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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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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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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
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Quinone extraction drives atmospheric carbon monoxide oxidation in bacteria Nat. Chem. Biol. (IF 12.9) Pub Date : 2025-01-29 Ashleigh Kropp, David L. Gillett, Hari Venugopal, Miguel A. Gonzálvez, James P. Lingford, Surbhi Jain, Christopher K. Barlow, Jie Zhang, Chris Greening, Rhys Grinter
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AAV vectors tested in perfused human livers Nat. Biotechnol. (IF 33.1) Pub Date : 2025-01-29 Roland W. Herzog, Ype P. de Jong
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A neural network for long-term super-resolution imaging of live cells with reliable confidence quantification Nat. Biotechnol. (IF 33.1) Pub Date : 2025-01-29 Chang Qiao, Shuran Liu, Yuwang Wang, Wencong Xu, Xiaohan Geng, Tao Jiang, Jingyu Zhang, Quan Meng, Hui Qiao, Dong Li, Qionghai Dai
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AAV capsid prioritization in normal and steatotic human livers maintained by machine perfusion Nat. Biotechnol. (IF 33.1) Pub Date : 2025-01-29 Jae-Jun Kim, Simone N. T. Kurial, Pervinder K. Choksi, Miguel Nunez, Tyler Lunow-Luke, Jan Bartel, Julia Driscoll, Chris L. Her, Simaron Dhillon, William Yue, Abhishek Murti, Tin Mao, Julian N. Ramos, Amita Tiyaboonchai, Markus Grompe, Aras N. Mattis, Shareef M. Syed, Bruce M. Wang, Jacquelyn J. Maher, Garrett R. Roll, Holger Willenbring
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Unlocking drug modes of action with multi-dimensional high-throughput metabolic profiling Nat. Biotechnol. (IF 33.1) Pub Date : 2025-01-28
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SLC25A1 and ACLY maintain cytosolic acetyl-CoA and regulate ferroptosis susceptibility via FSP1 acetylation. EMBO J. (IF 9.4) Pub Date : 2025-01-29 Wei Li,Jing Han,Bin Huang,Tengteng Xu,Yihong Wan,Dan Luo,Weiyao Kong,Ying Yu,Lei Zhang,Yong Nian,Bo Chu,Chengqian Yin
Ferroptosis, an iron-dependent form of programmed cell death characterized by excessive lipid hydroperoxides accumulation, emerges as a promising target in cancer therapy. Among the solute carrier (SLC) superfamily, the cystine/glutamate transporter system antiporter components SLC3A2 and SLC7A11 are known to regulate ferroptosis by facilitating cystine import for ferroptosis inhibition. However, the
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The C-terminal structure of the N6-methyladenosine deaminase YerA and its role in deamination. Biochem. J. (IF 4.4) Pub Date : 2025-01-29 Qian Jia,Hui Zeng,Nan Xiao,Jing Tang,Shangfang Gao,Wei Xie
The N6-methyladenine (6mA) modification is an essential epigenetic marker and plays a crucial role in processes, such as DNA repair, replication, gene expression regulation, etc. YerA from Bacillus subtilis is considered a novel class of enzymes capable of catalyzing the deamination of 6mA to produce hypoxanthine. Despite the significance of this type of enzymes in bacterial self-defense systems and
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Engineering electrogenetic interfaces for mammalian cell control Cell Chem. Bio. (IF 6.6) Pub Date : 2025-01-28 Maysam Mansouri, Martin Fussenegger
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How to build a [2Fe–2S] cluster Nat. Chem. Biol. (IF 12.9) Pub Date : 2025-01-28 Anna Moseler, Stephan Wagner, Andreas J. Meyer
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The measurement, regulation and biological activity of FAHFAs Nat. Chem. Biol. (IF 12.9) Pub Date : 2025-01-28 Dan Tan, Alan Saghatelian
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A human metabolic map of pharmacological perturbations reveals drug modes of action Nat. Biotechnol. (IF 33.1) Pub Date : 2025-01-28 Laurentz Schuhknecht, Karin Ortmayr, Jürgen Jänes, Martina Bläsi, Eleni Panoussis, Sebastian Bors, Terézia Dorčáková, Tobias Fuhrer, Pedro Beltrao, Mattia Zampieri
