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Ligand-induced assembly of antibody variable fragments for the chemical regulation of biological processes Cell Chem. Bio. (IF 6.6) Pub Date : 2025-02-13 Erik Rihtar, Tina Fink, Tina Lebar, Duško Lainšček, Živa Kolenc, Lucija Kadunc Polajnar, Roman Jerala
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Lifetime of ground conformational state determines the activity of structured RNA Nat. Chem. Biol. (IF 12.9) Pub Date : 2025-02-12 Rhese D. Thompson, Derek L. Carbaugh, Joshua R. Nielsen, Ciara M. Witt, Edgar M. Faison, Rita M. Meganck, Atul Rangadurai, Bo Zhao, Jeffrey P. Bonin, Nathan I. Nicely, William F. Marzluff, Aaron T. Frank, Helen M. Lazear, Qi Zhang
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Pharmacodynamics of Akt drugs revealed by a kinase-modulated bioluminescent indicator Nat. Chem. Biol. (IF 12.9) Pub Date : 2025-02-11 Yan Wu, Chenzhou Hao, Chao Gao, Matt Hageman, Sungmoo Lee, Thomas A. Kirkland, Nathanael S. Gray, Yichi Su, Michael Z. Lin
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Gains in early-onset dementia with progranulin open new paths for drug discovery Nat. Biotechnol. (IF 33.1) Pub Date : 2025-02-11
The first clinical results in patients with a genetic form of frontotemporal dementia (FTD) show that enhancing progranulin in the brain may halt disease progression. If successful, this potentially disease-modifying approach may uncover new avenues for treating other neurodegenerative diseases.
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Precise RNA targeting with CRISPR–Cas13d Nat. Biotechnol. (IF 33.1) Pub Date : 2025-02-11 Sydney K. Hart, Simon Müller, Hans-Hermann Wessels, Alejandro Méndez-Mancilla, Gediminas Drabavicius, Olivia Choi, Neville E. Sanjana
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Poldip2 promotes mtDNA elimination during Drosophila spermatogenesis to ensure maternal inheritance. EMBO J. (IF 9.4) Pub Date : 2025-02-11 Ziming Wang,Tirawit Meerod,Nuria Cortes-Silva,Ason C-Y Chiang,Ziyan Nie,Ying Di,Peiqiang Mu,Ankit Verma,Adam James Reid,Hansong Ma
Maternal inheritance of mitochondrial DNA (mtDNA) is highly conserved in metazoans. While many species eliminate paternal mtDNA during late sperm development to foster maternal inheritance, the regulatory mechanisms governing this process remain elusive. Through a forward genetic screen in Drosophila, we identified 47 mutant lines exhibiting substantial retention of mtDNA in mature sperm. We mapped
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Pharmacological CDK4/6 inhibition promotes vulnerability to lysosomotropic agents in breast cancer. EMBO J. (IF 9.4) Pub Date : 2025-02-10 Jamil Nehme,Sjors Maassen,Sara Bravaccini,Michele Zanoni,Caterina Gianni,Ugo De Giorgi,Abel Soto-Gamez,Abdullah Altulea,Teodora Gheorghe,Boshi Wang,Marco Demaria
Breast cancer is a leading cause of mortality worldwide. Pharmacological inhibitors of cyclin-dependent kinases (CDK) 4 and 6 (CDK4/6i) inhibit breast cancer growth by inducing a senescent-like state. However, the long-term treatment efficacy remains limited by the development of drug resistance, so clearance of senescent-like cancer cells may extend the durability of treatment. However, we show here
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Organoid modeling reveals the tumorigenic potential of the alveolar progenitor cell state. EMBO J. (IF 9.4) Pub Date : 2025-02-10 Jingyun Li,Susanna M Dang,Shreoshi Sengupta,Paul Schurmann,Antonella F M Dost,Aaron L Moye,Maria F Trovero,Sidrah Ahmed,Margherita Paschini,Preetida J Bhetariya,Roderick Bronson,Shannan J Ho Sui,Carla F Kim
Cancers display cellular, genetic and epigenetic heterogeneity, complicating disease modeling. Multiple cell states defined by gene expression have been described in lung adenocarcinoma (LUAD). However, the functional contributions of cell state and the regulatory programs that control chromatin and gene expression in the early stages of tumor initiation are not well understood. Using single-cell RNA
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Emerging Approaches to Investigating Functional Protein Dynamics in Modular Redox Enzymes: Nitric Oxide Synthase as a Model System. J. Biol. Chem. (IF 4.0) Pub Date : 2025-02-08 Ting Jiang,Megan C Thielges,Changjian Feng
