journal
https://read.qxmd.com/read/38992440/bl-918-activates-pink1-parkin-signaling-pathway-to-ameliorate-the-progression-of-parkinson-s-disease
#21
JOURNAL ARTICLE
Yi Wang, Siyuan Luo, Huili Su, Zhimeng Wang, Ling Chu, Conggang Zhang
The pathogenesis of Parkinson's disease (PD) has been associated with mitochondrial dysfunction. Given that the PINK1/Parkin pathway governs mitochondrial quality control by inducing mitophagy to remove damaged mitochondria, therapeutic approaches to activate PINK1/Parkin-mediated mitophagy have the potential in the treatment of PD. Here, we have identified a new small molecule, BL-918, as an inducer of mitophagy via activating the PINK1/Parkin pathway. BL-918 triggers PINK1 accumulation and Parkin mitochondrial translocation to initiate PINK1/Parkin-mediated mitophagy...
July 9, 2024: Journal of Biological Chemistry
https://read.qxmd.com/read/38992439/an-e3-ubiquitin-ligase-localization-screen-uncovers-dtx2-as-a-novel-adp-ribosylation-dependent-regulator-of-dna-double-strand-break-repair
#22
JOURNAL ARTICLE
Billel Djerir, Isabelle Marois, Jean-Christophe Dubois, Steven Findlay, Théo Morin, Issam Senoussi, Laurent Cappadocia, Alexandre Orthwein, Alexandre Maréchal
DNA double-strand breaks (DSBs) elicit an elaborate response to signal damage and trigger repair via two major pathways: non-homologous end-joining (NHEJ), which functions throughout the interphase, and homologous recombination (HR), restricted to S/G2 phases. The DNA damage response (DDR) relies, on post-translational modifications of nuclear factors to coordinate the mending of breaks. Ubiquitylation of histones and chromatin-associated factors regulates DSB repair and numerous E3 ubiquitin ligases are involved in this process...
July 9, 2024: Journal of Biological Chemistry
https://read.qxmd.com/read/38992438/eta-secretase-like-processing-of-the-amyloid-precursor-protein-app-by-the-rhomboid-protease-rhbdl4
#23
JOURNAL ARTICLE
Ylauna Christine Megane Penalva, Sandra Paschkowsky, Sherilyn Junelle Recinto, Anthony Duchesne, Thomas Hammond, Pascal Spiegler, Gregor Jansen, Clemence Levet, François Charron, Matthew Freeman, R Anne McKinney, Jean-Francois Trempe, Lisa Marie Munter
The amyloid precursor protein (APP) is a key protein in Alzheimer's disease synthesized in the endoplasmic reticulum (ER) and translocated to the plasma membrane where it undergoes proteolytic cleavages by several proteases. Conversely to other known proteases, we previously elucidated rhomboid protease RHBDL4 as a novel APP processing enzyme where several cleavages likely occur already in the ER. Interestingly, the pattern of RHBDL4-derived large APP C-terminal fragments resemble those generated by the η-secretase or MT5-MMP, which was described to generate so called Aη fragments...
July 9, 2024: Journal of Biological Chemistry
https://read.qxmd.com/read/38992437/in-fanconi-anemia-impaired-accumulation-of-bone-marrow-neutrophils-during-emergency-granulopoiesis-induces-hematopoietic-stem-cell-stress
#24
JOURNAL ARTICLE
Liping Hu, Weiqi Huang, Bin Liu, Elizabeth A Eklund
Fanconi Anemia (FA) is an inherited disorder of DNA-repair due to mutation in one of 20+ interrelated genes that repair intra-strand DNA crosslinks and rescue collapsed or stalled replication forks. The most common hematologic abnormality in FA is anemia, but progression to bone marrow failure (BMF), clonal hematopoiesis, or acute myeloid leukemia (AML) may also occur. In prior studies, we found that Fanconi DNA-repair is required for successful emergency granulopoiesis; the process for rapid neutrophil production during the innate immune response...
