1,569,242 results match your criteria binding affinity

The lncRNA OGFRP1/miR-149-5p/IL-6 axis regulates prostate cancer chemoresistance.

Pathol Res Pract 2021 Jun 22;224:153535. Epub 2021 Jun 22.

Department of Laboratory Medicine, Shanghai University of Medicine & Health Sciences Affiliated Zhoupu Hospital, Shanghai 201318, China. Electronic address:

Background: The long non-coding RNA (lncRNA) OGFRP1 has been found to promote malignancy in prostate cancer (PC) and other cancer types. How this lncRNA functions in the regulation of PC chemoresistance, however, is poorly defined.

Methods: qRT-PCR was employed to measure OGFRP1, miR-149-5p, and IL-6 expression in PC tissues and cells. Read More

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Topical cationic hairy particles targeting cell free DNA in dermis enhance treatment of psoriasis.

Biomaterials 2021 Jul 15;276:121027. Epub 2021 Jul 15.

School of Materials Science and Engineering, Key Laboratory for Polymeric Composite and Functional Materials of Ministry of Education, GD Research Center for Functional Biomaterials Engineering and Technology, Sun Yat-sen University, 510275, Guangzhou, China. Electronic address:

Abnormal high level of cell free DNA (cfDNA) triggers chronic inflammation to exacerbate psoriasis symptoms. Scavenging cfDNA by topical cationic polymeric nanoparticles has been certified as an effective therapeutic strategy for treating psoriasis. However, cationic cfDNA scavengers have a great potential risk to organs after entering systemic circulation through skin barrier. Read More

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Reconsidering pathway choice: a sequential model of mammalian DNA double-strand break pathway decisions.

Tanya T Paull

Curr Opin Genet Dev 2021 Jul 19;71:55-62. Epub 2021 Jul 19.

The University of Texas at Austin, Department of Molecular Biosciences, Austin, TX, 78712, United States. Electronic address:

DNA double-strand breaks can be repaired through ligation-based pathways (non-homologous end-joining) or replication-based pathways (homologous recombination) in eukaryotic cells. The decisions that govern these outcomes are widely viewed as a competition between factors that recognize DNA ends and physically promote association of factors specific to each pathway, commonly known as 'pathway choice'. Here I review recent results in the literature and propose that this decision is better described as a sequential set of binding and end processing events, with non-homologous end joining as the first decision point. Read More

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Structural insights in galectin-1-glycan recognition: Relevance of the glycosidic linkage and the N-acetylation pattern of sugar moieties.

Bioorg Med Chem 2021 Jul 14;44:116309. Epub 2021 Jul 14.

Laboratorio de Bioquímica, Departamento de Biociencias, Facultad de Química, UdelaR, Gral. Flores, 2124, 11800 Montevideo, Uruguay. Electronic address:

Galectins, soluble lectins widely expressed intra- and extracellularly in different cell types, play major roles in deciphering the cellular glycocode. Galectin-1 (Gal-1), a prototype member of this family, presents a carbohydrate recognition domain (CRD) with specific affinity for β-galactosides such as N-acetyllactosamine (β-d-Galp-(1 → 4)-d-GlcpNAc), and mediate numerous physiological and pathological processes. In this work, Gal-1 binding affinity for β-(1 → 6) galactosides, including β-d-Galp-(1 → 6)-β-d-GlcpNAc-(1 → 4)-d-GlcpNAc was evaluated, and their performance was compared to that of β-(1 → 4) and β-(1 → 3) galactosides. Read More

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Proteome and transcriptome analysis revealed florfenicol via affected drug metabolism and lipid metabolism induce liver injury of broilers.

Poult Sci 2021 May 4;100(9):101228. Epub 2021 May 4.

College of Traditional Chinese Veterinary Medicine, Agriculture University of Hebei, Baoding, 071001, China; Hebei Veterinary Biotechnology Innovation Center, Baoding 071000, China.

In order to explore the mechanism of liver injury induced by florfenicol (FFC) in broilers. Sixty broilers were randomly divided into 2 groups: control group: normal drinking water and feed were given every d; FFC group: tap water containing FFC (0.15g/L) was given every d and feed was taken freely; each group was given 5 dd of continuous medication and feed was taken freely. Read More

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Monomeric C-reactive protein promotes platelets to release mitochondrial DNA in anti-neutrophil cytoplasmic antibody-associated vasculitis.

Mol Immunol 2021 Jul 19;137:228-237. Epub 2021 Jul 19.

Department of Nephrology, Tianjin Medical University General Hospital, Tianjin, 300052, China. Electronic address:

Although high level of circulating C-reactive protein (pCRP) is considered as a biomarker for disease activity, the significance of CRP in the pathogenesis of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) has not been clarified. We once reported in AAV, pentameric CRP (pCRP) could dissociate into monomeric CRP (mCRP) and activate platelets. Recent studies have demonstrated that the activated platelets can release mitochondrial DNA (mtDNA). Read More

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A new strategy for the development of efficient impedimetric tobramycin aptasensors with metallo-covalent organic frameworks (MCOFs).

Food Chem 2021 Jul 12;366:130575. Epub 2021 Jul 12.

