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Histone methyltransferase KMT2A: Developmental regulation to oncogenic transformation. J. Biol. Chem. (IF 4.0) Pub Date : 2024-09-18 Jayme Ogino,Yali Dou
Our current understanding of epigenetic regulation is deeply rooted in the founding contributions of Dr. C. David Allis. In 2002, Allis and colleagues first characterized the lysine methyltransferase activity of the mammalian KMT2A (MLL1), a paradigm shifting discovery that brings epigenetic dysregulation into focus for many human diseases that carry KMT2A mutations. This review will discuss the current
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A novel EZH1/2 dual inhibitor inhibits GCB DLBCL through Cell Cycle Regulation and M2 Tumor-Associated Macrophage Polarization. J. Biol. Chem. (IF 4.0) Pub Date : 2024-09-18 Ran An,Zhimeng Zhang,Dongli Zhang,Yuqing Li,Yueling Lin,Hongtao Sun,Fang Xu,Manmei Li,Zhong Liu
The incidence of germinal center B-cell-like type diffuse large B-cell lymphoma (GCB DLBCL) is steadily increasing, with a known hereditary component. Although some molecular mechanisms in GCB DLBCL have been elucidated, understanding remains incomplete, limiting the effectiveness of targeted therapies. In GCB DLBCL patients, abnormally high expression of zeste homologs 2 (EZH2) is noted, and the compensatory
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Differential functional role of Orai1 variants in constitutive Ca2+ entry and calcification in luminal breast cancer cells. J. Biol. Chem. (IF 4.0) Pub Date : 2024-09-18 Alejandro Berna-Erro,Jose Javier Lopez,Isaac Jardin,Jose Sanchez-Collado,Gines M Salido,Juan A Rosado
Resting cytosolic Ca2+ concentration is tightly regulated to fine-tune Ca2+-dependent cellular functions. Luminal breast cancer cells exhibit constitutive Ca2+ entry mediated by Orai1 and the secretory pathway Ca2+-ATPase, SPCA2, which result in mammary microcalcifications that constitute a prognostic marker of mammary lesions. Two Orai1 isoforms have been identified, the full-length Orai1α, consisting
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Protein phosphatase PP2Cα S-glutathionylation regulates cell migration. J. Biol. Chem. (IF 4.0) Pub Date : 2024-09-18 Dhanushika S K Kukulage,Kusal T G Samarasinghe,Nadee N J Matarage Don,Madhu C Shivamadhu,Kyosuke Shishikura,William Schiff,Faezeh Mashhadi Ramezani,Rayavarapu Padmavathi,Megan L Matthews,Young-Hoon Ahn
Redox signaling is a fundamental mechanism that controls all major biological processes partly via protein cysteine oxidations, including S-glutathionylation. Despite over 2,000 cysteines identified to form S-glutathionylation in databases, the identification of redox cysteines functionally linked to a biological process of interest remains challenging. Here, we demonstrate a strategy combining glutathionylation
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The prodomain of bone morphogenetic protein 2 promotes dimerization and cleavage of BMP6 homodimers and BMP2/6 heterodimers. J. Biol. Chem. (IF 4.0) Pub Date : 2024-09-18 Pooja Chauhan,Yongqiang Xue,Hyung-Seok Kim,Allison L Fisher,Jodie L Babitt,Jan L Christian
Bone morphogenetic protein 2 (BMP2) and BMP6 are key regulators of systemic iron homeostasis. All BMPs are generated as inactive precursor proteins that dimerize and are cleaved to generate the bioactive ligand and inactive prodomain fragments, but nothing is known about how BMP2 or BMP6 homodimeric or heterodimeric precursor proteins are proteolytically activated. Here, we conducted in vitro cleavage
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ADAR promotes USP38 auto-deubiquitylation and stabilization in an RNA editing-independent manner in Esophageal Squamous Cell Carcinoma. J. Biol. Chem. (IF 4.0) Pub Date : 2024-09-18 Qingyong Hu,Yahui Chen,Qianru Zhou,Shanshan Deng,Wei Hou,Yong Yi,Chenghua Li,Jiancai Tang
Esophageal cancer is mainly divided into esophageal adenocarcinoma (EADC) and esophageal squamous cell carcinoma (ESCC). China is one of the high-incidence areas of esophageal cancer, of which about 90% are ESCC. The deubiquitinase USP38 has been reported to play significant roles in several biological processes, including inflammatory responses, antiviral infection, cell proliferation, migration,
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Downregulation of the m6A reader YTHDC2 upregulates exosome content in lung adenocarcinoma via inhibiting IFIT and OAS family members. J. Biol. Chem. (IF 4.0) Pub Date : 2024-09-18 Zhixin Yin,Lifang Ma,Xiaoting Tian,Qi Sun,Congcong Zhang,Yikun Wang,Yayou Miao,Xiangfei Xue,Yongjie Wang,Jiayi Wang,Xiao Zhang,Xumin Hou
N6-Methyladenosine (m6A) is the most prevalent mRNA modification. Its biological function primarily relies on its "Reader" protein, such as YTHDC2. Previous studies have shown that YTHDC2 downregulation is a pro-carcinogenic phenomenon in lung adenocarcinoma (LUAD). However, further investigation is needed to understand the molecular mechanisms of downstream genes and the associated biological phenomena
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The N-acetylglucosaminyltransferase Radical Fringe contributes to defects in JAG1-dependent turnover and signaling of NOTCH3 CADASIL mutants. J. Biol. Chem. (IF 4.0) Pub Date : 2024-09-18 Shodai Suzuki,Taiki Mashiko,Yohei Tsukamoto,Miyu Oya,Yuki Kotani,Saki Okawara,Takemi Matsumoto,Yuki Mizue,Hideyuki Takeuchi,Tetsuya Okajima,Motoyuki Itoh