July 9, 2024: Journal of Biological Chemistry
https://read.qxmd.com/read/38992436/activation-of-nemo-like-kinase-in-diamond-blackfan-anemia-suppresses-early-erythropoiesis-by-preventing-mitochondrial-biogenesis
#25
JOURNAL ARTICLE
Mark C Wilkes, Aya Shibuya, Y Lucy Liu, Kailen Mark, Jaqueline Mercado, Mallika Saxena, Ryan S Sathianathen, Hye Na Kim, Bertil Glader, Paraic Kenny, Kathleen M Sakamoto
Diamond Blackfan Anemia (DBA) is a rare macrocytic red blood cell aplasia that usually presents within the first year of life. The vast majority of patients carry a mutation in one of approximately 20 genes that results in ribosomal insufficiency with the most significant clinical manifestations being anemia and a predisposition to cancers. Nemo-like Kinase (NLK) is hyperactivated in the erythroid progenitors of DBA patients and inhibition of this kinase improves erythropoiesis, but how NLK contributes to the pathogenesis of the disease is unknown...
July 9, 2024: Journal of Biological Chemistry
https://read.qxmd.com/read/38992435/substitution-of-2-oxoglutarate-alters-reaction-outcomes-of-the-pseudomonas-savastanoi-ethylene-forming-enzyme
#26
JOURNAL ARTICLE
Siddhant Dhingra, Zhihong Zhang, Christopher T Lohans, Lennart Brewitz, Christopher J Schofield
In seeding plants, biosynthesis of the phytohormone ethylene, which regulates processes including fruit ripening and senescence, is catalyzed by 1-aminocyclopropyl-1-carboxylic acid (ACC) oxidase. The plant pathogen Pseudomonas savastanoi (previously classified as: P. syringae) employs a different type of ethylene-forming enzyme (psEFE), though from the same structural superfamily as ACC oxidase, to catalyze ethylene formation from 2-oxoglutarate (2OG) in an arginine dependent manner. psEFE also catalyzes the more typical oxidation of arginine to give L-Δ1 -pyrroline-5-carboxylate (P5C), a reaction coupled to oxidative decarboxylation of 2OG giving succinate and CO2 ...
July 9, 2024: Journal of Biological Chemistry
https://read.qxmd.com/read/38992434/regulatable-assembly-of-synthetic-microtubule-architectures-using-engineered-microtubule-associated-protein-idr-condensates
#27
JOURNAL ARTICLE
Chih-Chia Chang, Scott M Coyle
Microtubule filaments are assembled into higher-order structures using microtubule-associated proteins (MAPs). However, synthetic MAPs that direct the formation of new structures are challenging to design, as nanoscale biochemical activities must be organized across micron length-scales. Here we develop modular MAP-IDR condensates (synMAPs) that enable inducible assembly of higher-order microtubule structures for synthetic exploration in vitro and in mammalian cells. synMAPs harness a small microtubule-binding domain from oligodendrocytes (TPPP) whose activity we show can be rewired by interaction with unrelated condensate-forming IDR sequences...
July 9, 2024: Journal of Biological Chemistry
https://read.qxmd.com/read/38981533/the-lipid-droplet-assembly-complex-consists-of-seipin-and-four-accessory-factors-in-budding-yeast
#28
JOURNAL ARTICLE
Chao-Wen Wang, Rey-Huei Chen, Yu-Kai Chen
Seipin, a crucial protein for cellular lipid droplet (LD) assembly, oligomerizes at the interface between the endoplasmic reticulum (ER) and LDs to facilitate neutral lipid packaging. Using proximity labeling, we identify four proteins-Ldo45, Ldo16, Tgl4, and Pln1-that are recruited to the vicinity of yeast seipin, the Sei1-Ldb16 complex, exclusively when seipin function is intact, hence termed seipin accessory factors. Localization studies identify Tgl4 at the ER-LD contact site, in contrast to Ldo45, Ldo16 and Pln1 at the LD surface...
