journal
https://read.qxmd.com/read/38695682/let-s-get-fat-emergence-of-s-acylation-as-a-therapeutic-target-in-huntington-disease
#41
JOURNAL ARTICLE
Dale D O Martin, Shaun S Sanders
Protein mislocalization is a key initial step in neurodegeneration, regardless of etiology, and has been linked to changes in the dynamic addition of saturated fatty acids to proteins, a process known as S-acylation. With the advent of new techniques to study S-acylation and the recent discovery of new enzymes that facilitate protein deacylation, novel small molecules are emerging as potential new therapeutic treatments. Huntington disease (HD) is a devastating, fatal neurodegenerative disease characterized by motor, cognitive, and psychiatric deficits caused by a CAG repeat expansion in the HTT gene...
May 2, 2024: Biochemical Society Transactions
https://read.qxmd.com/read/38666616/raman-spectroscopy-in-the-study-of-amyloid-formation-and-phase-separation
#42
JOURNAL ARTICLE
Sashary Ramos, Jennifer C Lee
Neurodegenerative diseases, such as Alzheimer's and Parkinson's, share a common pathological feature of amyloid structure accumulation. However, the structure-function relationship between these well-ordered, β-sheet-rich, filamentous protein deposits and disease etiology remains to be defined. Recently, an emerging hypothesis has linked phase separation, a process involved in the formation of protein condensates, to amyloid formation, suggesting that liquid protein droplets serve as loci for amyloid initiation...
April 26, 2024: Biochemical Society Transactions
https://read.qxmd.com/read/38666605/the-swi-snf-chromatin-remodeling-complex-a-critical-regulator-of-metabolism
#43
JOURNAL ARTICLE
Michael C Church, Jerry L Workman
The close relationship between chromatin and metabolism has been well-studied in recent years. Many metabolites have been found to be cofactors used to modify chromatin, and these modifications can in turn affect gene transcription. One chromatin-associated factor responsible for regulating transcription is the SWI/SNF complex, an ATP-dependent chromatin remodeler conserved throughout eukaryotes. SWI/SNF was originally described in yeast as regulating genes involved in carbon source metabolism and mating type switching, and its mammalian counterpart has been extensively studied for its role in diseases such as cancer...
April 26, 2024: Biochemical Society Transactions
https://read.qxmd.com/read/38666604/from-bottom-up-to-cell-surface-proteomics-detergents-or-no-detergents-that-is-the-question
#44
JOURNAL ARTICLE
Zora Brough, Zhiyu Zhao, Franck Duong van Hoa
Measuring the expression levels of membrane proteins (MPs) is crucial for understanding cell differentiation and tissue specificity, defining disease characteristics, identifying biomarkers, and developing therapeutics. While bottom-up proteomics addresses the need for accurately surveying the membrane proteome, the lower abundance and hydrophobic nature of MPs pose challenges in sample preparation. As MPs normally reside in the lipid bilayer, conventional extraction methods rely on detergents, introducing here a paradox - detergents prevent aggregation and facilitate protein processing, but themselves become contaminants that interfere with downstream analytical applications...
April 26, 2024: Biochemical Society Transactions
https://read.qxmd.com/read/38666598/the-choreography-of-chromatin-in-rna-polymerase-iii-regulation
#45
JOURNAL ARTICLE
Maria Elize van Breugel, Alan Gerber, Fred van Leeuwen
Regulation of eukaryotic gene expression involves a dynamic interplay between the core transcriptional machinery, transcription factors, and chromatin organization and modification. While this applies to transcription by all RNA polymerase complexes, RNA polymerase III (RNAPIII) seems to be atypical with respect to its mechanisms of regulation. One distinctive feature of most RNAPIII transcribed genes is that they are devoid of nucleosomes, which relates to the high levels of transcription. Moreover, most of the regulatory sequences are not outside but within the transcribed open chromatin regions...