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a genetic vascular dementia characterized by age-related degeneration of vascular mural cells and accumulation of a NOTCH3 mutant protein. NOTCH3 functions as a signaling receptor, activating downstream gene expression in response to ligands like JAG1 and DLL4, which regulate the development and
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SENP3 mediates the deSUMOylation and degradation of YAP1 to regulate the progression of triple-negative breast cancer. J. Biol. Chem. (IF 4.0) Pub Date : 2024-09-11 Xu Chen,Danqing Li,Qi Su,Xing Ling,Yanyan Yang,Yuhang Liu,Xinjie Zhu,Anqi He,Siyu Ding,Runxiao Xu,Zhaoxia Liu,Xiaojun Long,Jinping Zhang,Zhihui Yang,Yitao Qi,Hongmei Wu
Triple-negative breast cancer (TNBC) is a prevalent malignancy in women, casting a formidable shadow on their well-being. Positioned within the nucleolus, SUMO-specific protease 3 (SENP3) assumes a pivotal role in the realms of development and tumorigenesis. However, the participation of SENP3 in TNBC remains a mystery. Here, we elucidate that SENP3 exerts inhibitory effects on migration and invasion
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USP11 deubiquitinates E-cadherin and maintains luminal fate of mammary tumor cells to suppress breast cancer. J. Biol. Chem. (IF 4.0) Pub Date : 2024-09-11 Tao Qian,Feng Bai,Shiwen Zhang,Yuping Xu,Yuchan Wang,Shuping Yuan,Xiong Liu,Yaru Du,Bin Peng,Wei-Guo Zhu,Xingzhi Xu,Xin-Hai Pei
Basal-like breast cancer may originate from luminal epithelial or cancerous cells. Inadequately repaired DNA damage impairs luminal differentiation and promotes aberrant luminal to basal trans-differentiation in mammary epithelial cells (MECs). Ubiquitin-specific peptidase 11 (USP11), a deubiquitinase, plays a critical role in DNA damage repair. The role of USP11 in controlling mammary cell differentiation
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Evolutionary and molecular basis of ADP-ribosylation reversal by zinc-dependent macrodomains. J. Biol. Chem. (IF 4.0) Pub Date : 2024-09-11 Antonio Ariza,Qiang Liu,Nathan Cowieson,Ivan Ahel,Dmitri V Filippov,Johannes Gregor Matthias Rack
Dynamic ADP-ribosylation signalling is a crucial pathway that controls fundamental cellular processes, in particular, the response to cellular stresses such as DNA damage, reactive oxygen species and infection. In some pathogenic microbes the response to oxidative stress is controlled by a SirTM/zinc-containing macrodomain (Zn-Macro) pair responsible for establishment and removal of the modification
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Three classes of propofol binding sites on GABAA receptors. J. Biol. Chem. (IF 4.0) Pub Date : 2024-09-11 Zi-Wei Chen,Satyanarayana M Chintala,John Bracamontes,Yusuke Sugasawa,Spencer R Pierce,Balazs R Varga,Edward H Smith,Christopher J Edge,Nicholas P Franks,Wayland Wl Cheng,Gustav Akk,Alex S Evers
Propofol is a widely used anesthetic and sedative that acts as a positive allosteric modulator (PAM) of gamma-aminobutyric acid type A (GABAA) receptors. Several potential propofol binding sites that may mediate this effect have been identified using propofol-analogue photoaffinity labeling. o-PD labels β-H267, a pore-lining residue, whereas AziPm labels residues β-M286, β-M227 and α-I239 in the two
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LAT1 supports mitotic progression through Golgi unlinking in an amino acid transport activity-independent manner. J. Biol. Chem. (IF 4.0) Pub Date : 2024-09-11 Sakura Yanagida,Ryuzaburo Yuki,Youhei Saito,Yuji Nakayama
Amino acid transporters play a vital role in cellular homeostasis by maintaining protein synthesis. L-type amino acid transporter 1 (LAT1/SLC7A5/CD98lc) is a major transporter of large neutral amino acids in cancer cells because of its predominant expression. Although amino acid restriction with various amino acid analog treatments is known to induce mitotic defects, the involvement of amino acid transporters
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New targets and designed inhibitors of ASAP Arf-GAPs derived from structural characterization of the ASAP1/440-kD ankyrin-B interaction. J. Biol. Chem. (IF 4.0) Pub Date : 2024-09-10 Yubing Li,Yipeng Zhao,Yaojun He,Fang Liu,Lu Xia,Kai Liu,Mingjie Zhang,Keyu Chen
ASAP1 and its paralog ASAP2 belong to a PI4,5P2-dependent Arf GTPase-activating protein (Arf-GAP) family capable of modulating membrane and cytoskeletal dynamics. ASAPs regulate cell adhesive structures such as invadosomes and focal adhesions during cell attachment and migration. Malfunctioning of ASAP1 has been implicated in the malignant phenotypes of various cancers. Here, we discovered that the
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Modeling protease-sensitive human pancreatic lipase mutations in the mouse ortholog. J. Biol. Chem. (IF 4.0) Pub Date : 2024-09-10 Gyula Hoffka,Samara Mhana,Marcell Vas,Vanda Toldi,János András Mótyán,József Tőzsér,András Szabó
Pancreatic lipase (PNLIP) is the major lipolytic enzyme secreted by the pancreas. A recent study identified human PNLIP variants P245A, I265R, F300L, S304F, and F314L in European chronic pancreatitis cohorts. Functional analyses indicated that the variants were normally secreted but exhibited reduced stability when exposed to pancreatic proteases. Proteolysis of the PNLIP variants yielded an intact
