journal
https://read.qxmd.com/read/37247757/regulation-of-cgas-and-sting-signaling-during-inflammation-and-infection
#21
REVIEW
Samuel D Chauvin, W Alexander Stinson, Derek J Platt, Subhajit Poddar, Jonathan J Miner
Stimulator of interferon genes (STING) is a sensor of cyclic dinucleotides including cyclic GMP-AMP (cGAMP), which is produced by cGAMP synthase (cGAS) in response to cytosolic DNA. The cGAS-STING signaling pathway regulates both innate and adaptive immune responses, as well as fundamental cellular functions such as autophagy, senescence, and apoptosis. Mutations leading to constitutive activation of STING cause devastating human diseases. Thus, the cGAS-STING pathway is of great interest because of its role in diverse cellular processes and because of the potential therapeutic implications of targeting cGAS and STING...
May 27, 2023: Journal of Biological Chemistry
https://read.qxmd.com/read/37247756/nore1-inhibits-age-associated-myeloid-lineage-skewing-and-clonal-hematopoiesis-but-facilitates-termination-of-emergency-stress-granulopoiesis
#22
JOURNAL ARTICLE
Olatundun Williams, Liping Hu, Weiqi Huang, Priyam Patel, Elizabeth T Bartom, Ling Bei, Elizabeth Hjort, Christina Hijiya, Elizabeth A Eklund
Age-associated bone marrow changes include myeloid skewing and mutations that lead to clonal hematopoiesis. Molecular mechanisms for these events are ill-defined, but decreased expression of Irf8/Icsbp (interferon regulatory factor 8/interferon consensus sequence binding protein) in aging hematopoietic stem cells (HSCs) may contribute. Irf8 functions as a leukemia suppressor for chronic myeloid leukemia (CML), and young Irf8-/- mice have neutrophilia with progression to acute myeloid leukemia (AML) with aging...
May 27, 2023: Journal of Biological Chemistry
https://read.qxmd.com/read/37245780/structural-basis-for-water-modulating-rna-duplex-formation-in-the-cug-repeats-of-myotonic-dystrophy-type-1
#23
JOURNAL ARTICLE
Shun-Ching Wang, Yi-Tsao Chen, Roshan Satange, Jhih-Wei Chu, Ming-Hon Hou
Secondary structures formed by expanded CUG RNA are involved in the pathobiology of myotonic dystrophy type 1. Understanding the molecular basis of toxic RNA structures can provide insights into the mechanism of disease pathogenesis and accelerate the drug discovery process. Here, we report the crystal structure of CUG repeat RNA containing three U-U mismatches between C-G and G-C base pairs. The CUG RNA crystallizes as an A-form duplex, with the first and third U-U mismatches adopting a water-mediated asymmetric mirror isoform geometry...
May 26, 2023: Journal of Biological Chemistry
https://read.qxmd.com/read/37236359/the-stathmin-2-membrane-targeting-domain-is-required-for-axon-protection-and-regulated-degradation-by-dlk-signaling
#24
JOURNAL ARTICLE
Emma J C Thornburg-Suresh, Jerianne E Richardson, Daniel W Summers
Axon integrity is essential for functional connectivity in the nervous system. The degeneration of stressed or damaged axons is a common and sometimes initiating event in neurodegenerative disorders. Stathmin-2 (Stmn2) is an axon maintenance factor that is depleted in Amyotrophic Lateral Sclerosis, and replenishment of Stmn2 can restore neurite outgrowth in diseased neurons. However, mechanisms responsible for Stmn2-mediated axon maintenance in injured neurons are not known. We used primary sensory neurons to interrogate the role of Stmn2 in the degeneration of severed axons...
