, repair and regeneration. Therefore, timely and controlled induction of senescence can be beneficial, while misregulation of the senescence program contributes to disease and ageing. Here, we discuss recent studies that implicate ectopic senescence in neurodevelopmental defects and highlight how the examination of senescence in other birth defects is warranted.
Full activation of thermogenesis in brown adipocytes requires Basigin action
- The FEBS Journal
-  2673-2691
-  3 January 2023
Graphical Abstract

A better understanding of underlying mechanisms mediating the remarkable energy-dissipating capacity of brown adipose tissue (BAT) is necessary to explore its therapeutic potential for the treatment of obesity. Here, we reveal the dynamic regulation of a transmembrane protein Basigin in BAT and its previously uncharacterized role in brown fat function. We demonstrate that Basigin controls key processes crucial for the proper activation of BAT including Ucp1 expression, lipolysis and cellular metabolism.
A tyrosine-based YXXΦ motif regulates the degradation of aquaporin-4 via both lysosomal and proteasomal pathways and is functionally inhibited by a 10-amino-acid sequence within its C-terminus
- The FEBS Journal
-  2616-2635
-  4 January 2023
Graphical Abstract

A tyrosine-based YXXΦ motif in the C-terminal domain plays a critical role in the steady-state subcellular localization/turnover and antibody-induced endocytosis/lysosomal degradation of AQP4. The C-terminal 10-amino-acid sequence including two negatively charged amino acids (D314 and E318) functionally competes with the YXXΦ motif and stabilizes AQP4. The YXXΦ motif also functions as a signal to degrade AQP4 using proteasomes.
Multiple enzymatic approaches to hydrolysis of fungal β-glucans by the soil bacterium Chitinophaga pinensis
- The FEBS Journal
-  2909-2922
-  6 January 2023
Graphical Abstract

The soil bacterium Chitinophaga pinensis secretes a cocktail of enzymes that can deconstruct complex fungal cell walls, releasing sugars to be used for metabolism. Three such enzymes, from different glycoside hydrolase families, are characterised in this study. They use different strategies to interact with fungal β-1,6-glucan (pustulan), leading to different efficiencies in polysaccharide breakdown. This work shows how diverse enzymatic approaches can be used to target a recalcitrant substrate.
Interaction network among de novo purine nucleotide biosynthesis enzymes in Escherichia coli
- The FEBS Journal
-  7 February 2023
Graphical Abstract

Metabolic pathways are regulated through the formation of metabolons. Using a two-hybrid approach, we demonstrate a dense protein interaction network among the enzymes of the E. coli de novo purine nucleotide biosynthesis. Alterations of this network through mutations impact purine nucleotide pools and bacterial fitness. Our data suggest that the bacterial de novo purine nucleotide biosynthesis enzymes assemble in a supramolecular complex and proper interactions within it contribute to bacterial fitness.
Recreating the extracellular matrix: novel 3D cell culture platforms in cancer research
- The FEBS Journal
-  17 March 2023
Graphical Abstract

The microenvironment of three-dimensional (3D) cell culture systems closely mimics the in vivo tumour conditions. Cancer cells in 3D platforms secrete a plethora of matrix effectors in the provisional matrix often in higher bioavailability compared with two-dimensional (2D) cell cultures. The exploration of the 3D matrix architectures in advanced cell culture platforms generated through cutting-edge technologies may fill the gap between preclinical cancer research and applied cancer therapeutics.
ADP‐ribosyltransferases, an update on function and nomenclature
- The FEBS Journal
-  7399-7410
-  29 July 2021
Graphical Abstract

ADP-ribosylation, the transfer of ADP-ribose from NAD+ onto substrates, is catalyzed by proteins with an ADP-ribosyltransferase (ART) domain. This fully reversible modification can occur as mono- or poly-ADP-ribosylation. Here, we propose an updated nomenclature for mammalian ARTs and provide a brief description of the main functions of these proteins to illustrate the increasing diversity of the cellular processes that are regulated by mono- and poly-ADP-ribosylation.
Targeting cellular senescence with senotherapeutics: senolytics and senomorphics
- The FEBS Journal
-  1362-1383
-  11 January 2022
Graphical Abstract

Cellular senescence, a critical hallmark of ageing, has been shown to drive many age-associated chronic diseases. Senescent cells (SnCs) up-regulate pathways associated with evasion of apoptosis, survival, senescence-associated secretory phenotype (SASP) development and others that are targeted using senotherapeutics. Senotherapeutics selectively target SnCs for their clearance (senolytics) or suppression of their SASP (senomorphics). Many studies have demonstrated the benefit of senotherapeutic treatment for the extension of health and lifespan.
The mitochondrial permeability transition: Recent progress and open questions
- The FEBS Journal
-  7051-7074
-  28 October 2021
Graphical Abstract

