journal
https://read.qxmd.com/read/38270460/the-mtorc2-signaling-network-targets-and-cross-talks
#21
JOURNAL ARTICLE
Aparna Ragupathi, Christian Kim, Estela Jacinto
The mechanistic target of rapamycin, mTOR, controls cell metabolism in response to growth signals and stress stimuli. The cellular functions of mTOR are mediated by two distinct protein complexes, mTOR complex 1 (mTORC1) and mTORC2. Rapamycin and its analogs are currently used in the clinic to treat a variety of diseases and have been instrumental in delineating the functions of its direct target, mTORC1. Despite the lack of a specific mTORC2 inhibitor, genetic studies that disrupt mTORC2 expression unravel the functions of this more elusive mTOR complex...
January 25, 2024: Biochemical Journal
https://read.qxmd.com/read/38174858/pseudouridylation-mediated-gene-expression-modulation
#22
REVIEW
Jonathan L Chen, W-Matthias Leeder, Pedro Morais, Hironori Adachi, Yi-Tao Yu
RNA-guided pseudouridylation, a widespread post-transcriptional RNA modification, has recently gained recognition for its role in cellular processes such as pre-mRNA splicing and the modulation of premature termination codon (PTC) readthrough. This review provides insights into its mechanisms, functions, and potential therapeutic applications. It examines the mechanisms governing RNA-guided pseudouridylation, emphasizing the roles of guide RNAs and pseudouridine synthases in catalyzing uridine-to-pseudouridine conversion...
January 10, 2024: Biochemical Journal
https://read.qxmd.com/read/38108461/correction-mechanism-of-sphingosine-1-phosphate-clearance-from-blood
#23
Yugesh Kharel, Tao Huang, Anita Salamon, Thurl E Harris, Webster L Santos, Kevin R Lynch
No abstract text is available yet for this article.
December 20, 2023: Biochemical Journal
https://read.qxmd.com/read/38100320/into-the-fold-advances-in-understanding-apkc-membrane-dynamics
#24
JOURNAL ARTICLE
Mathias Cobbaut, Peter J Parker, Neil Q McDonald
Atypical protein kinase Cs (aPKCs) are part of the PKC family of protein kinases and are atypical because they don't respond to the canonical PKC activators diacylglycerol (DAG) and Ca2+. They are central to the organization of polarized cells and are deregulated in several cancers. aPKC recruitment to the plasma membrane compartment is crucial to their encounter with substrates associated with polarizing functions. However, in contrast with other PKCs, the mechanism by which atypical PKCs are recruited there has remained elusive until recently...
December 20, 2023: Biochemical Journal
https://read.qxmd.com/read/38063234/engineering-of-cyp82y1-a-cytochrome-p450-monooxygenase-a-key-enzyme-in-noscapine-biosynthesis-in-opium-poppy
#25
JOURNAL ARTICLE
Zahra Aghaali, Mohammad Reza Naghavi
Protein engineering provides a powerful base for the circumvention of challenges tied with characteristics accountable for enzyme functions. CYP82Y1 introduces a hydroxyl group (-OH) into C1 of N-methylcanadine as the substrate to yield 1-hydroxy-N-methylcanadine. This chemical process has been found to be the gateway to noscapine biosynthesis. Owning to the importance of CYP82Y1 in this biosynthetic pathway, it has been selected as a target for enzyme engineering. The insertion of tags to the N- and C-terminal of CYP82Y1 was assessed for their efficiencies for improvement of the physiological performances of CYP82Y1...
December 13, 2023: Biochemical Journal
https://read.qxmd.com/read/38054592/lysine-methylation-signaling-in-skeletal-muscle-biology-from-myogenesis-to-clinical-insights
#26
JOURNAL ARTICLE
Eric Cordeiro-Spinetti, Scott B Rothbart
Lysine methylation signaling is well studied for its key roles in the regulation of transcription states through modifications on histone proteins. While histone lysine methylation has been extensively studied, recent discoveries of lysine methylation on thousands of non-histone proteins has broadened our appreciation for this small chemical modification in the regulation of protein function. In this review, we highlight the significance of histone and non-histone lysine methylation signaling in skeletal muscle biology, spanning development, maintenance, regeneration, and disease progression...