College of Material and Chemical Engineering, Zhengzhou University of Light Industry, Zhengzhou 450001, PR China. Electronic address:

Two bimetallic CoNi-based metallo-covalent organic frameworks (MCOFs) were prepared and explored as the sensitive platforms of impedimetric aptasensors for efficient detection of tobramycin (TOB). The two CoNi-MCOFs were constructed using metallophthalocyanine tetra-amine (MPc-TA, M = Co or Ni) and 4,4'-(1,10-phen-anthroline-2,9-diyl) dibenzaldehyde (PTD) as building units and further coordinating to the secondary metal ions (Ni or Co) by phenanthroline. Interestingly, the immobilization ability of CoPc-TA-PTD(Ni) to TOB-targeted aptamer is higher than that of NiPc-TA-PTD(Co) due to its stronger binding interactions to aptamer. Read More

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Mig6 not only inhibits EGFR and HER2 but also targets HER3 and HER4 in a differential specificity: Implications for targeted esophageal cancer therapy.

Biochimie 2021 Jul 19. Epub 2021 Jul 19.

Department of Thoracic Surgery, Huiqiao Medical Center, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China. Electronic address:

The human EGF receptor family plays pivotal roles in physiology and cancer, which contains four closely-related members: HER1/EGFR, HER2, HER3 and HER4. Previously, it was found that the mitogen-inducible gene 6 (Mig6) protein is a negative regulator of EGFR and HER2 by using its S1 segment to bind at the kinase dimerization interface. However, it is still unclear whether the S1 segment can also effectively target HER3 and HER4? Here, we performed a systematic investigation to address this issue. Read More

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Fatty acids and evolving roles of their proteins in neurological, cardiovascular disorders and cancers.

Prog Lipid Res 2021 Jul 20;83:101116. Epub 2021 Jul 20.

Department of Nutrition, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Norway. Electronic address:

The dysregulation of fat metabolism is involved in various disorders, including neurodegenerative, cardiovascular, and cancers. The uptake of long-chain fatty acids (LCFAs) with 14 or more carbons plays a pivotal role in cellular metabolic homeostasis. Therefore, the uptake and metabolism of LCFAs must constantly be in tune with the cellular, metabolic, and structural requirements of cells. Read More

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Design and evaluation of GLP-1 receptor G-protein biased agonist with prolonged efficacy on diabetes.

Life Sci 2021 Jul 19:119844. Epub 2021 Jul 19.

Peking University Third Hospital, Beijing 100191, PR China. Electronic address:

Aim: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have emerged as potent drug development target for treating diabetes and obesity. Here, we designed and evaluated novel long-acting GLP-1R G protein biased agonist with potent clinical application.

Main Methods: GLP-1R G-protein biased sequences were screened via a high-throughput autocrine-based strategy and then fused to Exendin (9-39). Read More

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Efficient biosynthesis of D-allulose in Bacillus subtilis through D-psicose 3-epimerase translation modification.

Int J Biol Macromol 2021 Jul 20;187:1-8. Epub 2021 Jul 20.

College of Light Industry and Food Engineering, Guangxi University, 100 Daxue Road, Nanning 530004, Guangxi, China; Sugar Industry Collaborative Innovation Center, Guangxi University, 100 Daxue Road, Nanning 530004, Guangxi, China. Electronic address:

The combined catalysis of glucose isomerase (GI) and D-psicose 3-epimerase (DPEase) provided a convenient route for the direct synthesis of D-allulose from d-glucose, whose cost is lower than d-fructose. In the present research, the weak activity of DPEase was the key rate-limiting step and resulted in the accumulation of d-fructose in engineered Bacillus subtilis. Then, the 5'-untranslated region (5'-UTR) structure of the mRNA translational initiation region was optimized for the precise control of DPEase expression. Read More

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PDL1 triggered by binding eIF3I contributes to the amelioration of diabetes-associated wound healing defects by regulating IRS4.

J Invest Dermatol 2021 Jul 19. Epub 2021 Jul 19.

Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200437, China; Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai, 200443, China. Electronic address:

Persistent chronic inflammation and delayed epithelialization lead to stalled healing in diabetic ulcers (DUs). PDL1 shows anti-inflammatory and proliferative activities in healing defects, while its function in DU pathogenesis remains unknown. Lower levels of PDL1 were found in DU tissues, and exogenous PDL1 has therapeutic effects in healing process by accelerating re-epithelialization and attenuating prolonged inflammation, which contributed to the delayed wound closure. Read More

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Oncogenic Hedgehog-smoothened signaling depends on YAP1-TAZ/TEAD transcription to restrain differentiation in basal cell carcinoma.

J Invest Dermatol 2021 Jul 19. Epub 2021 Jul 19.

Laboratory of Cellular and Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. Electronic address:

Disruption of the transcriptional activity of the Hippo pathway members YAP1 and TAZ has become a major target for cancer treatment. However, detailed analysis of the effectivity and networks affected by YAP1/TAZ transcriptional targeting are limited. Here, we utilize TEADi, an inhibitor of the binding of YAP1 and TAZ with their main transcriptional target TEAD in a mouse model of basal cell carcinoma (BCC) to unveil the consequences of YAP1/TAZ transcriptional inhibition in cancer cells. Read More

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Inhibition of CtBP-regulated proinflammatory gene transcription attenuates psoriatic skin inflammation.