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Structural basis for human NKCC1 inhibition by loop diuretic drugs. EMBO J. (IF 9.4) Pub Date : 2025-01-28 Yongxiang Zhao,Pietro Vidossich,Biff Forbush,Junfeng Ma,Jesse Rinehart,Marco De Vivo,Erhu Cao
Na+-K+-Cl- cotransporters functions as an anion importers, regulating trans-epithelial chloride secretion, cell volume, and renal salt reabsorption. Loop diuretics, including furosemide, bumetanide, and torsemide, antagonize both NKCC1 and NKCC2, and are first-line medicines for the treatment of edema and hypertension. NKCC1 activation by the molecular crowding sensing WNK kinases is critical if cells
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Micropeptide hSPAR regulates glutamine levels and suppresses mammary tumor growth via a TRIM21-P27KIP1-mTOR axis. EMBO J. (IF 9.4) Pub Date : 2025-01-28 Yan Huang,Hua Lu,Yao Liu,Jiabei Wang,Qingan Xia,Xiangmin Shi,Yan Jin,Xiaolin Liang,Wei Wang,Xiaopeng Ma,Yangyi Wang,Meng Gong,Canjun Li,Chunlei Cang,Qinghua Cui,Ceshi Chen,Tao Shen,Lianxin Liu,Xiangting Wang
mTOR plays a pivotal role in cancer growth control upon amino acid response. Recently, CDK inhibitor P27KIP1 has been reported as a noncanonical inhibitor of mTOR signaling in MEFs, via unclear mechanisms. Here, we find that P27KIP1 degradation via E3 ligase TRIM21 is inhibited by human micropeptide hSPAR through its C-terminus (hSPAR-C), causing P27KIP1's cytoplasmic accumulation in breast cancer
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A genetically encoded fluorescent biosensor for visualization of acetyl-CoA in live cells Cell Chem. Bio. (IF 6.6) Pub Date : 2025-01-27 Joseph J. Smith, Taylor R. Valentino, Austin H. Ablicki, Riddhidev Banerjee, Adam R. Colligan, Debra M. Eckert, Gabrielle A. Desjardins, Katharine L. Diehl
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The ISC machinery assembles [2Fe–2S] clusters by formation and fusion of [1Fe–1S] precursors Nat. Chem. Biol. (IF 12.9) Pub Date : 2025-01-27 Sylvain Gervason, Rafal Dutkiewicz, Kristian Want, Rania Benazza, Rémi Mor-Gautier, Aneta Grabinska-Rogala, Christina Sizun, Oscar Hernandez-Alba, Sarah Cianferani, Bruno Guigliarelli, Bénédicte Burlat, Benoit D’Autréaux
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Implications of frequent hitter E3 ligases in targeted protein degradation screens Nat. Chem. Biol. (IF 12.9) Pub Date : 2025-01-27 Xiaoyu Zhang, Gabriel M. Simon, Benjamin F. Cravatt
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Plasma membrane-associated ARAF condensates fuel RAS-related cancer drug resistance Nat. Chem. Biol. (IF 12.9) Pub Date : 2025-01-27 Wen Li, Xiaoxian Shi, Caiwei Tan, Zhaodi Jiang, Mingyi Li, Zhiheng Ji, Jing Zhou, Mengxin Luo, Zuyan Fan, Zhifan Ding, Yue Fang, Jun Sun, Junjun Ding, Huasong Lu, Weirui Ma, Wei Xie, Wenjing Su
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Structural and Kinetic Characterization of an Acetoacetyl-Coenzyme A: Acetate Coenzyme A Transferase from the Extreme Thermophile Thermosipho melanesiensis. Biochem. J. (IF 4.4) Pub Date : 2025-01-27 Ryan G Bing,Greg K Buhrman,Kathryne C Ford,Christopher T Straub,Tunyaboon Laemthong,Robert B Rose,Michael Adams,Robert M Kelly
CtfAB from the extremely thermophilic bacterium, Thermosipho melanesiensis, has been used for in vivo acetone production up to 70°C. This enzyme has tentatively been identified as the rate-limiting step, due to its relatively low binding affinity for acetate. However, existing kinetic and mechanistic studies on this enzyme are insufficient to evaluate this hypothesis. Here, kinetic analysis of purified
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The common murine retroviral integration site activating Hhex marks a distal regulatory enhancer co-opted in human Early T-cell precursor leukemia. J. Biol. Chem. (IF 4.0) Pub Date : 2025-01-27 Joyce Hardwick,Javier Rodriguez-Hernaez,Giovanni Gambi,Bryan J Venters,Yan Guo,Liqi Li,Paul E Love,Neal G Copeland,Nancy A Jenkins,Dimitrios Papaioannou,Iannis Aifantis,Aristotelis Tsirigos,Mircea Ivan,Utpal P Davé