December 13, 2023: Biochemical Journal
https://read.qxmd.com/read/38054591/understanding-interleukin-11-as-a-disease-gene-and-therapeutic-target
#27
JOURNAL ARTICLE
Stuart A Cook
Interleukin 11 (IL11) is an elusive member of the IL6 family of cytokines. While initially thought to be a haematopoietic and cytoprotective factor, more recent data show instead that IL11 is redundant for haematopoiesis and toxic. In this review, the reasons that led to the original misunderstandings of IL11 biology, which are now understandable, are explained with particular attention on the use of recombinant human IL11 in mice and humans. Following tissue injury, as part of an evolutionary ancient homeostatic response, IL11 is secreted from damaged mammalian cells to signal via JAK/STAT3, ERK/P90RSK, LKB1/mTOR and GSK3β/SNAI1 in autocrine and paracrine...
December 13, 2023: Biochemical Journal
https://read.qxmd.com/read/38038975/a-guide-to-erk-dynamics-part-2-downstream-decoding
#28
JOURNAL ARTICLE
Abhineet Ram, Devan Murphy, Nicholaus DeCuzzi, Madhura Patankar, Jason Hu, Michael Pargett, John G Albeck
Signaling by the extracellular signal-regulated kinase (ERK) pathway controls many cellular processes, including cell division, death, and differentiation. In this second installment of a two-part review, we address the question of how the ERK pathway exerts distinct and context-specific effects on multiple processes. We discuss how the dynamics of ERK activity induce selective changes in gene expression programs, with insights from both experiments and computational models. With a focus on single-cell biosensor-based studies, we summarize four major functional modes for ERK signaling in tissues: adjusting the size of cell populations, gradient-based patterning, wave propagation of morphological changes, and diversification of cellular gene expression states...
December 13, 2023: Biochemical Journal
https://read.qxmd.com/read/38038974/a-guide-to-erk-dynamics-part-1-mechanisms-and-models
#29
JOURNAL ARTICLE
Abhineet Ram, Devan Murphy, Nicholaus DeCuzzi, Madhura Patankar, Jason Hu, Michael Pargett, John G Albeck
Extracellular signal-regulated kinase (ERK) has long been studied as a key driver of both essential cellular processes and disease. A persistent question has been how this single pathway is able to direct multiple cell behaviors, including growth, proliferation, and death. Modern biosensor studies have revealed that the temporal pattern of ERK activity is highly variable and heterogeneous, and critically, that these dynamic differences modulate cell fate. This two-part review discusses the current understanding of dynamic activity in the ERK pathway, how it regulates cellular decisions, and how these cell fates lead to tissue regulation and pathology...
December 13, 2023: Biochemical Journal
https://read.qxmd.com/read/38038973/skin-in-the-game-pannexin-channels-in-healthy-and-cancerous-skin
#30
JOURNAL ARTICLE
Brooke L O'Donnell, Silvia Penuela
The skin is a highly organized tissue composed of multiple layers and cell types that require coordinated cell to cell communication to maintain tissue homeostasis. In skin cancer, this organized structure and communication is disrupted, prompting the malignant transformation of healthy cells into melanoma, basal cell carcinoma or squamous cell carcinoma tumours. One such family of channel proteins critical for cellular communication is pannexins (PANX1, PANX2, PANX3), all of which are present in the skin. These heptameric single-membrane channels act as conduits for small molecules and ions like ATP and Ca2+ but have also been shown to have channel-independent functions through their interacting partners or action in signalling pathways...
December 13, 2023: Biochemical Journal
https://read.qxmd.com/read/38032258/the-role-of-phosphorylation-in-calmodulin-mediated-gating-of-human-aqp0
#31
JOURNAL ARTICLE
Stefan Kreida, Jennifer Virginia Roche, Julie Winkel Missel, Tamim Al-Jubair, Carl Johan Hagströmer, Veronika Wittenbecher, Sara Linse, Pontus Gourdon, Susanna Törnroth-Horsefield
Aquaporin-0 (AQP0) is the main water channel in the mammalian lens and is involved in accommodation and maintaining lens transparency. AQP0 binds the Ca2+-sensing protein calmodulin (CaM) and this interaction is believed to gate its water permeability by closing the water-conducting pore. Here we express recombinant and functional human AQP0 in P. pastoris and investigate how phosphorylation affects the interaction with CaM in vitro as well as the CaM-dependent water permeability of AQP0 in proteoliposomes...