Approximately 80% of eukaryotic and 65% of prokaryotic proteins are composed of multiple folding units (i.e., domains) connected by flexible linkers. These dynamic protein architectures, facilitated by linker regions, support essential functions such as electron transfer, respiration, and biosynthesis. This review critically assesses recent advancements in methods for studying protein dynamics, with
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Differential producibility analysis reveals drug-associated carbon and nitrogen metabolite expressions in Mycobacterium tuberculosis. J. Biol. Chem. (IF 4.0) Pub Date : 2025-02-08 Ye Xu,Ruma Banerjee,Sunitha Kasibhatla,Rajendra Joshi,Khushboo Borah Slater
Mycobacterium tuberculosis (Mtb) is one of the world's successful pathogens that flexibly adapts its metabolic nature during infection of the host, and in response to drugs. Here we used genome scale metabolic modelling coupled with differential producibility analysis (DPA) to translate RNA seq datasets into metabolite signals and identified drug-associated metabolic response profiles. We tested four
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De novo designed Hsp70 activator dissolves intracellular condensates Cell Chem. Bio. (IF 6.6) Pub Date : 2025-02-07 Jason Z. Zhang, Nathan Greenwood, Jason Hernandez, Josh T. Cuperus, Buwei Huang, Bryan D. Ryder, Christine Queitsch, Jason E. Gestwicki, David Baker
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Expanding the molecular grammar of polar residues and arginine in FUS phase separation Nat. Chem. Biol. (IF 12.9) Pub Date : 2025-02-07 Noah Wake, Shuo-Lin Weng, Tongyin Zheng, Szu-Huan Wang, Valentin Kirilenko, Jeetain Mittal, Nicolas L. Fawzi
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Arginine: at the crossroads of nitrogen metabolism. EMBO J. (IF 9.4) Pub Date : 2025-02-07 Tak Shun Fung,Keun Woo Ryu,Craig B Thompson
L-arginine is the most nitrogen-rich amino acid, acting as a key precursor for the synthesis of nitrogen-containing metabolites and an essential intermediate in the clearance of excess nitrogen. Arginine's side chain possesses a guanidino group which has unique biochemical properties, and plays a primary role in nitrogen excretion (urea), cellular signaling (nitric oxide) and energy buffering (phosphocreatine)
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Mutations in the kinesin KIF12 promote MASH in humans and mice by disrupting lipogenic enzyme turnover. EMBO J. (IF 9.4) Pub Date : 2025-02-07 Asieh Etemad,Yosuke Tanaka,Shuo Wang,Mordechai Slae,Mutaz Sultan,Orly Elpeleg,Nobutaka Hirokawa
As a common cause of liver cirrhosis, metabolic dysfunction-associated steatohepatitis (MASH) is regarded as a target of therapeutic intervention. However, a successful therapy has not yet been found, partly because the molecular pathogenesis is largely elusive. Here we show that KIF12 kinesin suppresses MASH development by accelerating the breakdown of two lipid biosynthesis enzymes, acetyl-CoA carboxylase
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Mechanistic insights into inactivating mutations in the proton-coupled folate transporter (SLC46A1), and compensatory mutations that restore function. J. Biol. Chem. (IF 4.0) Pub Date : 2025-02-07 Prithviraj Nandigrami,I David Goldman,Andras Fiser
Hereditary folate malabsorption (HFM) is a rare, autosomal recessive disorder characterized by impaired intestinal absorption and impaired transport of folates across the choroid plexus into cerebral spinal fluid due to inactivating mutations in the hPCFT gene, which encodes the proton-coupled folate transporter (PCFT-SLC46A1). Understanding the structural impact of these mutations is crucial for elucidating
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Persistent activation of TRPM4 triggers necrotic cell death characterized by sodium overload Nat. Chem. Biol. (IF 12.9) Pub Date : 2025-02-06 Wan Fu, Jianghuang Wang, Tianyu Li, Yuhui Qiao, Zili Zhang, Xiaomin Zhang, Mingkai He, Yan Su, Ziye Zhao, Chen Li, Ronghua Xiao, Yujun Han, Shen Zhang, Zhiqiang Liu, James Lin, Guoqiang Chen, Yang Li, Qing Zhong