July 7, 2024: Journal of Biological Chemistry
https://read.qxmd.com/read/38970886/correction-calsyntenin-3-interacts-with-both-%C3%AE-and-%C3%AE-neurexins-in-the-regulation-of-excitatory-synaptic-innervation-in-specific-schaffer-collateral-pathways
#29
Hyeonho Kim, Dongwook Kim, Jinhu Kim, Hee-Yoon Lee, Dongseok Park, Hyeyeon Kang, Keiko Matsuda, Fredrik H Sterky, Michisuke Yuzaki, Jin Young Kim, Se-Young Choi, Jaewon Ko, Ji Won Um
No abstract text is available yet for this article.
July 5, 2024: Journal of Biological Chemistry
https://read.qxmd.com/read/38971317/transport-of-protein-disulfide-isomerase-from-the-endoplasmic-reticulum-to-the-extracellular-space-without-passage-through-the-golgi-complex
#30
JOURNAL ARTICLE
Percillia Victoria Santos Oliveira, Marco Dalla Torre, Victor Debbas, Andrea Orsi, Francisco Rafael Martins Laurindo, Roberto Sitia
Protein disulfide isomerase-A1 (PDIA1) is a master regulator of oxidative protein folding and proteostasis in the endoplasmic reticulum (ER). However, PDIA1 can reach the extracellular space, impacting thrombosis and other pathophysiological phenomena. Whether PDIA1 is externalized via passive release or active secretion is not known. To investigate how PDIA1 negotiates its export, we generated a tagged variant that undergoes N-glycosylation in the ER (Glyco-PDIA1). Addition of N- glycans does not alter its enzymatic functions...
July 4, 2024: Journal of Biological Chemistry
https://read.qxmd.com/read/38971316/characterization-of-ribosome-stalling-and-no-go-mrna-decay-stimulated-by-the-fragile-x-protein-fmrp
#31
JOURNAL ARTICLE
MaKenzie R Scarpitti, Benjamin Pastore, Wen Tang, Michael G Kearse
Loss of functional fragile X mental retardation protein (FMRP) causes fragile X syndrome (FXS) and is the leading monogenic cause of autism spectrum disorders and intellectual disability. FMRP is most notably a translational repressor and is thought to inhibit translation elongation by stalling ribosomes as FMRP-bound polyribosomes from brain tissue are resistant to puromycin and nuclease treatment. Here, we present data showing that the C-terminal non-canonical RNA-binding domain of FMRP is essential and sufficient to induce puromycin-resistant mRNA•ribosome complexes...
July 4, 2024: Journal of Biological Chemistry
https://read.qxmd.com/read/38971315/exogenous-serpin-b1-restricts-immune-complex-mediated-net-formation-via-inhibition-of-a-chymotrypsin-like-protease-and-enhances-microbial-phagocytosis
#32
JOURNAL ARTICLE
Ting Wang, Arpit Rathee, Philip A Pemberton, Christian Lood
Immune complex (IC)-driven formation of neutrophil extracellular traps (NETs) is a major contributing factor to the pathogenesis of autoimmune diseases including systemic lupus erythematosus (SLE). Exogenous recombinant human serpin B1 (rhsB1) can regulate NET formation however, it's mechanism(s) of action are currently unknown as is its ability to regulate IC-mediated NET formation and other neutrophil effector functions. To investigate this, we engineered or post-translationally modified rhsB1 proteins that possessed specific neutrophil protease inhibitory activities and pretreated isolated neutrophils with them prior to inducing NET formation with ICs derived from patients with SLE, PMA or the calcium ionophore A23187...