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Role of Ammonia Lyases in the Synthesis of the Dithiomethylamine Ligand During [FeFe]-hydrogenase Maturation. J. Biol. Chem. (IF 4.0) Pub Date : 2024-09-09 Adrien Pagnier,Batuhan Balci,Eric M Shepard,Hao Yang,Alex Drena,Gemma L Holliday,Brian M Hoffman,William E Broderick,Joan B Broderick
The generation of an active [FeFe]-hydrogenase requires the synthesis of a complex metal center, the H-cluster, by three dedicated maturases: the radical S-adenosyl-l-methionine (SAM) enzymes HydE and HydG, and the GTPase HydF. A key step of [FeFe]-hydrogenase maturation is the synthesis of the dithiomethylamine (DTMA) bridging ligand, a process recently shown to involve the aminomethyl-lipoyl-H-protein
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Murine Nuclear Tyrosyl-tRNA Synthetase Deficiency Leads to Fat Storage Deficiency and Hearing Loss. J. Biol. Chem. (IF 4.0) Pub Date : 2024-09-09 Julia A Jones,Jiadong Zhou,Jianjie Dong,Salvador Huitron-Resendiz,Ely Boussaty,Eduardo Chavez,Na Wei,Calin Dan Dumitru,Yosuke Morodomi,Taisuke Kanaji,Allen F Ryan,Rick Friedman,Tong Zhou,Sachiko Kanaji,Matthew Wortham,Simon Schenk,Amanda J Roberts,Xiang-Lei Yang
Aminoacyl-tRNA synthetases (aaRS) are fundamental to the translation machinery with emerging roles in transcriptional regulation. Previous cellular studies have demonstrated tyrosyl-tRNA synthetase (YARS1 or TyrRS) as a stress response protein through its cytosol-nucleus translocation to maintain cellular homeostasis. Here, we established a mouse model with a disrupted TyrRS nuclear localization signal
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Polymyxin B1 in the E. coli inner membrane: a complex story of protein and lipopolysaccharide mediated insertion. J. Biol. Chem. (IF 4.0) Pub Date : 2024-09-09 Dhanushka Weerakoon,Jan K Marzinek,Conrado Pedebos,Peter J Bond,Syma Khalid
The rise in multi-drug resistant Gram-negative bacterial infections has led to an increased need for 'last-resort' antibiotics such as polymyxins. However, the emergence of polymyxin-resistant strains threatens to bring about a post-antibiotic era. Thus, there is a need to develop new polymyxin-based antibiotics, but a lack of knowledge of the mechanism of action of polymyxins hinders such efforts
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Probing the nucleobase selectivity of RNA polymerases with dual-coding substrates. J. Biol. Chem. (IF 4.0) Pub Date : 2024-09-09 Janne J Mäkinen,Petja Rosenqvist,Pasi Virta,Mikko Metsä-Ketelä,Georgiy A Belogurov
Formycin A (FOR) and Pyrazofurin A (PYR) are nucleoside analogues with antiviral and antitumor properties. They are known to interfere with nucleic acid metabolism, but their direct effect on transcription is less understood. We explored how RNA polymerases (RNAPs) from bacteria, mitochondria, and viruses utilize FOR, PYR, and oxidized purine nucleotides. All tested polymerases incorporated FOR in
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Cortisol affects macrophage polarization by inducing miR-143/145 cluster to reprogram glucose metabolism and by promoting TCA cycle anaplerosis. J. Biol. Chem. (IF 4.0) Pub Date : 2024-09-09 Amod Sharma,Kunwar Somesh Vikramdeo,Sarabjeet Kour Sudan,Shashi Anand,Sachin Kumar Deshmukh,Ajay Pratap Singh,Seema Singh
Chronic stress can have adverse consequences on human health by disrupting the hormonal balance in our body. Earlier, we observed elevated levels of cortisol, a primary stress hormone, and some exosomal microRNAs in the serum of breast cancer patients. Here, we investigated the role of cortisol in microRNA induction and its functional consequences. We found that cortisol induced the expression of miR-143/145
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The pro-inflammatory cytokines IL-1β and IL-6 promote upregulation of the ST6GAL1 sialyltransferase in pancreatic cancer cells. J. Biol. Chem. (IF 4.0) Pub Date : 2024-09-09 Austin D Silva,Jihye Hwang,Michael P Marciel,Susan L Bellis
The ST6GAL1 sialyltransferase is overexpressed in multiple cancers including pancreatic ductal adenocarcinoma (PDAC). ST6GAL1 adds an α2-6-linked sialic acid to N-glycosylated membrane receptors, which consequently modulates receptor structure and function. While many studies have investigated the effects of ST6GAL1 on cell phenotype, there is a dearth of knowledge regarding mechanisms that regulate
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Impaired endocytosis and accumulation in early endosomal compartments defines herpes simplex virus-mediated disruption of the non-classical MHC class I-related molecule MR1. J. Biol. Chem. (IF 4.0) Pub Date : 2024-09-09 Carolyn Samer,Hamish E G McWilliam,Brian P McSharry,James G Burchfield,Richard J Stanton,Jamie Rossjohn,Jose A Villadangos,Allison Abendroth,Barry Slobedman
Presentation of metabolites by the Major Histocompatibility Complex Class-I-related protein 1 (MR1) molecule to Mucosal-Associated Invariant T (MAIT) cells is impaired during herpes simplex type 1 (HSV-1) and type 2 (HSV-2) infections. This is surprising given these viruses do not directly synthesise MR1 ligands. We have previously identified several HSV proteins responsible for rapidly downregulating
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A venom peptide-induced NaV channel modulation mechanism involving the interplay between fixed channel charges and ionic gradients. J. Biol. Chem. (IF 4.0) Pub Date : 2024-09-09 Ashvriya Thapa,Jia Hao Beh,Samuel D Robinson,Jennifer R Deuis,Hue Tran,Irina Vetter,Angelo Keramidas