May 24, 2023: Journal of Biological Chemistry
https://read.qxmd.com/read/37236358/lysophosphatidylglycerol-lpg-phospholipase-d-maintains-membrane-homeostasis-in-staphylococcus-aureus-by-converting-lpg-to-lysophosphatidic-acid
#25
JOURNAL ARTICLE
Chitra Subramanian, Mi-Kyung Yun, Matthew M Frank, Charles O Rock
Lysophospholipids are deacylated derivatives of their bilayer forming phospholipid counterparts that are present at low concentrations in cells. Phosphatidylglycerol (PG) is the principal membrane phospholipid in Staphylococcus aureus and lysophosphatidylglycerol (LPG) is detected in low abundance. Here, we used a mass spectrometry screen to identify locus SAUSA300_1020 as the gene responsible for maintaining low concentrations of 1-acyl-LPG in S. aureus. The SAUSA300_1020 gene encodes a protein with a predicted amino terminal transmembrane α-helix attached to a globular glycerophosphodiester phosphodiesterase (GDPD) domain...
May 24, 2023: Journal of Biological Chemistry
https://read.qxmd.com/read/37236357/%C3%AE-igh-resolution-structure-of-mammalian-pi31-20s-proteasome-complex-reveals-mechanism-of-proteasome-inhibition
#26
JOURNAL ARTICLE
Hao-Chi Hsu, Jason Wang, Abbey Kjellgren, Huilin Li, George N DeMartino
Proteasome-catalyzed protein degradation mediates and regulates critical aspects of many cellular functions and is an important element of proteostasis in health and disease. Proteasome function is determined in part by the types of proteasome holoenzymes formed between the 20S core particle that catalyzes peptide bond hydrolysis and any of multiple regulatory proteins to which it binds. One of these regulators, PI31, was previously identified as an in vitro 20S proteasome inhibitor, but neither the molecular mechanism nor the possible physiologic significance of PI31-mediated proteasome inhibition has been clear...
May 24, 2023: Journal of Biological Chemistry
https://read.qxmd.com/read/37236356/the-cilia-and-flagella-associated-protein-cfap52-orchestrated-with-cfap45-is-required-for-sperm-motility-in-mice
#27
JOURNAL ARTICLE
Bingbing Wu, Rachel Li, Shuang Ma, Yanjie Ma, Lijun Fan, Chunxiu Gong, Chao Liu, Ling Sun, Li Yuan
Asthenozoospermia characterized by decreased sperm motility is a major cause of male infertility, but the majority of their etiology remains unknown. Here, we showed that the cilia and flagella associated protein 52 (Cfap52) gene was predominantly expressed in testis and its deletion in a Cfap52 knockout mouse model resulted in decreased sperm motility and male infertility. Cfap52 knockout also led to the disorganization of midpiece-principal piece junction of the sperm tail, but had no effect on the axoneme ultrastructure in spermatozoa...
May 24, 2023: Journal of Biological Chemistry
https://read.qxmd.com/read/37236355/structure-of-complex-iii-with-bound-antimalarial-agent-ck-2-68-provides-insights-into-selective-inhibition-of-plasmodium-cytochrome-bc-1-complexes
#28
JOURNAL ARTICLE
Lothar Esser, Fei Zhou, Allison Zeher, Weimin Wu, Rick Huang, Chang-An Yu, Kristin D Lane, Thomas E Wellems, Di Xia
Among the various components of the protozoan Plasmodium mitochondrial respiratory chain, only Complex III is a validated cellular target for antimalarial drugs. The compound CK-2-68 was developed to specifically target the alternate NADH dehydrogenase of the malaria parasite respiratory chain, but the true target for its antimalarial activity has been controversial. Here, we report the cryo-EM structure of mammalian mitochondrial Complex III bound with CK-2-68 and examine the structure-function relationships of the inhibitor's selective action on Plasmodium...
May 24, 2023: Journal of Biological Chemistry
https://read.qxmd.com/read/37230389/mutational-and-biophysical-analyses-reveal-a-tfiiic-binding-region-in-the-tfiif-related-rpc53-subunit-of-rna-polymerase-iii
#29
JOURNAL ARTICLE
Arvind Chandra Shekhar, Wen-Jin Wu, Hung-Ta Chen
The TFIIF-like Rpc53/Rpc37 heterodimer of RNA polymerase (pol) III is involved in various stages of transcription. The C-terminal region of Rpc53 dimerizes with Rpc37 to anchor on the lobe domain of the pol III cleft. However, structural and functional features of the Rpc53 N-terminal region had not been characterized previously. Here, we conducted site-directed alanine replacement mutagenesis on the Rpc53 N-terminus, generating yeast strains that exhibited a cold-sensitive growth defect and severely compromised pol III transcriptional activity...