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Structure of a mutated photosystem II complex reveals changes to the hydrogen-bonding network that affect proton egress during O-O bond formation. J. Biol. Chem. (IF 4.0) Pub Date : 2025-02-06 David A Flesher,Jieun Shin,Richard J Debus,Gary W Brudvig
Photosystem II (PSII) is the water-splitting enzyme of oxygenic photosynthesis. Using light energy, PSII catalytically oxidizes two water molecules to fuel downstream metabolism, forming an O-O bond and releasing O2 as a byproduct. The reaction mechanism requires the strategic removal of four protons via conserved hydrogen-bonding networks, but these pathways remain poorly understood. Site-directed
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Biochemical and biophysical characterization of inositol-tetrakisphosphate 1-kinase inhibitors. J. Biol. Chem. (IF 4.0) Pub Date : 2025-02-06 Martin Y Ng,Huanchen Wang,Haibo Zhang,Isabel Prucker,Lalith Perera,Ekaterina Goncharova,Antony Wamiru,Henning J Jessen,Robin E Stanley,Stephen B Shears,Ji Luo,Barry R O'Keefe,Brice A P Wilson
Inositol phosphates (IPs) and inositol pyrophosphate play critical roles in many biological processes as signaling molecules in pathways responsible for cellular functions involved in growth and maintenance. The biosynthesis of IPs is carried out by a family of inositol phosphate kinases. In mammals, Inositol tetrakisphosphate kinase-1 (ITPK1) phosphorylates inositol-1,3,4-trisphosphate (Ins(1,3,4)P3)
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Metformin inhibits the histone methyltransferase CARM1 and attenuates H3 histone methylation during gluconeogenesis. J. Biol. Chem. (IF 4.0) Pub Date : 2025-02-06 Sinjini Dhang,Atanu Mondal,Chandrima Das,Siddhartha Roy
Hyperglycemia is a hallmark of metabolic disorders, yet the precise mechanisms linking epigenetic regulation to glucose metabolism remain underexplored. Coactivator-associated arginine methyltransferase 1 (CARM1), a type I histone methyltransferase, promotes transcriptional activation through the methylation of histone H3 at arginine residues H3R17 and H3R26. Here, we identify a novel mechanism by
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Taste receptor type 1 member 3 in osteoclasts regulates osteoclastogenesis via detection of glucose. J. Biol. Chem. (IF 4.0) Pub Date : 2025-02-06 Anna Yoshimura,Takuma Matsubara,Nao Kodama,Yoshimitsu Kakuta,Kazuma Yasuda,Ryusuke Yoshida,Osamu Kaminuma,Shuhei Hosomi,Hiroji Shinkawa,Quan Yuan,Tatsuo Kawamoto,Shoichiro Kokabu
The taste system extends beyond the oral cavity, with various taste receptors found in extraoral organs. Mice deficient in the taste receptor type 1 (TAS1R) family member, TAS1R3, and fed a high-fat, high-sugar diet showed high bone mass without altering food consumption. However, the underlying mechanisms, including the cell types responsible for TAS1R3 expression, remain unclear. Here, we demonstrate
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Dentin sialoprotein acts as an angiogenic factor through association with the membrane receptor endoglin. J. Biol. Chem. (IF 4.0) Pub Date : 2025-02-06 Ximin Xu,Jing Fu,Guobin Yang,Zhi Chen,Shuo Chen,Guohua Yuan
Dentin sialophosphoprotein (DSPP) is highly expressed by odontoblasts, the cell type responsible for dentin formation. DSPP therefore has been extensively studied as a regulator of dentinogenesis. Besides defective dentinogenesis in teeth, Dspp deficient mice also display reduced blood vessels in the transition zone of femurs. However, the exact role and underlying mechanisms of DSPP in the process
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Knocking out p38α+p38β+p38γ is required to abort the myogenic program in C2C12 myoblasts and to impose uncontrolled proliferation. J. Biol. Chem. (IF 4.0) Pub Date : 2025-02-06 Navit Mooshayef,Nechama Gilad,Manju P Mohanam,David Engelberg
The p38 MAPKs' family includes four isoforms, of which only p38α has been considered essential for numerous important processes including mice embryogenesis. It is also considered essential for myoblast to myotube differentiation, as exposure of myoblasts to p38α/β inhibitors or to siRNA that targets p38α suppresses the process. The functions of p38β and p38γ in myoblast differentiation are not clear