Venoms are used by arthropods either to immobilise prey or as defence against predators. Our study focuses on the venom peptide, Ta3a, from the African ant species, Tetramorium africanum and its effects on voltage-gated sodium (NaV) channels, which are ion channels responsible for the generation of electrical signals in electrically excitable cells, such as neurons. Using the NaV1.7 isoform as our
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A novel phospholipase A2 is a core component of the typhoid toxin genetic islet. J. Biol. Chem. (IF 4.0) Pub Date : 2024-09-09 Sarah C Gartly,Luke A F Barretto,Anne-Charlotte M T Côté,Zach A Kosowan,Casey C Fowler
S. Typhi, the cause of typhoid fever, is a bacterial pathogen of substantial global importance. Typhoid toxin is a secreted AB-type toxin that is a key S. Typhi virulence factor encoded within a 5-gene genetic islet. Four genes in this islet have well-defined roles in typhoid toxin biology, however the function of the fifth gene is unknown. Here, we investigate the function of this gene, which we name
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A Cub and Sushi domain containing protein with esterase like activity confers insecticide resistance in Indian malaria vector- Anopheles stephensi. J. Biol. Chem. (IF 4.0) Pub Date : 2024-09-09 Jatin Kumar,Ankit Kumar,Yash Gupta,Kapil Vashisht,Shivam Kumar,Arvind Sharma,Raj Kumar,Ashoke Sharon,Praveen K Tripathi,Ram Das,Om Prakash Singh,Shailja Singh,Soumyananda Chakraborti,Sujatha Sunil,Kailash C Pandey
Chemical insecticides (organophosphates and pyrethroids) in the form of IRS (Indoor Residual Sprays) and LLINs (Long Lasting insecticidal nets) are the cornerstone for vector control, globally. However, their incessant use has resulted in widespread development of resistance in mosquito vectors, warranting continuous monitoring and investigation of the underlying mechanisms of resistance. Here, we
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Deubiquitinating enzyme USP39 promotes the growth and metastasis of gastric cancer cells by modulating the degradation of RNA-binding protein RBM39. J. Biol. Chem. (IF 4.0) Pub Date : 2024-09-09 Chengpiao Lu,Yunxin Cai,Shenglong Wu,Yuhong Wang,Jia-Bin Li,Guoqiang Xu,Jingjing Ma
It has been revealed recently that the RNA-binding motif protein RBM39 is highly expressed in several cancers, which results in poor patient survival. However, how RBM39 is regulated in gastric cancer cells is unknown. Here, affinity purification-mass spectrometry and a biochemical screening are employed to identify the RBM39-interacting proteins and the deubiquitinating enzymes (DUBs) that regulate
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Profiling metabolome of mouse embryonic cerebrospinal fluid following maternal immune activation. J. Biol. Chem. (IF 4.0) Pub Date : 2024-09-07 Boryana Petrova,Tiara E Lacey,Andrew J Culhane,Jin Cui,Jeannette R Brook,Alexander Raskind,Aditya Misra,Maria K Lehtinen,Naama Kanarek
The embryonic cerebrospinal fluid (eCSF) plays an essential role in the development of the central nervous system (CNS), influencing processes from neurogenesis to lifelong cognitive functions. An important process affecting eCSF composition is inflammation. Inflammation during development can be studied using the maternal immune activation (MIA) mouse model, which displays altered cytokine eCSF composition
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A "terminal" case of glycan catabolism: structural and enzymatic characterization of the sialidases of Clostridium perfringens. J. Biol. Chem. (IF 4.0) Pub Date : 2024-09-07 Brendon J Medley,Kristin E Low,Jackline D W Irungu,Linus Kipchumba,Parandis Daneshgar,Lin Liu,Jolene M Garber,Leeann Klassen,G Douglas Inglis,Geert-Jan Boons,Wesley F Zandberg,D Wade Abbott,Alisdair B Boraston
Sialic acids are commonly found on the terminal ends of biologically important carbohydrates, including intestinal mucin O-linked glycans. Pathogens such as Clostridium perfringens, the causative agent of necrotic enteritis (NE) in poultry and humans, have the ability to degrade host mucins and colonize the mucus layer, which involves removal of the terminal sialic acid by carbohydrate-active enzymes
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The Rapid-reaction Kinetics of an Electron-Bifurcating Flavoprotein, the crotonyl-CoA-dependent NADH:ferredoxin oxidoreductase EtfAB:bcd. J. Biol. Chem. (IF 4.0) Pub Date : 2024-09-03 Derek Nguyen,Wayne Vigil,Dimitri Niks,Russ Hille
We have investigated the kinetic behavior of the electron-bifurcating crotonyl-CoA-dependent NADH: ferredoxin oxidoreductase EtfAB:bcd from Megasphaera elsdenii. The overall behavior of the complex in both the reductive and oxidative half-reactions is consistent with that previously determined for the individual EtfAB and bcd components. This includes an uncrossing of the half-potentials of the bifurcating
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Translation arrest cancellation of VemP, a secretion monitor in Vibrio, is regulated by multiple cis- and trans-factors, including SecY. J. Biol. Chem. (IF 4.0) Pub Date : 2024-09-02 Yuki Ikeda,Ryoji Miyazaki,Tomoya Tsukazaki,Yoshinori Akiyama,Hiroyuki Mori