April 26, 2024: Biochemical Society Transactions
https://read.qxmd.com/read/38661212/the-importance-of-muscle-glycogen-phosphorylase-in-glial-cells-function
#46
JOURNAL ARTICLE
Francisco Llavero, José L Zugaza
The three isoforms of glycogen phosphorylase - PYGM, PYGB, and PYGL - are expressed in glial cells. Unlike PYGB and PYGL, PYGM is the only isoform regulated by Rac1. This specific regulation may confer a differential functional role compared with the other glycogen phosphorylases-PYGB and PYGL. The involvement of muscle glycogen phosphorylase in glial cells and its association with post-translational modifications (PTMs) of proteins through O-glycosylation is indeed a fascinating and emerging area of research...
April 25, 2024: Biochemical Society Transactions
https://read.qxmd.com/read/38661189/exploring-potential-developmental-origins-of-common-neurodegenerative-disorders
#47
JOURNAL ARTICLE
James P Catlin, Christine E Schaner Tooley
In the United States, it is now estimated that 6.7 million people over the age of 65 are afflicted by Alzheimer's disease (AD), over 1 million people are living with Parkinson's disease (PD), and over 200 000 have or are at risk for developing Huntington's disease (HD). All three of these neurodegenerative diseases result in the ultimate death of distinct neuronal subtypes, and it is widely thought that age-related damage is the single biggest contributing factor to this neuronal death. However, recent studies are now suggesting that developmental defects during early neurogenesis could also play a role in the pathology of neurodegenerative diseases...
April 25, 2024: Biochemical Society Transactions
https://read.qxmd.com/read/38630434/inorganic-polyphosphate-and-ion-transport-across-biological-membranes
#48
JOURNAL ARTICLE
Yaw Akosah, Jingyi Yang, Evgeny Pavlov
Inorganic polyphosphate (polyP) is widely recognized for playing important roles and processes involved in energy and phosphate storage, regulation of gene expression, and calcium signaling. The less well-known role of polyP is as a direct mediator of ion transport across biological membranes. Here, we will briefly summarize current knowledge of the molecular mechanisms of how polyP can be involved in membrane ion transport. We discuss three types of mechanisms that might involve polyP: (1) formation of non-protein channel complex that includes calcium, polyP, and polyhydroxybutyrate (PHB); (2) modulation of the channel activity of PHBlated protein channels; and (3) direct effects of polyP on the function of the voltage-gated ion channels in the process that do not involve PHB...
April 17, 2024: Biochemical Society Transactions
https://read.qxmd.com/read/38629725/covalent-activity-based-probes-for-imaging-of-serine-proteases
#49
JOURNAL ARTICLE
Marcin Skorenski, Shanping Ji, Steven H L Verhelst
Serine proteases are one of the largest mechanistic classes of proteases. They regulate a plethora of biochemical pathways inside and outside the cell. Aberrant serine protease activity leads to a wide variety of human diseases. Reagents to visualize these activities can be used to gain insight into the biological roles of serine proteases. Moreover, they may find future use for the detection of serine proteases as biomarkers. In this review, we discuss small molecule tools to image serine protease activity...
April 17, 2024: Biochemical Society Transactions
https://read.qxmd.com/read/38629718/new-insights-into-the-structure-and-dynamics-of-the-tom-complex-in-mitochondria
#50
JOURNAL ARTICLE
Stephan Nussberger, Robin Ghosh, Shuo Wang
To date, there is no general physical model of the mechanism by which unfolded polypeptide chains with different properties are imported into the mitochondria. At the molecular level, it is still unclear how transit polypeptides approach, are captured by the protein translocation machinery in the outer mitochondrial membrane, and how they subsequently cross the entropic barrier of a protein translocation pore to enter the intermembrane space. This deficiency has been due to the lack of detailed structural and dynamic information about the membrane pores...