May 23, 2023: Journal of Biological Chemistry
https://read.qxmd.com/read/37230388/the-deubiquitinase-usp28-maintains-the-expression-of-the-transcription-factor-mycn-and-is-essential-in-neuroblastoma-cells
#30
JOURNAL ARTICLE
Junjun Li, Jin Peng, Lingzhi Wu, Xiang Shen, Xinghua Zhen, Yimao Zhang, Huailu Ma, Yongfeng Xu, Qunli Xiong, Qing Zhu, Pumin Zhang
Neuroblastoma (NB) is one of the most common extracranial solid tumors in children. MYCN gene amplification is highly associated with poor prognosis in high-risk neuroblastoma patients. In non-MYCN-amplified high-risk NB patients, the expression of c-MYC (MYCC) and its target genes is highly elevated. USP28 as a deubiquitinase is known to regulate the stability of MYCC. We show here USP28 also regulates the stability of MYCN. Genetic depletion or pharmacologic inhibition of the deubiquitinase strongly destabilizes MYCN and stops the growth of neuroblastoma cells that overexpress MYCN...
May 23, 2023: Journal of Biological Chemistry
https://read.qxmd.com/read/37230387/identification-of-inhibitors-for-the-trans-membrane-trypanosoma-cruzi-eif2%C3%AE-kinase-relevant-for-parasite-proliferation
#31
JOURNAL ARTICLE
Tiago de Paula Marcelino, Angela Maria Fala, Matheus Monteiro da Silva, Normanda Souza-Melo, Amaranta Muniz Malvezzi, Angélica Hollunder Klippel, Martin Zoltner, Norma Padilla-Mejia, Samantha Kosto, Mark C Field, Gabriela de Assis Burle Caldas, Santuza Maria Ribeiro Teixeira, Rafael Miguez Couñago, Katlin Brauer Massirer, Sergio Schenkman
The TcK2 protein kinase of Trypanosoma cruzi, the causative agent of Chagas disease, is structurally similar to the human kinase PERK, which phosphorylates the initiation factor eIF2α, and in turn, inhibits translation initiation. We have previously shown that absence of TcK2 kinase impairs parasite proliferation within mammalian cells, positioning it as a potential target for treatment of Chagas disease. To better understand its role in the parasite, here we initially confirmed the importance of TcK2 in parasite proliferation by generating CRISPR/Cas9 TcK2-null cells, albeit more efficiently differentiate into infective forms...
May 23, 2023: Journal of Biological Chemistry
https://read.qxmd.com/read/37224964/wssi-from-the-gram-negative-bacterial-cellulose-synthase-is-an-o-acetyltransferase-that-acts-on-cello-oligomers-with-several-acetyl-donor-substrates
#32
JOURNAL ARTICLE
Alysha J N Burnett, Emily Rodriguez, Shirley Constable, Brian Lowrance, Michael Fish, Joel T Weadge
In microbial biofilms, bacterial cells are encased in a self-produced matrix of polymers (e.g., exopolysaccharides) that enable surface adherence and protect against environmental stressors. For example, the wrinkly spreader phenotype of Pseudomonas fluorescens colonizes food/water sources and human tissue to form robust biofilms that can spread across surfaces. This biofilm largely consists of bacterial cellulose produced by the cellulose synthase proteins encoded by the wss operon, which also occurs in other species, including pathogenic Achromobacter species...
May 22, 2023: Journal of Biological Chemistry
https://read.qxmd.com/read/37224963/mistranslation-of-the-genetic-code-by-a-new-family-of-bacterial-transfer-rnas
#33
JOURNAL ARTICLE
Dominik B Schuntermann, Jonathan T Fischer, Jonmatthew Bile, Sarah A Gaier, Brett A Shelley, Aya Awawdeh, Martina Jahn, Kyle S Hoffman, Eric Westhof, Dieter Söll, Christopher R Clarke, Oscar Vargas-Rodriguez
The correct coupling of amino acids with transfer RNAs (tRNAs) is vital for translating genetic information into functional proteins. Errors during this process lead to mistranslation, where a codon is translated using the wrong amino acid. While unregulated and prolonged mistranslation is often toxic, growing evidence suggests that organisms, from bacteria to humans, can induce and use mistranslation as a mechanism to overcome unfavorable environmental conditions. Most known cases of mistranslation are caused by translation factors with poor substrate specificity or when substrate discrimination is sensitive to molecular changes such as mutations or post-translational modifications...