VemP is a secretory protein in the Vibrio species that monitors cellular protein-transport activity through its translation arrest, allowing expression of the downstream secD2-secF2 genes in the same operon, which encode components of the protein translocation machinery. When cellular protein-transport function is fully active, secD2/F2 expression remains repressed as VemP translation arrest is canceled
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Crossing the membrane - what does it take to flip a phospholipid? Structural and biochemical advances on P4-ATPase flippases. J. Biol. Chem. (IF 4.0) Pub Date : 2024-09-02 Kadambari Vijay Sai,Jyh-Yeuan Lee
Membrane asymmetry is critical for maintenance of several different processes such as cell signalling, apoptosis, and vesicular transport in various eukaryotic systems. Flippases of the P4-ATPase family are associated with flipping phospholipids from the luminal or exoplasmic leaflet to the cytosolic leaflet. P4-ATPases belong to the P-type ATPase family, which are activated by phosphorylation and
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TRAF3 regulates STAT6 activation and T helper cell differentiation by modulating the phosphatase PTP1B. J. Biol. Chem. (IF 4.0) Pub Date : 2024-09-02 Tina Arkee,Emma L Hornick,Gail A Bishop
The adaptor protein TNFR associated factor 3 (TRAF3) is a multifaceted regulator of lymphocyte biology that plays key roles in modulation of the molecular signals required for T cell activation and function. TRAF3 regulates signals mediated by the T cell receptor (TCR), costimulatory molecules, and cytokine receptors, which each drive activation of the serine/threonine kinase Akt. The impact of TRAF3
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Inhibition of Transient Receptor Potential Vanilloid 3 Channels by Antimalarial Hydroxychloroquine (HCQ) Alleviates TRPV3-dependent Dermatitis. J. Biol. Chem. (IF 4.0) Pub Date : 2024-09-02 Beilei Zhang,Bo Xie,Wen Xu,Dongfan Wei,Li Zhang,Jiayi Sun,Yetan Shi,Jiangfeng Feng,Fan Yang,Heng Zhang,Xiuzu Song
Transient receptor potential vanilloid 3 channel (TRPV3) is closely associated with skin inflammation, but there is a lack of effective and specific inhibitors for clinical use. In this study, we identified antimalarial HCQ as a selective TRPV3 inhibitor following the prediction by network pharmacology data analysis. In whole-cell patch-clamp recordings, HCQ inhibited the current of the TRPV3 channel
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alpha-synuclein, autophagy-lysosomal pathway, and Lewy bodies: mutations, propagation, aggregation, and the formation of inclusions. J. Biol. Chem. (IF 4.0) Pub Date : 2024-09-02 Armin Bayati,Peter S McPherson
Research into the pathophysiology of Parkinson's disease (PD) is a fast-paced pursuit, with new findings about PD and other synucleinopathies being made each year. The involvement of various lysosomal proteins, such as TFEB, TMEM175, GBA, and LAMP1/2, marks the rising awareness about the importance of lysosomes in PD and other neurodegenerative disorders. This, along with recent developments regarding
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Identification and characterization of transition metal-binding proteins and metabolites in the phloem sap of Brassica napus. J. Biol. Chem. (IF 4.0) Pub Date : 2024-08-31 Hendrik Küpper,Arun Gokul,Dario Alavez,Singha R Dhungana,Syed Nadeem Hussain Bokhari,Marshall Keyster,David G Mendoza-Cozatl
Transition metal (TM) distribution through the phloem is an essential part of plant metabolism and is required for systemic signaling and balancing source-to-sink relationships. Due to their reactivity, TMs are expected to occur in complexes within the phloem sap; however, metal speciation in the phloem sap remains largely unexplored. Here, we isolated phloem sap from Brassica napus and analyzed it
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Mycobacterium smegmatis putative Holliday junction resolvases RuvC and RuvX play complementary roles in the processing of branched DNA structures. J. Biol. Chem. (IF 4.0) Pub Date : 2024-08-31 Ankit Agarwal,Kalappa Muniyappa
In eubacteria, Holliday junction (HJ) resolvases (HJRs) are crucial for faithful segregation of newly replicated chromosomes, homologous recombination and repair of stalled/collapsed DNA replication forks. However, compared with the Escherichia coli HJRs, little is known about their orthologs in mycobacterial species. A genome-wide analysis of Mycobacterium smegmatis identified two genes encoding putative
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Structural analysis of noncanonical translation initiation complexes. J. Biol. Chem. (IF 4.0) Pub Date : 2024-08-31 Jacob M Mattingly,Ha An Nguyen,Bappaditya Roy,Kurt Fredrick,Christine M Dunham
Translation initiation is a highly regulated, multi-step process which is critical for efficient and accurate protein synthesis. In bacteria, initiation begins when mRNA, initiation factors, and a dedicated initiator fMet-tRNAfMet bind the small (30S) ribosomal subunit. Specific binding of fMet-tRNAfMet in the peptidyl (P) site is mediated by the inspection of the fMet moiety by initiation factor IF2
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KAT Tales: Functions of Gcn5 and PCAF lysine acetyltransferases in SAGA and ATAC. J. Biol. Chem. (IF 4.0) Pub Date : 2024-08-31 Sharon Y R Dent
The Allis group identified Gcn5 as the first transcription-related lysine acetyltransferase in 1996, providing a molecular 'missing link' between chromatin organization and gene regulation. This review will focus on functions subsequently identified for Gcn5 and the closely related PCAF protein, in the context of two major complexes, SAGA and ATAC, and how the study of these enzymes informs long standing