April 17, 2024: Biochemical Society Transactions
https://read.qxmd.com/read/38629716/deconstructing-cancer-with-precision-genome-editing
#51
JOURNAL ARTICLE
Grace A Johnson, Samuel I Gould, Francisco J Sánchez-Rivera
Recent advances in genome editing technologies are allowing investigators to engineer and study cancer-associated mutations in their endogenous genetic contexts with high precision and efficiency. Of these, base editing and prime editing are quickly becoming gold-standards in the field due to their versatility and scalability. Here, we review the merits and limitations of these precision genome editing technologies, their application to modern cancer research, and speculate how these could be integrated to address future directions in the field...
April 17, 2024: Biochemical Society Transactions
https://read.qxmd.com/read/38629643/sumo-and-the-dna-damage-response
#52
JOURNAL ARTICLE
Jai S Bhachoo, Alexander J Garvin
The preservation of genome integrity requires specialised DNA damage repair (DDR) signalling pathways to respond to each type of DNA damage. A key feature of DDR is the integration of numerous post-translational modification signals with DNA repair factors. These modifications influence DDR factor recruitment to damaged DNA, activity, protein-protein interactions, and ultimately eviction to enable access for subsequent repair factors or termination of DDR signalling. SUMO1-3 (small ubiquitin-like modifier 1-3) conjugation has gained much recent attention...
April 17, 2024: Biochemical Society Transactions
https://read.qxmd.com/read/38629637/rna-m6a-modification-signals-for-degradation-or-stabilisation
#53
JOURNAL ARTICLE
Guifeng Wei
The RNA modification N6-methyladenosine (m6A) is conserved across eukaryotes, and profoundly influences RNA metabolism, including regulating RNA stability. METTL3 and METTL14, together with several accessory components, form a 'writer' complex catalysing m6A modification. Conversely, FTO and ALKBH5 function as demethylases, rendering m6A dynamic. Key to understanding the functional significance of m6A is its 'reader' proteins, exemplified by YTH-domain-containing proteins (YTHDFs) canonical reader and insulin-like growth factor 2 mRNA-binding proteins (IGF2BPs) non-canonical reader...
April 17, 2024: Biochemical Society Transactions
https://read.qxmd.com/read/38629629/therapeutic-exploitation-of-ferroptosis
#54
JOURNAL ARTICLE
Magali Walravens, Ine Koeken, Tom Vanden Berghe
Pathological breakdown of membrane lipids through excessive lipid peroxidation (LPO) was first described in the mid-20th century and is now recognized as a form of regulated cell death, dubbed ferroptosis. Accumulating evidence unveils how metabolic regulation restrains peroxidation of phospholipids within cellular membranes, thereby impeding ferroptosis execution. Unleashing these metabolic breaks is currently therapeutically explored to sensitize cancers to ferroptosis inducing anti-cancer therapies. Reversely, these natural ferroptotic defense mechanisms can fail resulting in pathological conditions or diseases such as ischemia-reperfusion injury, multi-organ dysfunction, stroke, infarction, or neurodegenerative diseases...
April 17, 2024: Biochemical Society Transactions
https://read.qxmd.com/read/38629621/the-ring-rules-the-chain-inositol-pyrophosphates-and-the-regulation-of-inorganic-polyphosphate
#55
JOURNAL ARTICLE
Azmi Khan, Manisha Mallick, Jayashree S Ladke, Rashna Bhandari
The maintenance of phosphate homeostasis serves as a foundation for energy metabolism and signal transduction processes in all living organisms. Inositol pyrophosphates (PP-InsPs), composed of an inositol ring decorated with monophosphate and diphosphate moieties, and inorganic polyphosphate (polyP), chains of orthophosphate residues linked by phosphoanhydride bonds, are energy-rich biomolecules that play critical roles in phosphate homeostasis. There is a complex interplay between these two phosphate-rich molecules, and they share an interdependent relationship with cellular adenosine triphosphate (ATP) and inorganic phosphate (Pi)...