The Hhex gene encodes a transcription factor that is important for both embryonic and post-natal development, especially of hematopoietic tissues. Hhex is one of the most common sites of retroviral integration in mouse models. We found the most common integrations in AKXD (recombinant inbred strains) T-ALLs occur 57-61kb 3' of Hhex and activate Hhex gene expression. The genomic region of murine leukemia
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Integrative in silico and biochemical analyses demonstrate direct Arl3-mediated ODA16 release from the intraflagellar transport machinery. J. Biol. Chem. (IF 4.0) Pub Date : 2025-01-27 Jiaolong Wang,Rune T Kidmose,Niels Boegholm,Nevin K Zacharia,Mads B Thomsen,Anni Christensen,Tara Malik,Karl Lechtreck,Esben Lorentzen
Outer dynein arms (ODAs) are essential for ciliary motility and are preassembled in the cytoplasm before trafficking into cilia by intraflagellar transport (IFT). ODA16 is a key adaptor protein that links ODAs to the IFT machinery via a direct interaction with the IFT46 protein. However, the molecular mechanisms regulating the assembly, transport, and release of ODAs remain poorly understood. Here
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Apolipoprotein E3 and E4 isoforms exhibit differing effects in countering endotoxins. J. Biol. Chem. (IF 4.0) Pub Date : 2025-01-27 Manoj Puthia,Jan K Marzinek,Katerina Vesela,Axel Larsson,Artur Schmidtchen,Peter J Bond,Jitka Petrlova
Apolipoprotein E (APOE) is distributed across various human tissues and plays a crucial role in lipid metabolism. Recent investigations have uncovered an additional facet of APOE's functionality, revealing its role in host defense against bacterial infections. To assess the antibacterial attributes of APOE3 and APOE4, we conducted antibacterial assays using P. aeruginosa and E. coli. Exploring the
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Structural insights into 2-oxindole-forming monooxygenase MarE: Divergent architecture and substrate positioning versus tryptophan dioxygenases. J. Biol. Chem. (IF 4.0) Pub Date : 2025-01-27 Inchul Shin,Romie C Nguyen,Samuel R Montoya,Aimin Liu
MarE, a heme-dependent enzyme, catalyzes a unique 2-oxindole-forming monooxygenation reaction from tryptophan metabolites. To elucidate its enzyme-substrate interaction mode, we present the first X-ray crystal structures of MarE in complex with its prime substrate, (2S,3S)-β-methyl-L-tryptophan and cyanide at 1.89 Å resolution as well as a truncated yet catalytically active version in complex with
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The Shab family potassium channels are highly enriched at the presynaptic terminals of human neurons. J. Biol. Chem. (IF 4.0) Pub Date : 2025-01-27 Orion Benner,Charles H Karr,Astrid Quintero-Gonzalez,Michael M Tamkun,Soham Chanda
The Shab family voltage-gated K+ channels (i.e., Kv2.1, Kv2.2) are widely expressed in mammalian brain, and regulate neuronal action-potential firing. In addition to their canonical functions, the Kv2 proteins help establish direct attachments between plasma membrane (PM) and endoplasmic reticulum (ER), also known as ER-PM junctions. However, the biochemical properties and molecular organization of
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The yeast checkpoint kinase Dun1p represses transcription of RNR genes independently of catalytic activity or Rad53p during respiratory growth. J. Biol. Chem. (IF 4.0) Pub Date : 2025-01-27 Shreya Nagar,Riddhi Mehta,Pritpal Kaur,Fatema Zohra Sadia,Suprataptha Reddy,Olasubomi R Olorunnimbe,Ivana Vancurova,Ales Vancura
One of the key events in DNA damage response (DDR) is activation of checkpoint kinases leading to activation of ribonucleotide reductase (RNR) and increased synthesis of deoxyribonucleotide triphosphates (dNTPs), required for DNA repair. Among other mechanisms, the activation of dNTP synthesis is driven by derepression of genes encoding RNR subunits RNR2, RNR3, and RNR4, following checkpoint activation