May 22, 2023: Journal of Biological Chemistry
https://read.qxmd.com/read/37224962/the-u1-antisense-morpholino-oligonucleotide-amo-disrupts-u1-snrnp-structure-to-promote-intronic-pcpa-modification-of-pre-mrnas
#34
JOURNAL ARTICLE
Qiumin Feng, Zejin Lin, Yanhui Deng, Yi Ran, Rui Yu, Andy Peng Xiang, Congting Ye, Chengguo Yao
Functional depletion of the U1 small nuclear ribonucleoprotein (snRNP) with a 25 nt U1 AMO (antisense morpholino oligonucleotide) may lead to intronic premature cleavage and polyadenylation (PCPA) of thousands of genes, a phenomenon known as U1 snRNP telescripting; however, the underlying mechanism remains elusive. In this study, we demonstrated that U1 AMO could disrupt U1 snRNP structure both in vitro and in vivo, thereby affecting the U1 snRNP/RNAP polymerase II (RNAPII) interaction. By performing ChIP-seq for phosphorylation of Ser2 (Ser2P) and Ser5 (Ser5P) of the C-terminal domain (CTD) of RPB1, the largest subunit of RNAPII, we showed that transcription elongation was disturbed upon U1 AMO treatment, with a particular high Ser2P signal at intronic cryptic polyadenylation sites (PASs)...
May 22, 2023: Journal of Biological Chemistry
https://read.qxmd.com/read/37224961/molecular-basis-and-dual-ligand-regulation-of-tetrameric-estrogen-receptor-%C3%AE-14-3-3%C3%AE-protein-complex
#35
JOURNAL ARTICLE
Bente A Somsen, Eline Sijbesma, Seppe Leysen, Karolina Honzejkova, Emira J Visser, Peter J Cossar, Tomáš Obšil, Luc Brunsveld, Christian Ottmann
Therapeutic strategies targeting Nuclear Receptors (NRs) beyond their endogenous ligand binding pocket have gained significant scientific interest, driven by a need to circumvent problems associated with drug resistance and pharmacological profile. The hub protein 14-3-3 is an endogenous regulator of various NRs, providing a novel entry point for small molecule modulation of NR activity. Exemplified, 14-3-3 binding to the C-terminal F-domain of the Estrogen Receptor alpha (ERα), and small molecule stabilization of the ERα/14-3-3ζ protein complex by the natural product Fusicoccin A (FC-A), was demonstrated to downregulate ERα-mediated breast cancer proliferation...
May 22, 2023: Journal of Biological Chemistry
https://read.qxmd.com/read/37220856/domains-required-for-the-interaction-of-the-central-negative-element-frq-with-its-transcriptional-activator-wcc-within-the-core-circadian-clock-of-neurospora
#36
JOURNAL ARTICLE
Bin Wang, Jay C Dunlap
In the negative feedback loop composing the Neurospora circadian clock, the core element, FREQUENCY (FRQ) binds with FRH (FRQ-interacting RNA helicase) and Casein Kinase 1 (CK1) to form the FRQ-FRH complex (FFC) which represses its own expression by interacting with and promoting phosphorylation of its transcriptional activators White Collar-1 (WC-1) and WC-2 (together forming the White Collar Complex, WCC). Physical interaction between FFC and WCC is a prerequisite for the repressive phosphorylations, and although the motif on WCC needed for this interaction is known, the reciprocal recognition motif(s) on FRQ remains poorly defined...