April 17, 2024: Biochemical Society Transactions
https://read.qxmd.com/read/38629612/myosin-xi-a-model-of-its-conserved-role-in-plant-cell-tip-growth
#56
JOURNAL ARTICLE
Edward J Chocano-Coralla, Luis Vidali
In eukaryotic cells, organelle and vesicle transport, positioning, and interactions play crucial roles in cytoplasmic organization and function. These processes are governed by intracellular trafficking mechanisms. At the core of that trafficking, the cytoskeleton and directional transport by motor proteins stand out as its key regulators. Plant cell tip growth is a well-studied example of cytoplasm organization by polarization. This polarization, essential for the cell's function, is driven by the cytoskeleton and its associated motors...
April 17, 2024: Biochemical Society Transactions
https://read.qxmd.com/read/38600027/atomic-force-microscopy-3d-structural-reconstruction-of-individual-particles-in-the-study-of-amyloid-protein-assemblies
#57
JOURNAL ARTICLE
Claudia Chitty, Kinga Kuliga, Wei-Feng Xue
Recent developments in atomic force microscopy (AFM) image analysis have made three-dimensional (3D) structural reconstruction of individual particles observed on 2D AFM height images a reality. Here, we review the emerging contact point reconstruction AFM (CPR-AFM) methodology and its application in 3D reconstruction of individual helical amyloid filaments in the context of the challenges presented by the structural analysis of highly polymorphous and heterogeneous amyloid protein structures. How individual particle-level structural analysis can contribute to resolving the amyloid polymorph structure-function relationships, the environmental triggers leading to protein misfolding and aggregation into amyloid species, the influences by the conditions or minor fluctuations in the initial monomeric protein structure on the speed of amyloid fibril formation, and the extent of the different types of amyloid species that can be formed, are discussed...
April 11, 2024: Biochemical Society Transactions
https://read.qxmd.com/read/38600022/post-translational-modifications-emerging-directors-of-cell-fate-decisions-during-endoplasmic-reticulum-stress-in-arabidopsis-thaliana
#58
JOURNAL ARTICLE
Ethan Thibault, Federica Brandizzi
Homeostasis of the endoplasmic reticulum (ER) is critical for growth, development, and stress responses. Perturbations causing an imbalance in ER proteostasis lead to a potentially lethal condition known as ER stress. In ER stress situations, cell-fate decisions either activate pro-life pathways that reestablish homeostasis or initiate pro-death pathways to prevent further damage to the organism. Understanding the mechanisms underpinning cell-fate decisions in ER stress is critical for crop development and has the potential to enable translation of conserved components to ER stress-related diseases in metazoans...
April 11, 2024: Biochemical Society Transactions
https://read.qxmd.com/read/38572966/decoding-the-ubiquitin-landscape-by-cutting-edge-ubiquitinomic-approaches
#59
JOURNAL ARTICLE
Brindhavanam P T, Indrajit Sahu
Functional consequences of protein ubiquitination have gone far beyond the degradation regulation as was initially imagined during its discovery 40 years back. The state-of-the-art has revealed the plethora of signaling pathways that are largely regulated by ubiquitination process in eukaryotes. To no surprise, ubiquitination is often dysregulated in many human diseases, including cancer, neurodegeneration and infection. Hence it has become a major focus with high-gain research value for many investigators to unravel new proteoforms, that are the targets of this ubiquitination modification...
April 4, 2024: Biochemical Society Transactions
https://read.qxmd.com/read/38572912/the-swi-snf-atp-dependent-chromatin-remodeling-complex-in-cell-lineage-priming-and-early-development
#60
JOURNAL ARTICLE
Dhurjhoti Saha, Srinivas Animireddy, Blaine Bartholomew
ATP dependent chromatin remodelers have pivotal roles in transcription, DNA replication and repair, and maintaining genome integrity. SWI/SNF remodelers were first discovered in yeast genetic screens for factors involved in mating type switching or for using alternative energy sources therefore termed SWI/SNF complex (short for SWItch/Sucrose NonFermentable). The SWI/SNF complexes utilize energy from ATP hydrolysis to disrupt histone-DNA interactions and shift, eject, or reposition nucleosomes making the underlying DNA more accessible to specific transcription factors and other regulatory proteins...
April 4, 2024: Biochemical Society Transactions
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