November 30, 2023: Biochemical Journal
https://read.qxmd.com/read/37994913/plant-adaptation-to-climate-change
#32
JOURNAL ARTICLE
Christine H Foyer, Ilse Kranner
Plants are vital to human health and well-being, as well as helping to protect the environment against the negative impacts of climate change. They are an essential part of the 'One Health' strategy that seeks to balance and optimize the health of people, animals and the environment. Crucially, plants are central to nature-based solutions to climate mitigation, not least because soil carbon storage is an attractive strategy for mitigating greenhouse gas emissions and the associated climate change. Agriculture depends on genetically pure, high-quality seeds that are free from pests and pathogens and contain a required degree of genetic purity...
November 29, 2023: Biochemical Journal
https://read.qxmd.com/read/37991346/enzyme-function-and-evolution-through-the-lens-of-bioinformatics
#33
JOURNAL ARTICLE
Antonio J M Ribeiro, Ioannis G Riziotis, Neera Borkakoti, Janet M Thornton
Enzymes have been shaped by evolution over billions of years to catalyse the chemical reactions that support life on earth. Dispersed in the literature, or organised in online databases, knowledge about enzymes can be structured in distinct dimensions, either related to their quality as biological macromolecules, such as their sequence and structure, or related to their chemical functions, such as the catalytic site, kinetics, mechanism, and overall reaction. The evolution of enzymes can only be understood when each of these dimensions is considered...
November 29, 2023: Biochemical Journal
https://read.qxmd.com/read/37975605/elevated-atmospheric-carbon-dioxide-and-plant-immunity-to-fungal-pathogens-do-the-risks-outweigh-the-benefits
#34
JOURNAL ARTICLE
Freya Smith, Estrella Luna
Anthropogenic emissions have caused atmospheric carbon dioxide (CO2) concentrations to double since the industrial revolution. Although this could benefit plant growth from the 'CO2 fertilisation' effect, recent studies report conflicting impacts of elevated CO2 (eCO2) on plant-pathogen interactions. Fungal pathogens are the leading cause of plant disease. Since climate change has been shown to affect the distribution and virulence of these pathogens, it is important to understand how their plant hosts may also respond...
November 29, 2023: Biochemical Journal
https://read.qxmd.com/read/38014506/sperm-induce-a-secondary-increase-in-atp-levels-in-mouse-eggs-that-is-independent-of-ca2-oscillations
#35
JOURNAL ARTICLE
Cindy Ikie-Eshalomi, Elnur Aliyev, Sven Hoehn, Thomasz Jukowski, Karl Swann
Egg activation at fertilization in mouse eggs is caused by a series of cytosolic Ca2+ oscillations that are associated with an increase in ATP concentrations driven by increased mitochondrial activity. We have investigated the role of Ca2+ oscillations in these changes in ATP at fertilization by measuring the dynamics of ATP and Ca2+ in mouse eggs. An initial ATP increase started with the first Ca2+ transient at fertilization and then a secondary increase in ATP occurred about 1 hour later and this preceded a small and temporary increase in the frequency of Ca2+ oscillations...
November 28, 2023: Biochemical Journal
https://read.qxmd.com/read/38014500/leukotriene-b4-receptor-1-blt1-does-not-mediate-disease-progression-in-a-mouse-model-of-liver-fibrosis
#36
JOURNAL ARTICLE
Erin Coyne, Yilin Nie, Desiree Abdurrachim, Charlene Lin Zhi Ong, Yongqi Zhou, Asad Abu Bakar Ali, Stacey Meyers, Jeff Grein, Wendy Blumenschein, Brendan Gongol, Yang Liu, Cedric Lorenz Hugelshofer, Ester Carballo-Jane, Saswata Talukdar
MASH is a prevalent liver disease that can progress to fibrosis, cirrhosis, hepatocellular carcinoma (HCC), and ultimately death, but there are no approved therapies. Leukotriene B4 (LTB4) is a potent pro-inflammatory chemoattractant that drives macrophage and neutrophil chemotaxis, and genetic loss or inhibition of its high affinity receptor, leukotriene B4 receptor 1 (BLT1), results in improved insulin sensitivity and decreased hepatic steatosis. To validate the therapeutic efficacy of BLT1 inhibition in an inflammatory and pro-fibrotic mouse model of MASH and fibrosis, mice were challenged with a choline-deficient, L-amino acid defined high fat diet and treated with a BLT1 antagonist at 30 or 90 mg/kg for 8 weeks...