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Complement-activated fragment Ba functions as an antibacterial protein and mediates immune responses in lower vertebrates. J. Biol. Chem. (IF 4.0) Pub Date : 2025-02-06 Xiao-Yan Jin,Hong-Qiang Zhang,Zhe Feng,Heng Liu,Xuan-Yue Wang,Hao-Bin Luo,Xue-Peng Li,Yuan-Yuan Sun,Mo-Fei Li
The complement system plays an important role in antibacterial infection and immune regulation. Ba, an important complement component, is produced and released by the cleavage of complement factor B (CFB) during complement activation. However, the immune functions of Ba are unclear. In this study, we reported that recombinant Ba exerted direct bactericidal and immune regulatory effects. Recombinant
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RNA G-Quadruplexes regulate mammalian mirtron biogenesis. J. Biol. Chem. (IF 4.0) Pub Date : 2025-02-06 Uzma Salim,Manoj B Menon,Sonam Dhamija,Perumal Vivekanandan
Mirtrons are the predominant class of non-canonical miRNAs derived from introns through a Drosha-independent, splicing-dependent pathway. Unregulated splicing of introns containing hairpins may adversely impact Dicer/Ago-mediated canonical miRNA biogenesis. However, the mechanism regulating mirtron biogenesis remains poorly understood. We found that the 5' arm of plant mirtrons and invertebrate mirtrons
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Programming biological communication between distinct membraneless compartments Nat. Chem. Biol. (IF 12.9) Pub Date : 2025-02-05 Bo-Tao Ji, He-Tong Pan, Zhi-Gang Qian, Xiao-Xia Xia
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SEED-Selection enables high-efficiency enrichment of primary T cells edited at multiple loci Nat. Biotechnol. (IF 33.1) Pub Date : 2025-02-05 Christopher R. Chang, Vivasvan S. Vykunta, Jae Hyun J. Lee, Ke Li, Clara Kochendoerfer, Joseph J. Muldoon, Charlotte H. Wang, Thomas Mazumder, Yang Sun, Daniel B. Goodman, William A. Nyberg, Chang Liu, Vincent Allain, Allison Rothrock, Chun J. Ye, Alexander Marson, Brian R. Shy, Justin Eyquem
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Safer non-viral DNA delivery using lipid nanoparticles loaded with endogenous anti-inflammatory lipids Nat. Biotechnol. (IF 33.1) Pub Date : 2025-02-05 Manthan N. Patel, Sachchidanand Tiwari, Yufei Wang, Sarah O’Neill, Jichuan Wu, Serena Omo-Lamai, Carolann Espy, Liam S. Chase, Aparajeeta Majumder, Evan Hoffman, Anit Shah, András Sárközy, Jeremy Katzen, Norbert Pardi, Jacob S. Brenner
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Sound healing and beyond Nat. Biotechnol. (IF 33.1) Pub Date : 2025-02-04
Ultrasound neurotechnologies are moving quickly into clinical trials in a wide variety of applications, and initiatives to open-source their manufacture will make them more accessible.
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Implantation of engineered adipocytes suppresses tumor progression in cancer models Nat. Biotechnol. (IF 33.1) Pub Date : 2025-02-04 Hai P. Nguyen, Kelly An, Yusuke Ito, Bhushan N. Kharbikar, Rory Sheng, Breanna Paredes, Elizabeth Murray, Kimberly Pham, Michael Bruck, Xujia Zhou, Cassandra Biellak, Aki Ushiki, Mai Nobuhara, Sarah L. Fong, Daniel A. Bernards, Filipa Lynce, Deborah A. Dillon, Mark Jesus M. Magbanua, Laura A. Huppert, Heinz Hammerlindl, Jace Anton Klein, Luis Valdiviez, Oliver Fiehn, Laura Esserman, Tejal A. Desai
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Quantifying metabolites using structure-switching aptamers coupled to DNA sequencing Nat. Biotechnol. (IF 33.1) Pub Date : 2025-02-04 June H. Tan, Andrew G. Fraser
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REPLACE-ing RNA through evolution Nat. Chem. Biol. (IF 12.9) Pub Date : 2025-02-04 Christopher E. Denes, G. Gregory Neely
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Author Correction: Multiplexed inhibition of immunosuppressive genes with Cas13d for combinatorial cancer immunotherapy Nat. Biotechnol. (IF 33.1) Pub Date : 2025-02-03 Feifei Zhang, Ryan D. Chow, Emily He, Chuanpeng Dong, Shan Xin, Daniyal Mirza, Yanzhi Feng, Xiaolong Tian, Nipun Verma, Medha Majety, Yueqi Zhang, Guangchuan Wang, Sidi Chen
Correction to: Nature Biotechnology https://doi.org/10.1038/s41587-024-02535-2, published online 16 January 2025.