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Virus-like particles as robust tools for functional assessment: Deciphering the pathogenicity of ABCA4 genetic variants of uncertain significance. J. Biol. Chem. (IF 4.0) Pub Date : 2024-08-31 Senem Cevik,Subhasis B Biswas,Arit Ghosh,Esther E Biswas-Fiss
The retina-specific ABCA transporter, ABCA4, is essential for vision, and its genetic variants are associated with a wide range of inherited retinal degenerative diseases (IRDs) leading to blindness. Of the 1,630 identified missense variants in ABCA4, ∼50% are of unknown pathogenicity (variants of unknown significance, VUS). This genetic uncertainty presents three main challenges: (i) inability to
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Characterization of lignin degrading enzyme PmdC, which catalyzes a key step in the synthesis of polymer precursor 2-pyrone-4,6-dicarboxylic acid (PDC). J. Biol. Chem. (IF 4.0) Pub Date : 2024-08-31 Andria V Rodrigues,Nigel W Moriarty,Ramu Kakumanu,Andy DeGiovanni,Jose Henrique Pereira,Jennifer W Gin,Yan Chen,Edward E K Baidoo,Christopher J Petzold,Paul D Adams
Pyrone-2,4-dicarboxylic acid (PDC) is a valuable polymer precursor that can be derived from the microbial degradation of lignin. The key enzyme in the microbial production of PDC is CHMS dehydrogenase, which acts on the substrate 4-carboxy-2-hydroxymuconate-6-semialdehyde (CHMS). We present the crystal structure of CHMS dehydrogenase (PmdC from Comamonas testosteroni) bound to the cofactor NADP, shedding
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Delineation of the substrate recognition domain of MARCHF6 E3 ubiquitin ligase in the Ac/N-degron pathway and its regulatory role in ferroptosis J. Biol. Chem. (IF 4.0) Pub Date : 2024-08-30 Jihye Yang, Sang-Yoon Kim, Cheol-Sang Hwang
Nα-terminal acetylation in eukaryotic proteins creates specific degradation signals (Ac/N-degrons) targeted for ubiquitin-mediated proteolysis the Ac/N-degron pathway. Despite the identification of key components of the Ac/N-degron pathway over the past 15 years, the precise recognition domain (Ac/N domain) remains unclear. Here, we defined the Ac/N domain of the endoplasmic reticulum MARCHF6 E3 ubiquitin
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Tau-mediated coupling between Pol III synthesis and DnaB helicase unwinding helps maintain genomic stability J. Biol. Chem. (IF 4.0) Pub Date : 2024-08-29 Malisha U. Welikala, Lauren J. Butterworth, Megan S. Behrmann, Michael A. Trakselis
The τ-subunit of the clamp loader complex physically interacts with both the DnaB helicase and the polymerase III (Pol III) core α-subunit through domains IV and V, respectively. This interaction is proposed to help maintain rapid and efficient DNA synthesis rates with high genomic fidelity and plasticity, facilitating enzymatic coupling within the replisome. To test this hypothesis, CRISPR-Cas9 editing
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Hinokiflavone resists HFD-induced obesity by promoting apoptosis in an IGF2BP2-mediated Bim m6A modification dependent manner J. Biol. Chem. (IF 4.0) Pub Date : 2024-08-29 Mingyu Wang, Mingkun Chao, Haozhe Han, Tiantian Zhao, Wenyong Yan, Gongshe Yang, Weijun Pang, Rui Cai
Obesity has emerged as a major health risk on a global scale. Hinokiflavone (HF), a natural small molecule, extracted from plants like cypress, exhibits diverse chemical structures and low synthesis costs. Using high-fat diet-induced obese mice models, we found that HF suppresses obesity by inducing apoptosis in adipose tissue. Adipocyte apoptosis helps maintain tissue health by removing aging, damaged
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T7 RNA polymerase catalyzed transcription of the epimerizable DNA lesion, Fapy•dG and 8-oxo-2′-deoxyguanosine J. Biol. Chem. (IF 4.0) Pub Date : 2024-08-29 Shijun Gao, Peini Hou, Dong Wang, Marc M. Greenberg
Fapy•dG (6-(2-deoxy-α,β-D-erythro-pentofuranosyl)-2,6-diamino-4-hydroxy-5-formamidopyrimidine) and 8-OxodGuo (8-oxo-7,8-dihydro-2′-deoxyguanosine) are major products of 2′-deoxyguanosine oxidation. Fapy•dG is unusual in that it exists as a dynamic mixture of anomers. Much less is known about the effects of Fapy•dG than 8-OxodGuo on transcriptional bypass. The data presented here indicate that T7 RNA
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Fusion of FokI and catalytically inactive prokaryotic Argonautes enables site-specific programmable DNA cleavage J. Biol. Chem. (IF 4.0) Pub Date : 2024-08-28 Qiaochu Wang, Gundra Sivakrishna Rao, Tin Marsic, Rashid Aman, Magdy Mahfouz
Site-specific nucleases are crucial for genome engineering applications in medicine and agriculture. The ideal site-specific nucleases are easily reprogrammable, highly specific in target site recognition, and robust in nuclease activities. Prokaryotic Argonaute (pAgo) proteins have received much attention as biotechnological tools due to their ability to recognize specific target sequences without
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Alzheimer’s disease seeded tau forms paired helical filaments yet lacks seeding potential J. Biol. Chem. (IF 4.0) Pub Date : 2024-08-28 Pu Duan, Aurelio J. Dregni, Hong Xu, Lakshmi Changolkar, Virginia M-Y. Lee, Edward B. Lee, Mei Hong