November 28, 2023: Biochemical Journal
https://read.qxmd.com/read/37965929/interactions-of-mitochondrial-and-skeletal-muscle-biology-in-mitochondrial-myopathy
#37
JOURNAL ARTICLE
Valeria Di Leo, Tiago M Bernardino Gomes, Amy E Vincent
Mitochondrial dysfunction in skeletal muscle fibres occurs with both healthy aging and a range of neuromuscular diseases. The impact of mitochondrial dysfunction in skeletal muscle and the way muscle fibres adapt to this dysfunction is important to understand disease mechanisms and to develop therapeutic interventions. Furthermore, interactions between mitochondrial dysfunction and skeletal muscle biology, in mitochondrial myopathy, likely have important implications for normal muscle function and physiology...
November 15, 2023: Biochemical Journal
https://read.qxmd.com/read/37916895/targeting-bacterial-degradation-machinery-as-an-antibacterial-strategy
#38
JOURNAL ARTICLE
Radoslav Petkov, Amy H Camp, Rivka L Isaacson, James H Torpey
The exploitation of a cell's natural degradation machinery for therapeutic purposes is an exciting research area in its infancy with respect to bacteria. Here, we review current strategies targeting the ClpCP system, which is a proteolytic degradation complex essential in the biology of many bacterial species of scientific interest. Strategies include using natural product antibiotics or acyldepsipeptides to initiate the up- or down-regulation of ClpCP activity. We also examine exciting recent forays into BacPROTACs to trigger the degradation of specific proteins of interest through the hijacking of the ClpCP machinery...
November 15, 2023: Biochemical Journal
https://read.qxmd.com/read/37943248/elucidating-the-interaction-of-c-terminal-domain-of-vaccinia-related-kinase2a-vrk2a-with-b-cell-lymphoma-extra-large-bcl-xl-to-decipher-its-anti-apoptotic-role-in-cancer
#39
JOURNAL ARTICLE
Rashmi Puja, Shubhankar Dutta, Kakoli Bose
Vaccinia-Related Kinase 2 (VRK2) is an anti-apoptotic Ser/Thr kinase that enhances drug sensitivity in cancer cells. This protein exists in two isoforms: VRK2A, the longer variant, and VRK2B, which lacks the C-terminal region and transmembrane domain. While the therapeutic importance of VRK2 family proteins is known, the specific roles of VRK2A and its interplay with apoptotic regulator Bcl-xL (B-cell lymphoma-extra Large) remain elusive. Bcl-xL regulates cell death by interacting with BAX (B-cell lymphoma-2 Associated X-protein), controlling its cellular localization and influencing BAX-associated processes and signalling pathways...
November 9, 2023: Biochemical Journal
https://read.qxmd.com/read/37905668/loss-of-the-methylarginine-reader-function-of-snd1-confers-resistance-to-hepatocellular-carcinoma
#40
JOURNAL ARTICLE
Tanner Wright, Yalong Wang, Sabrina A Stratton, Manu Sebastian, Bin Liu, David G Johnson, Mark T Bedford
Staphylococcal nuclease Tudor domain containing 1 (SND1) protein is an oncogene that "reads" methylarginine marks through its Tudor domain. Specifically, it recognizes methylation marks deposited by protein arginine methyltransferase 5 (PRMT5), which is also known to promote tumorigenesis. Although SND1 can drive hepatocellular carcinoma (HCC), it is unclear whether the SND1 Tudor domain is needed to promote HCC. We sought to identify the biological role of the SND1 Tudor domain in normal and tumorigenic settings by developing two genetically engineered SND1 mouse models, an Snd1 knockout (Snd1 KO) and an Snd1 Tudor domain-mutated (Snd1 KI) mouse, whose mutant SND1 can no longer recognize PRMT5-catalyzed methylarginine marks...
October 31, 2023: Biochemical Journal
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