July 4, 2024: Journal of Biological Chemistry
https://read.qxmd.com/read/38971314/polyglutamine-binding-protein-1-regulates-neurite-outgrowth-through-recruiting-n-wasp
#33
JOURNAL ARTICLE
Xuejiao Huang, Shanshan Cheng, Junhai Han
Neurite outgrowth is a critical step in neural development, leading to the generation of neurite branches that allow individual neurons to make contacts with multiple neurons within the target region. Polyglutamine-binding protein 1 (PQBP1) is a highly conserved protein with a key role in neural development. Our recent mass spectrometric analysis showed that PQBP1 associates with neural Wiskott-Aldrich syndrome protein (N-WASP), an important actin polymerization-promoting factor involved in neurite outgrowth...
July 4, 2024: Journal of Biological Chemistry
https://read.qxmd.com/read/38971313/e41k-mutation-activates-bruton-s-tyrosine-kinase-by-stabilizing-an-inositol-hexakisphosphate-dependent-invisible-dimer
#34
JOURNAL ARTICLE
Subhankar Chowdhury, Manas Pratim Chakraborty, Swarnendu Roy, Bipra Prasad Dey, Kaustav Gangopadhyay, Rahul Das
Bruton's tyrosine kinase (BTK) regulates diverse cellular signaling of the innate and adaptive immune system in response to microbial pathogens. Downregulation or constitutive activation of BTK is reported in patients with autoimmune diseases or various B-cell leukemias. BTK is a multidomain protein tyrosine kinase that adopts an Src-like autoinhibited conformation maintained by the interaction between the kinase and PH-TH domains. The PH-TH domain plays a central role in regulating BTK function. BTK is activated by binding to PIP3 at the plasma membrane upon stimulation by the B-cell receptor (BCR)...
July 4, 2024: Journal of Biological Chemistry
https://read.qxmd.com/read/38971312/torc2-is-required-for-accumulation-of-%C3%AE-h2a-in-response-to-dna-damage
#35
JOURNAL ARTICLE
Adiel Cohen, Lea Lubenski, Ava Mouzon, Martin Kupiec, Ronit Weisman
TOR protein kinases serve as the catalytic subunit of the TORC1 and TORC2 complexes, which regulate cellular growth, proliferation and survival. In the fission yeast, Schizosaccharomyces pombe, cells lacking TORC2 or its downstream kinase Gad8 (AKT or SGK1 in human cells) exhibit sensitivity to a wide range of stress conditions, including DNA damage stress. One of the first responses to DNA damage is the phosphorylation of C-terminal serine residues within histone H2AX in human cells (γH2AX), or histone H2A in yeast cells (γH2A)...
July 4, 2024: Journal of Biological Chemistry
https://read.qxmd.com/read/38971311/conserved-and-repetitive-motifs-in-an-intrinsically-disordered-protein-drive-%C3%A2-%C2%BA-carboxysome-assembly
#36
JOURNAL ARTICLE
Julia B Turnsek, Luke M Oltrogge, David F Savage
All cyanobacteria and some chemoautotrophic bacteria fix CO2 into sugars using specialized proteinaceous compartments called carboxysomes. Carboxysomes enclose the enzymes Rubisco and carbonic anhydrase inside a layer of shell proteins to increase the CO2 concentration for efficient carbon fixation by Rubisco. In the ⍺-carboxysome lineage, a disordered and highly repetitive protein named CsoS2 is essential for carboxysome formation and function. Without it, the bacteria require high CO2 to grow. How does a protein predicted to be lacking structure serve as the architectural scaffold for such a vital cellular compartment? In this study, we identify key residues present in the repeats of CsoS2, VTG and Y, which are necessary for building functional ⍺-carboxysomes in vivo...