Alzheimer’s disease (AD) and many other neurodegenerative diseases are characterized by pathological aggregation of the protein tau. These tau aggregates spread in a stereotypical spatiotemporal pattern in the brain of each disease, suggesting that the misfolded tau can recruit soluble monomers to adopt the same pathological structure. To investigate whether recruited tau indeed adopts the same structure
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Overexpression of RBM4 promotes acute myeloid leukemia cell differentiation by regulating alternative splicing of TFEB J. Biol. Chem. (IF 4.0) Pub Date : 2024-08-28 Yu Duan, Sijin Liu, Jinjuan Wang, Kai Yang, Jing Xu, Qirong Wang, Jianbing Liu, Jianqing Hao, Xiaohua Cui, Yanhong Tan, Hongwei Wang, Li Li
Alternative splicing is an efficient and ubiquitous transcriptional regulatory mechanism that expands the coding capacity of the genome and is associated with the occurrence and progression of cancer. The differentiation-promoting regimen is a potential therapeutic approach in cancer treatment. In this study, we screened NPMc-positive and NPMc-negative acute myeloid leukemia (AML) samples from the
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Multifaceted regulation of sirtuin 2 (Sirt2) deacetylase activity J. Biol. Chem. (IF 4.0) Pub Date : 2024-08-28 Maheeshi Yapa Abeywardana, Samuel D. Whedon, Kwangwoon Lee, Eunju Nam, Rafael Dovarganes, Sarah Dubois-Coyne, Ishraq A. Haque, Zhipeng A. Wang, Philip A. Cole
Sirtuin 2 (Sirt2) is a member of the sirtuin family of NAD-dependent lysine deacylases and plays important roles in regulation of the cell cycle and gene expression. As a nucleocytoplasmic deacetylase, Sirt2 has been shown to target both histone and nonhistone acetylated protein substrates. The central catalytic domain of Sirt2 is flanked by flexible N and C termini, which vary in length and composition
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Autoinhibition of ubiquitin-specific protease 8: Insights into domain interactions and mechanisms of regulation J. Biol. Chem. (IF 4.0) Pub Date : 2024-08-28 Cody Caba, Megan Black, Yujue Liu, Ashley A. DaDalt, Josh Mallare, Lixin Fan, Rachel J. Harding, Yunxin Wang, Panayiotis O. Vacratsis, Rui Huang, Zhihao Zhuang, Yufeng Tong
Ubiquitin-specific proteases (USPs) are a family of multi-domain deubiquitinases (DUBs) with variable architectures, some containing regulatory auxiliary domains. Among the USP family, all occurrences of intramolecular regulation presently known are autoactivating. USP8 remains the sole exception as its putative WW-like domain, conserved only in vertebrate orthologs, is autoinhibitory. Here, we present
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Novel mechanism of cyclic nucleotide crosstalk mediated by PKG-dependent proteasomal degradation of the Hsp90 client protein phosphodiesterase 3A J. Biol. Chem. (IF 4.0) Pub Date : 2024-08-28 Evgeny A. Zemskov, Marina A. Zemskova, Xiaomin Wu, Santiago Moreno Caceres, David Caraballo Delgado, Manivannan Yegambaram, Qing Lu, Panfeng Fu, Ting Wang, Stephen M. Black
Endothelial cAMP-specific phosphodiesterase PDE3A is one of the major negative regulators of the endothelial barrier function in acute lung injury models. However, the mechanisms underlying its regulation still need to be fully resolved. We show here that the PDE3A is a newly described client of the molecular chaperone heat shock protein 90 (hsp90). In endothelial cells (ECs), hsp90 inhibition by geldanamycin
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Interaction between the TBC1D24 TLDc domain and the KIBRA C2 domain is disrupted by two epilepsy-associated TBC1D24 missense variants J. Biol. Chem. (IF 4.0) Pub Date : 2024-08-28 Risa Tona, Sayaka Inagaki, Yasuko Ishibashi, Rabia Faridi, Rizwan Yousaf, Isabelle Roux, Elizabeth Wilson, Cristina Fenollar-Ferrer, Wade W. Chien, Inna A. Belyantseva, Thomas B. Friedman
Mutations of human are associated with deafness, epilepsy, or DOORS syndrome (deafness, onychodystrophy, osteodystrophy, cognitive disability, and seizures). The causal relationships between variants and the different clinical phenotypes are not understood. Our hypothesis is that phenotypic heterogeneity of missense mutations of results, in part, from perturbed binding of different protein partners
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Nonstructural protein 4 of human norovirus self-assembles into various membrane-bridging multimers J. Biol. Chem. (IF 4.0) Pub Date : 2024-08-28 Adrien Royet, Rémi Ruedas, Laetitia Gargowitsch, Virginie Gervais, Johann Habersetzer, Laura Pieri, Malika Ouldali, Maïté Paternostre, Ilse Hofmann, Thibault Tubiana, Sonia Fieulaine, Stéphane Bressanelli
Single-stranded, positive-sense RNA ((+)RNA) viruses replicate their genomes in virus-induced intracellular membrane compartments. (+)RNA viruses dedicate a significant part of their small genomes (a few thousands to a few tens of thousands of bases) to the generation of these compartments by encoding membrane-interacting proteins and/or protein domains. Noroviruses are a very diverse genus of (+)RNA
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Defective post-transcriptional modification of tRNA disrupts mitochondrial homeostasis in Leber’s hereditary optic neuropathy J. Biol. Chem. (IF 4.0) Pub Date : 2024-08-28 Juanjuan Zhang, Wenxu Li, Zhen liu, Yingqi Chen, Xiaoyang Wei, Lu Peng, Man Xu, Yanchun Ji