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Author Correction: Bioinstructive implantable scaffolds for rapid in vivo manufacture and release of CAR-T cells Nat. Biotechnol. (IF 33.1) Pub Date : 2025-02-03 Pritha Agarwalla, Edikan A. Ogunnaike, Sarah Ahn, Kristen A. Froehlich, Anton Jansson, Frances S. Ligler, Gianpietro Dotti, Yevgeny Brudno
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THE REGULATION OF CELL METABOLISM BY HYPOXIA AND HYPERCAPNIA. J. Biol. Chem. (IF 4.0) Pub Date : 2025-02-04 Ben Reddan,Eoin P Cummins
Every cell in the body is exposed to a certain level of CO2 and O2. Hypercapnia and hypoxia elicit stress signals to influence cellular metabolism and function. Both conditions exert profound yet distinct effects on metabolic pathways and mitochondrial dynamics, highlighting the need for cells to adapt to changes in the gaseous microenvironment. The interplay between hypercapnia and hypoxia signalling
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An oral tricyclic STING agonist suppresses tumor growth through remodeling of the immune microenvironment Cell Chem. Bio. (IF 6.6) Pub Date : 2025-02-03 Hong-Yi Zhao, Zhongwei Liu, Jinsong Tao, Shuai Mao, Meilin Wang, Miao He, Bo Wen, Wei Gao, Duxin Sun
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AnimalGWASAtlas: annotation and prioritization of GWAS loci and quantitative trait loci for animal complex traits. J. Biol. Chem. (IF 4.0) Pub Date : 2025-02-03 Yuwei Gou,Yunhan Jing,Yifei Wang,Xingyu Li,Jing Yang,Kai Wang,Hengdong He,Yuan Yang,Yuanling Tang,Chen Wang,Jun Xu,Fan Yang,Mingzhou Li,Qianzi Tang
Genome-wide association study (GWAS) and quantitative trait locus (QTL) mapping methods provide valuable insights and opportunities for identifying functional gene underlying phenotype formation. However, the majority of GWAS risk loci and QTLs located in non-coding regions, posing significant challenges in pinpointing the protein-coding genes associated with specific traits. Moreover, growing evidence
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Tetraspanin CD9 alters cellular trafficking and endocytosis of tetraspanin CD63, affecting CD63 packaging into small extracellular vesicles. J. Biol. Chem. (IF 4.0) Pub Date : 2025-02-03 Leanne C Duke,Allaura S Cone,Li Sun,Dirk P Dittmer,David G Meckes,Robert J Tomko
Small extracellular vesicles (sEVs) are particles secreted from cells that play vital roles both in normal physiology and in human disease. sEVs are highly enriched in tetraspanin proteins, such as CD9 and CD63, and contain tetraspanin-enriched membrane microdomains involved in loading of sEVs with macromolecule cargoes and in sEV biogenesis. However, the precise roles of individual tetraspanins in
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MIA40 circumvents the folding constraints imposed by TRIAP1 function. J. Biol. Chem. (IF 4.0) Pub Date : 2025-02-03 Jordi Pujols,Marc Fornt,Marcos Gil-García,Andrea Bartolomé-Nafría,Francesc Canals,Linda Cerofolini,Kaare Teilum,Lucia Banci,Sebastián A Esperante,Salvador Ventura
The MIA40 relay system mediates the import of small cysteine-rich proteins into the intermembrane mitochondrial space (IMS). MIA40 substrates are synthesized in the cytosol and assumed to be disordered in their reduced state in this compartment. As they cross the outer mitochondrial membrane, MIA40 promotes the oxidation of critical native disulfides to facilitate folding, trapping functional species
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Phosphodiesterase 5 expression in photoreceptors rescues retinal degeneration induced by deregulation of membrane guanylyl cyclase. J. Biol. Chem. (IF 4.0) Pub Date : 2025-02-03 Alexander M Dizhoor,Shinya Sato,Zhuokai Luo,Lyuqi Tan,Fay E Levin,Elena V Olshevskaya,Igor V Peshenko,Vladimir J Kefalov
Mutations in retinal membrane guanylyl cyclase 1 (RetGC1) and its calcium-sensor protein (GCAP1) cause congenital dominant retinopathies by elevation of cGMP synthesis in photoreceptors in the dark. We explored counteracting the elevated cGMP synthesis causing photoreceptor degeneration using ectopic expression of a non-photoreceptor cGMP phosphodiesterase (PDE) isozyme PDE5. PDE5 primary structure