July 4, 2024: Journal of Biological Chemistry
https://read.qxmd.com/read/38971310/mgst3-regulates-bace1-protein-translation-and-amyloidogenesis-by-controlling-the-rgs4-mediated-akt-signaling-pathway
#37
JOURNAL ARTICLE
Yalan Pu, Jie Yang, Qiulin Pan, Chenlu Li, Lu Wang, Xiaoyong Xie, Xue Chen, Fei Xiao, Guojun Chen
Microsomal glutathione transferase 3 (MGST3) regulates eicosanoid and glutathione metabolism. These processes are associated with oxidative stress and apoptosis, suggesting that MGST3 might play a role in the pathophysiology of Alzheimer's disease (AD). Here, we report that knockdown (KD) of MGST3 in cell lines reduced the protein level of beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) and the resulting amyloidogenesis. Interestingly, MGST3 KD did not alter intracellular ROS level but selectively reduced the expression of apoptosis indicators which could be associated with the receptor of cysteinyl leukotrienes (cysLTs), the downstream metabolites of MGST3 in arachidonic acid pathway...
July 4, 2024: Journal of Biological Chemistry
https://read.qxmd.com/read/38971309/myosin-1c-differentially-displaces-tropomyosin-isoforms-altering-their-inhibition-of-motility
#38
JOURNAL ARTICLE
Luther W Pollard, Malgorzata Boczkowska, Roberto Dominguez, E Michael Ostap
Force generation and motility by actomyosin in non-muscle cells are spatially regulated by ∼40 tropomyosin (Tpm) isoforms. The means by which Tpms are targeted to specific cellular regions and the mechanisms that result in differential activity of myosin paralogs are unknown. We show that Tpm3.1 and Tpm1.7 inhibit Myosin-IC (Myo1C), with Tpm1.7 more effectively reducing the number of gliding filaments compared to Tpm3.1. Strikingly, cosedimentation and fluorescence microscopy assays revealed that Tpm3...
July 4, 2024: Journal of Biological Chemistry
https://read.qxmd.com/read/38971308/residues-in-the-fructose-binding-pocket-are-required-for-ketohexokinase-a-activity
#39
JOURNAL ARTICLE
Juliana C Ferreira, Adrian J Villanueva, Samar Fadl, Kenana Al Adem, Zeynep Nur Cinviz, Lyudmila Nedyalkova, Thyago H S Cardoso, Mario Edson Andrade, Nitin K Saksena, Ozge Sensoy, Wael M Rabeh
Excessive fructose consumption is a primary contributor to the global surges in obesity, cancer, and metabolic syndrome. Fructolysis is not robustly regulated and is initiated by ketohexokinase (KHK). In this study, we determined the crystal structure of KHK-A, one of two human isozymes of KHK, in the apo-state at 1.85 Å resolution, and we investigated the roles of residues in the fructose-binding pocket by mutational analysis. Introducing alanine at D15, N42, or N45 inactivated KHK-A, whereas mutating R141 or K174 reduced activity and thermodynamic stability...
July 4, 2024: Journal of Biological Chemistry
https://read.qxmd.com/read/38969063/elucidating-regulation-of-polyhydroxyalkanoate-metabolism-in-r-eutropha-identification-of-transcriptional-regulators-from-phasin-and-depolymerase-genes
#40
JOURNAL ARTICLE
Lara Santolin, Rosalie Sandra Josianne Eichenroth, Paul Cornehl, Henrike Wortmann, Christian Forbrig, Anne Schulze, Inam Ul Haq, Sabine Brantl, Juri Rappsilber, Sebastian Lothar Riedel, Peter Neubauer, Matthias Gimpel
Despite the ever-growing research interest in polyhydroxyalkanoates (PHAs) as green plastic alternatives, our understanding of the regulatory mechanisms governing PHA synthesis, storage, and degradation in the model organism Ralstonia eutropha remains limited. Given its importance for central carbon metabolism, PHA homeostasis is probably controlled by a complex network of transcriptional regulators. Understanding this fine-tuning is key for developing improved PHA production strains thereby boosting the application of PHAs...
July 3, 2024: Journal of Biological Chemistry
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