Leber's Hereditary Optic Neuropathy (LHON) is a rare, maternally inherited eye disease, predominantly due to the degeneration of retinal ganglion cells (RGCs). It is associated with a mitochondrial DNA (mtDNA) point mutation. Our previous study identified that the m.15927G > A homoplasmic mutation damaged the highly conserved base pairing (28C-42G) in anticodon stem of tRNA, caused deficient tA modification
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Rhodoquinone-dependent electron transport chain is essential for Caenorhabditis elegans survival in hydrogen sulfide environments J. Biol. Chem. (IF 4.0) Pub Date : 2024-08-22 Laura Romanelli-Cedrez, Franco vairoletti, Gustavo Salinas
Hydrogen sulfide (HS) has traditionally been considered an environmental toxin for animal lineages; yet, it plays a signaling role in various processes at low concentrations. Mechanisms controlling HS in animals, especially in sulfide-rich environments, are not fully understood. The main detoxification pathway involves the conversion of HS into less harmful forms, through a mitochondrial oxidation
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A heterocyclic compound inhibits viral release by inducing cell surface BST2/Tetherin/CD317/HM1.24 J. Biol. Chem. (IF 4.0) Pub Date : 2024-08-22 Perpetual Nyame, Akihiro Togami, Tomofumi Yoshida, Takuya Masunaga, M.S.T. Monira Begum, Hiromi Terasawa, Nami Monde, Yurika Tahara, Reiko Tanaka, Yuetsu Tanaka, Joyce Appiah-Kubi, Wright Ofotsu Amesimeku, Md Jakir Hossain, Masami Otsuka, Kazuhisa Yoshimura, Terumasa Ikeda, Tomohiro Sawa, Yorifumi Satou, Mikako Fujita, Yosuke Maeda, Hiroshi Tateishi, Kazuaki Monde
The introduction of combined antiretroviral therapy (cART) has greatly improved the quality of life of human immunodeficiency virus type 1 (HIV-1)-infected individuals. Nonetheless, the ever-present desire to seek out a full remedy for HIV-1 infections makes the discovery of novel antiviral medication compelling. Owing to this, a new late-stage inhibitor, Lenacapavir/Sunlenca, an HIV multi-phase suppressor
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Docking interactions determine substrate specificity of members of a widespread family of protein phosphatases J. Biol. Chem. (IF 4.0) Pub Date : 2024-08-22 Suhaily Caban-Penix, Kristin Ho, Zhewen Yang, Rishika Baral, Niels Bradshaw
How protein phosphatases achieve specificity for their substrates is a major outstanding question. PPM family serine/threonine phosphatases are widespread in bacteria and eukaryotes, where they dephosphorylate target proteins with a high degree of specificity. In bacteria, PPM phosphatases control diverse transcriptional responses by dephosphorylating anti-anti-sigma factors of the STAS domain family
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CupAR negatively controls the key protein CupA in the carbon acquisition complex NDH–1MS in Synechocystis sp. PCC 6803 J. Biol. Chem. (IF 4.0) Pub Date : 2024-08-22 Jiexi Liu, Fangfang Zheng, Min Xu, Teruo Ogawa, Hualing Mi
The low CO-inducible NDH complex (NDH–1MS) plays a crucial role in the cyanobacterial CO-concentrating mechanism. However, the components in this complex and the regulation mechanism are still not completely understood. Using a mutant only with NDH–1MS as active Ci sequestration system, we identified a functional gene named as (CupA Regulator). The deletion mutant, , grew faster than the WT under high
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Direct detection of the chloride release and uptake reactions of Natronomonas pharaonis halorhodopsin J. Biol. Chem. (IF 4.0) Pub Date : 2024-08-22 Chihaya Hamada, Keisuke Murabe, Takashi Tsukamoto, Takashi Kikukawa
Membrane transport proteins undergo multistep conformational changes to fulfill the transport of substrates across biological membranes. Substrate release and uptake are the most important events of these multistep reactions that accompany significant conformational changes. Thus, their relevant structural intermediates should be identified to better understand the molecular mechanism. However, their
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Comprehensive analysis of consensus molecular subtypes for ovarian cancer from bulk to single-cell perspectives J. Biol. Chem. (IF 4.0) Pub Date : 2024-08-22 Ziyan Zhao, Linan Xing, Qian Cheng, Zhiyi Wu, Fei Xue, Yunyi Peng, Yuxi Zhang, Guixiang Lv, Yongjian Zhang, Chunlong Zhang
Molecular subtypes play a pivotal role in guiding preclinical and clinical risk assessment and treatment strategies in cancer. In this study, we extracted whole-tissue transcriptomic data from 1987 ovarian cancer patients spanning 26 independent Gene Expression Omnibus cohorts. A total of four consensus subtypes (C1–C4) were identified, notably, subtype C1 samples exhibited a poor prognosis and higher
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O-GlcNAcylation in tumorigenesis and its implications for cancer therapy J. Biol. Chem. (IF 4.0) Pub Date : 2024-08-22 Dize Zhang, Yihang Qi, Hiroyuki Inuzuka, Jing Liu, Wenyi Wei
O-linked N-acetylglucosaminylation (O-GlcNAcylation) is a dynamic and reversible posttranslational modification that targets serine and threonine residues in a variety of proteins. Uridine diphospho-N-acetylglucosamine, which is synthesized from glucose the hexosamine biosynthesis pathway, is the major donor of this modification. O-GlcNAc transferase is the sole enzyme that transfers GlcNAc onto protein