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O-GlcNAc modification differentially regulates microtubule binding and pathological conformations of tau isoforms in vitro. J. Biol. Chem. (IF 4.0) Pub Date : 2025-02-03 Mohammed M Alhadidy,Paul M Stemmer,Nicholas M Kanaan
Tau proteins undergo several post-translational modifications (PTMs) in physiological and disease conditions. In Alzheimer's disease, O-linked β-d-N-acetylglucosamine (O-GlcNAcylation) modification of serine/threonine (S/T) residues in tau is reduced. In mouse models of tauopathy, O-GlcNAcase inhibitors lead to increased O-GlcNAcylation and decreased filamentous aggregates of tau. However, various
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Regulation of respiratory syncytial virus nucleoprotein oligomerization by phosphorylation. J. Biol. Chem. (IF 4.0) Pub Date : 2025-02-03 Vincent Basse,Yao Wang,Carine Rodrigues-Machado,Céline Henry,Charles-Adrien Richard,Cédric Leyrat,Marie Galloux
The negative-sense RNA genome of respiratory syncytial virus (RSV) is encapsidated by the viral nucleoprotein N, forming a left-handed helical nucleocapsid which serves as template for the viral polymerase. Specific oligomerization of N along the viral genome necessitates a switch of conformation of N, from the neosynthesized monomeric and RNA-free N protein, named N0, to N-RNA oligomers. Although
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Sodium Proton Exchanger NHE9 pHine-Tunes Exosome Production by Impairing Rab7 Activity. J. Biol. Chem. (IF 4.0) Pub Date : 2025-02-03 Mariam Duhaini,Perla Fares,Lili Hafezi,Hadi El-Zein,Kalyan C Kondapalli
Cell-to-cell communication is mediated by vesicles ranging from 30 to 150 nanometers, known as exosomes. These exosomes shuttle bioactive molecules such as proteins, lipids, and nucleic acids, thus playing crucial roles in both health and disease mechanisms. Exosomes form within the endocytic pathway through the process of inward budding of the endosomal membrane, facilitated by the progressive acidification
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Modulation of the Substrate Preference of a MYST Acetyltransferase by a Scaffold Protein. J. Biol. Chem. (IF 4.0) Pub Date : 2025-02-03 Raghuvir N Sengupta,Oleg Brodsky,Patrick Bingham,Wade C Diehl,RoseAnn Ferre,Samantha E Greasley,Eric Johnson,Michelle Kraus,Whitney Lieberman,Jordan L Meier,Thomas A Paul,Karen A Maegley
The MYST family of lysine acetyltransferases are transcriptional regulators often dysregulated in cancer. In cells, MYST members form distinct multiprotein complexes that guide their histone substrate specificity, but how this selectivity is conferred is not fully understood. Here we interrogate a complex-mediated change in the substrate preference of the MYST member KAT6A, a target for cancer therapeutics
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Aggregated proinsulin in pancreatic β-cells is degraded by the autophagy pathway. J. Biol. Chem. (IF 4.0) Pub Date : 2025-02-03 Yueh-Fu Madey,Samreen K Syed,Robert Daniel Van Horn,Annie R Pineros,Alexander M Efanov
Insulin, a critical metabolic hormone to maintain blood glucose homeostasis, is synthesized and folded in the endoplasmic reticulum (ER) of pancreatic β-cells as the insulin precursor proinsulin. Proinsulin misfolding and aggregation detected in diabetic β-cells induces ER stress and obstructs normal trafficking, processing, and secretion of insulin, which eventually can result in pancreatic β-cell
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Drug resistance-associated mutations in Plasmodium UBP-1 disrupt its essential deubiquitinating activity. J. Biol. Chem. (IF 4.0) Pub Date : 2025-02-03 Cameron J Smith,Heledd Eavis,Carla Briggs,Ryan Henrici,Maryia Karpiyevich,Megan R Ansbro,Johanna Hoshizaki,Gerbrand J van der Heden van Noort,David B Ascher,Colin J Sutherland,Marcus C S Lee,Katerina Artavanis-Tsakonas