The mechanistic basis for the mitochondrial permeability transition (an inner membrane permeability increase that is a causative event in cell death) has puzzled mitochondrial research for 70 years. Here, we review the field and discuss recent evidence on how a Ca2+-dependent conformational change of F-ATP synthase and of adenine nucleotide translocator may transform these energy-conserving devices into energy-dissipating multiconductance channels causing the permeability transition.
Indoleamine 2,3‐dioxygenase 1 (IDO1): an up‐to‐date overview of an eclectic immunoregulatory enzyme
- The FEBS Journal
-  6099-6118
-  19 June 2021
Graphical Abstract

IDO1 has a complex functional dynamics capable of fulfilling distinct environmental needs. Besides its catalytic activity degrading tryptophan, IDO1 performs a non-enzymic function that, via activation of SHP1/SHP2 and noncanonical NF-κB, reprograms the expression profile of dendritic cells (DCs) towards a long-term immunoregulatory phenotype. The distinct functions occur either in cytosol (enzymic) or in early endosomes (EE; non-enzymic). In inflammatory conditions, IDO1 is shut down by SOCS3-mediated proteasomal degradation, and an immunostimulatory program is acquired by the DCs.
Nuclear speckles: dynamic hubs of gene expression regulation
- The FEBS Journal
-  7234-7245
-  10 July 2021
Graphical Abstract

In this review, nuclear speckles (NS) are revisited in the light of most recent findings about the composition of NS, the role of NS in gene expression regulation and genome architecture, and the evolutionary origins of NS. The long road to understanding the function of NS is also discussed based on these new connections to gene expression regulation and molecular origins of NS. Created with BioRender.com.
Long‐term plasticity in the hippocampus: maintaining within and ‘tagging’ between synapses
- The FEBS Journal
-  2176-2201
-  10 June 2021
Graphical Abstract

Synaptic plasticity permits bidirectional modification of synapses and likely is a cellular correlate of learning and memory. Synaptic tagging and capture enables synapses to interact with one another, underpinning associative learning. We describe how several key molecular players and cellular events promote, restrict or modulate homosynaptic and heterosynaptic forms of plasticity. Focusing on the hippocampus, we discuss recent advances in synaptic plasticity, its molecular interactions and behavioural implications.
Global functions of O‐glycosylation: promises and challenges in O‐glycobiology
- The FEBS Journal
-  7183-7212
-  4 August 2021
Graphical Abstract

With a genetic entry point and new technologies, we are beginning to define functions related to mucin-type O-glycosylation. This includes protection from proteolytic cleavage, modulation of receptor functions, homing and modulation of immune cells, and functions in cell adhesion, metabolism, and host–microbiome interactions. This review presents the achievements and promises in O-GalNAc glycobiology driven by technological advances in analytical methods, genetic engineering, and systems biology.
Migrasome biogenesis and functions
- The FEBS Journal
-  7246-7254
-  7 September 2021
Graphical Abstract

Migrasomes are newly found organelles produced by migrating cells and grow on retraction fibers trailing behind the cells. Migrasomes are produced as a result of tetraspanin-enriched macrodomain accumulation and could be released into the extracellular matrix or engulfed by other cells. Migrasomes could act as carriers of mRNA, protein, or damaged mitochondria, or as chemoattractive sources.
LD‐transpeptidases: the great unknown among the peptidoglycan cross‐linkers
- The FEBS Journal
-  4718-4730
-  10 June 2021
Graphical Abstract

Peptidoglycan cross-linking enzymes LD-transpeptidases (LDTs) have kept an aura of mystery for a long time. However, a number of recent reports have linked the activity of LDTs to cell wall adaptation to stress including β-lactam antibiotics, outer membrane stability, and toxin delivery. Critically, in some bacteria, LDT activity has a major—even essential—role in PG biosynthesis. In this review, we discuss general and species-specific functions enabled by LD cross-links.
A guide to the Michaelis–Menten equation: steady state and beyond
- The FEBS Journal
-  6086-6098
-  16 July 2021
Graphical Abstract

The article talks about the primacy of the Michaelis–Menten equation as a framework for the quantitative understanding of enzyme kinetics. It dwells upon the mathematical elegance of and the assumptions that went into framing the equation. Further, it traces the history of the equation and the growth of the field beyond it. The image shows an artistic rendering of the crowded interiors of a cell and the equation dictating how macromolecular interactions of catalytic nature happen.