May 21, 2023: Journal of Biological Chemistry
https://read.qxmd.com/read/37220855/actin-binding-protein-filamin-b-regulates-the-cell-surface-retention-of-endothelial-sphingosine-1-phosphate-receptor-1
#37
JOURNAL ARTICLE
Xian Zhao, Keisuke Kiyozuka, Akimitsu Konishi, Reika Kawabata-Iwakawa, Yoji Andrew Minamishima, Hideru Obinata
Sphingosine 1-phosphate receptor 1 (S1PR1) is a G protein-coupled receptor essential for vascular development and postnatal vascular homeostasis. When exposed to sphingosine 1-phosphate (S1P) in the blood of ∼1 μM, S1PR1 in endothelial cells retains cell-surface localization, while lymphocyte S1PR1 shows almost complete internalization, suggesting the cell-surface retention of S1PR1 is endothelial cell-specific. To identify regulating factors that function to retain S1PR1 on the endothelial cell surface, here we utilized an enzyme-catalyzed proximity labeling technique followed by proteomic analyses...
May 21, 2023: Journal of Biological Chemistry
https://read.qxmd.com/read/37220854/rapid-reaction-kinetics-of-the-butyryl-coa-dehydrogenase-component-of-the-electron-bifurcating-crotonyl-coa-dependent-nadh-ferredoxin-oxidoreductase-from-megasphaera-elsdenii
#38
JOURNAL ARTICLE
Wayne Vigil, Derek Nguyen, Dimitri Niks, Russ Hille
We have investigated the equilibrium properties and rapid-reaction kinetics of the isolated butyryl-CoA dehydrogenase (bcd) component of the electron-bifurcating crotonyl-CoA-dependent NADH:ferredoxin oxidoreductase (EtfAB:bcd) from Megasphaera elsdenii. We find that a neutral FADH• semiquinone accumulates transiently during both reduction with sodium dithionite and with NADH in the presence of catalytic concentrations of EtfAB. In both cases full reduction of bcd to the hydroquinone is eventually observed, but the accumulation of FADH• indicates that a substantial portion of reduction occurs in sequential one-electron processes rather than a single two-electron event...
May 21, 2023: Journal of Biological Chemistry
https://read.qxmd.com/read/37217003/lpgat1-lplat7-regulates-acyl-chain-profiles-at-the-sn-1-position-of-phospholipids-in-murine-skeletal-muscles
#39
JOURNAL ARTICLE
Tomoki Sato, Shuhei Umebayashi, Nanami Senoo, Takumi Akahori, Hiyori Ichida, Noriyuki Miyoshi, Takuya Yoshida, Yuki Sugiura, Naoko Goto-Inoue, Hiroki Kawana, Hideo Shindou, Takashi Baba, Yuki Maemoto, Yasutomi Kamei, Takao Shimizu, Junken Aoki, Shinji Miura
Skeletal muscle consists of both fast- and slow-twitch fibers. Phospholipids are important structural components of cellular membranes, and the diversity of their fatty acid composition affects membrane fluidity and permeability. Although some studies have shown that acyl chain species in phospholipids differ among various muscle fiber types, the mechanisms underlying these differences are unclear. To investigate this, we analyzed phosphatidylcholine (PC) and phosphatidylethanolamine (PE) molecules in the murine extensor digitorum longus (EDL; fast-twitch) and soleus (slow-twitch) muscles...
May 20, 2023: Journal of Biological Chemistry
https://read.qxmd.com/read/37211093/control-of-atypical-pkc%C3%AE-membrane-dissociation-by-tyrosine-phosphorylation-within-a-pb1-c1-interdomain-interface
#40
JOURNAL ARTICLE
Mathias Cobbaut, Neil Q McDonald, Peter J Parker
Atypical PKCs are cell polarity kinases that operate at the plasma membrane where they function within multiple molecular complexes to contribute to the establishment and maintenance of polarity. In contrast to the classical and novel PKCs, atypical PKCs do not respond to diacylglycerol cues to bind the membrane compartment. Until recently it was not clear how aPKCs are recruited; whether aPKCs can directly interact with membranes or whether they are dependent on other protein interactors to do so. Two recent studies identified the pseudo-substrate region and the C1 domain as direct membrane interaction modules, however their relative importance and coupling are unknown...
May 19, 2023: Journal of Biological Chemistry
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