Deubiquitinating enzymes function to cleave ubiquitin moieties from modified proteins, serving to maintain the pool of free ubiquitin in the cell while simultaneously impacting the fate and function of a target protein. Like all eukaryotes, Plasmodium parasites rely on the dynamic addition and removal of ubiquitin for their own growth and survival. While humans possess around 100 DUBs, Plasmodium contains
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Transmembrane Parkinson's Disease mutation of PINK1 leads to altered mitochondrial anchoring. J. Biol. Chem. (IF 4.0) Pub Date : 2025-02-03 Raelynn Brassard,Elena Arutyunova,Emmanuella Takyi,L Michel Espinoza-Fonseca,Howard Young,Nicolas Touret,M Joanne Lemieux
Parkinson's disease (PD) is a devastating neurodegenerative disease resulting from the death of dopaminergic neurons in the substantia nigra pars compacta of the midbrain. Familial and sporadic forms of the disease have been linked to mitochondrial dysfunction. Pathology has been identified with mutations in the PARK6 gene encoding PTEN-induced kinase 1 (PINK1), a quality control protein in the mitochondria
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Phosphorylation of distal C-terminal residues promotes TRPV4 channel activation in response to arachidonic acid. J. Biol. Chem. (IF 4.0) Pub Date : 2025-02-03 Aravind Parthasarathy,Andriy Anishkin,Yangjing Xie,Kostiantyn Drachuk,Yoshinori Nishijma,Juan Fang,Sevasti B Koukouritaki,David A Wilcox,David X Zhang
Transient receptor potential vanilloid 4 (TRPV4) is a Ca2+-permeable channel activated by diverse physical and chemical stimuli, including mechanical stress and endogenous lipid arachidonic acid (AA) and its metabolites. Phosphorylation of TRPV4 by protein kinase A (PKA) and protein kinase C (PKC) is a predominant mechanism for channel regulation, especially in the cytoplasmic domains due to their
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Kinetics insight into the roles of the N- and C-lobes of calmodulin in RyR1 channel regulation. J. Biol. Chem. (IF 4.0) Pub Date : 2025-02-02 Jingyan Zhang,Levy M Treinen,Skylar J Mast,Megan R McCarthy,Bengt Svensson,David D Thomas,Razvan L Cornea
Calmodulin (CaM) activates the skeletal muscle Ca2+ release channel (ryanodine receptor, RyR1) at nanomolar Ca2+ and inhibits it at micromolar Ca2+. CaM conversion from RyR1 activator to inhibitor is due to structural changes induced by Ca2+ binding at CaM's two lobes. However, it remains unclear which lobe provides the switch for this conversion. Here, we attached the environment-sensitive fluorophore
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Harmine promotes axon regeneration through enhancing glucose metabolism. J. Biol. Chem. (IF 4.0) Pub Date : 2025-02-02 Ruixuan Liu,Bing Zhou
Axon regeneration requires a substantial mitochondrial energy supply. However, injured mature neurons often fail to regenerate due to their inability to meet these elevated energy demands. Our findings indicate that harmine compensates for the energy deficit following axonal injury by enhancing the coupling between glucose metabolism and mitochondrial homeostasis, thereby promoting axon regeneration
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Author Correction: An extrinsic motor directs chromatin loop formation by cohesin. EMBO J. (IF 9.4) Pub Date : 2025-01-31 Thomas M Guérin,Christopher Barrington,Georgii Pobegalov,Maxim I Molodtsov,Frank Uhlmann
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Telomerase RNA evolution: a journey from plant telomeres to broader eukaryotic diversity. Biochem. J. (IF 4.4) Pub Date : 2025-01-31 Petr Fajkus,Jiří Fajkus
Telomeres, essential for maintaining genomic stability, are typically preserved through the action of telomerase, a ribonucleoprotein complex that synthesizes telomeric DNA. One of its two core components, telomerase RNA (TR), serves as the template for this synthesis, and its evolution across different species is both complex and diverse. This review discusses recent advancements in understanding
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Polyamines enhance repeat-associated non-AUG translation from CCUG repeats by stabilizing the tertiary structure of RNA. J. Biol. Chem. (IF 4.0) Pub Date : 2025-01-31 Akihiro Oguro,Takeshi Uemura,Kodai Machida,Kanata Kitajiri,Ayasa Tajima,Takemitsu Furuchi,Gota Kawai,Hiroaki Imataka
Repeat expansion disorders are caused by abnormal expansion of microsatellite repeats. Repeat-associated non-AUG (RAN) translation is one of the pathogenic mechanisms underlying repeat expansion disorders, but the exact molecular mechanism underlying RAN translation remains unclear. Polyamines are ubiquitous biogenic amines that are essential for cell proliferation and cellular functions. They are
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Dehydrometabolites of siphonaxanthin, a carotenoid from green algae, suppress TLR1/2-induced inflammatory response more strongly than siphonaxanthin. J. Biol. Chem. (IF 4.0) Pub Date : 2025-01-31 Yuki Manabe,Tomoaki Nitta,Misato Ichihara,Takashi Maoka,Tatsuya Sugawara
Siphonaxanthin is a carotenoid found in green algae that exhibits potent anti-inflammatory activities. We previously reported that ingested siphonaxanthin accumulates in various organs of mice; however, its metabolic conversion remains largely unknown. In this study, we isolated three siphonaxanthin dehydrometabolites and determined their chemical structures. Two of these metabolites were obtained
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A splicing variant in EFCAB7 hinders ciliary transport and disrupts cardiac development. J. Biol. Chem. (IF 4.0) Pub Date : 2025-01-31 Xin Yang,Qiuye Wang,Tianyuan Li,Yan Zhou,Jimiao Gao,Wanting Ma,Na Zhao,Xinyue Liu,Zihe Ai,Steven Y Cheng,Yayun Gu,Bijun Zhao,Shen Yue,Zhibin Hu
The Tetralogy of Fallot (TOF), the most prevalent form of cyanotic congenital heart disease, stems from abnormal development of the outflow tract during embryogenesis. Despite the crucial role played by primary cilia in heart development, there is currently insufficient evidence to establish a causal relationship between defects in genes related to primary cilia and non-syndromic TOF. Here, we performed
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A BRAF-activated non-coding RNA attenuates clear cell renal cell carcinoma via repression of glucose-6-phosphate dehydrogenase. J. Biol. Chem. (IF 4.0) Pub Date : 2025-01-31 Wenjing Liu,Yueli Ni,Honggang Bai,Xiangjie Liu,Asif Shahzad,Kun Cui,Qiuxin Duan,Ziyuan Bai,Yurong Dong,Zihan Yi,Buqing Sai,Yingmin Kuang,Chen Guo,Yuechun Zhu,Qiao Zhang,Zhe Yang
Clear cell renal cell carcinoma (ccRCC) is a disease rooted in metabolic disorders, distinguished by abnormally high activity of glucose 6-phosphate dehydrogenase (G6PD). G6PD serves as a key rate-limiting enzyme in the pentose phosphate pathway. Meanwhile, BRAF-activated non-coding RNA (BANCR) has emerged as a crucial regulatory factor linked to various cancers. The expression pattern of BANCR varies
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Modulating the complement system through epitope-specific inhibition by complement C3 inhibitors. J. Biol. Chem. (IF 4.0) Pub Date : 2025-01-31 Zhidong Chen,Mingshuang Wang,Wenqian Duan,Yi Xia,Huiqin Liu,Feng Qian
As an integral part of the innate immune system, the complement system is a tightly regulated proteolytic cascade, playing a critical role in microbial defense, inflammation activation, and dying host cell clearance. Complement proteins are now emerging as subjects of intense research and drug development, since dysregulation of the complement system plays a critical role in several diseases and disorders
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Mechanistic insights and approaches for beta cell regeneration Nat. Chem. Biol. (IF 12.9) Pub Date : 2025-01-29 Christos Karampelias, Ka-Cheuk Liu, Anders Tengholm, Olov Andersson
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ADSL promotes autophagy and tumor growth through fumarate-mediated Beclin1 dimethylation Nat. Chem. Biol. (IF 12.9) Pub Date : 2025-01-29 Lei Wang, Runze Shi, Shuo Wang, Yuran Duan, Zheng Wang, Peixiang Zheng, Xue Sun, Xiaohan Chen, Guimei Ji, Yuli Shen, Bofei Dong, Yanni Lin, Ting Wen, Qi Tian, Zhanpeng Guo, Yueru Hou, Shiqi Wu, Ling Xiao, Min Li, Liwei Xiao, Qingang Wu, Ying Meng, Guijun Liu, Sofie Duan, Xueli Bai, Tong Liu, Zhiren Zhang, Peng Zhan, Zhimin Lu, Daqian Xu