J Invest Dermatol 2021 Jul 19. Epub 2021 Jul 19.

Department of Dermatology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA. Electronic address:

Psoriasis is a chronic immune-mediated disease characterized by excessive proliferation of epidermal keratinocytes and increased immune cell infiltration to the skin. Although it is well known that psoriasis pathogenesis is driven by aberrant production of proinflammatory cytokines, the mechanisms underlying the imbalance between proinflammatory and anti-inflammatory cytokine expression are incompletely understood. Here we report that the transcriptional coregulators C-terminal-binding protein (CtBP) 1 and 2 can transactivate a common set of proinflammatory genes both in the skin of imiquimod-induced mouse psoriasis model and in human keratinocytes and macrophages stimulated by imiquimod. Read More

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Nuclear IL-33 plays an important role in IL-31-mediated downregulation of filaggrin, keratin 1, and keratin 10 by regulating STAT3 activation in human keratinocytes.

J Invest Dermatol 2021 Jul 19. Epub 2021 Jul 19.

Department of Dermatology, Ehime University Graduate School of Medicine, Ehime, Japan.

Interleukin (IL)-33, a chromatin-associated multifunctional cytokine, is implicated in the pathogenesis of atopic dermatitis (AD), an inflammatory skin disorder characterized by skin barrier dysfunction. IL-33 accumulates in the nuclei of epidermal keratinocytes in AD lesions. However, it is unclear whether nuclear IL-33 directly contributes to the pathogenesis of AD. Read More

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Nicotinamide phosphoribosyltransferase inhibitors selectively induce apoptosis of AML stem cells by disrupting lipid homeostasis.

Cell Stem Cell 2021 Jul 12. Epub 2021 Jul 12.

Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada; Department of Medicine, University of Toronto, ON, Canada; Division of Medical Oncology and Hematology, Department of Medicine, University Health Network, Toronto, ON, Canada. Electronic address:

Current treatments for acute myeloid leukemia (AML) are often ineffective in eliminating leukemic stem cells (LSCs), which perpetuate the disease. Here, we performed a metabolic drug screen to identify LSC-specific vulnerabilities and found that nicotinamide phosphoribosyltransferase (NAMPT) inhibitors selectively killed LSCs, while sparing normal hematopoietic stem and progenitor cells. Treatment with KPT-9274, a NAMPT inhibitor, suppressed the conversion of saturated fatty acids to monounsaturated fatty acids, a reaction catalyzed by the stearoyl-CoA desaturase (SCD) enzyme, resulting in apoptosis of AML cells. Read More

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DNA sequence-dependent positioning of the linker histone in a nucleosome: a single-pair FRET study.

Biophys J 2021 Jul 19. Epub 2021 Jul 19.

Molecular and Cellular Modelling Group, Heidelberg Institute for Theoretical Studies (HITS), 69118 Heidelberg, Germany; Faculty of Biosciences, Heidelberg University, 69120 Heidelberg, Germany; Center for Molecular Biology (ZMBH), DKFZ-ZMBH Alliance, Heidelberg University, 69120 Heidelberg, Germany; Interdisciplinary Center for Scientific Computing (IWR), 69120 Heidelberg, Germany. Electronic address:

Linker histones (LH) bind to nucleosomes with their globular domain (gH) positioned in either an on- or an off-dyad binding mode. Here, we study the effect of the linker DNA (L-DNA) sequence on the binding of a full-length LH, Xenopus laevis H1.0b, to a Widom 601 nucleosome core particle (NCP) flanked by two 40 bp long L-DNA arms, by single-pair FRET spectroscopy. Read More

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Cell-type-specific meQTLs extend melanoma GWAS annotation beyond eQTLs and inform melanocyte gene-regulatory mechanisms.

Am J Hum Genet 2021 Jul 15. Epub 2021 Jul 15.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA. Electronic address:

Although expression quantitative trait loci (eQTLs) have been powerful in identifying susceptibility genes from genome-wide association study (GWAS) findings, most trait-associated loci are not explained by eQTLs alone. Alternative QTLs, including DNA methylation QTLs (meQTLs), are emerging, but cell-type-specific meQTLs using cells of disease origin have been lacking. Here, we established an meQTL dataset by using primary melanocytes from 106 individuals and identified 1,497,502 significant cis-meQTLs. Read More

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Controlling Coagulation in Blood with Red Light.

Angew Chem Int Ed Engl 2021 Jul 22. Epub 2021 Jul 22.

University of Frankfurt, Cluster of Excellence Macromolecular Complexes, Max-von-Laue-Str. 9, 60438, Frankfurt, GERMANY.

Precise control of blood clotting and rapid reversal of anticoagulation are essential in many clinical situations. We were successful in modifying a thrombin-binding aptamer with a red-light photocleavable linker derived from Cy7 by Cu-catalysed Click chemistry. We were able to show that we can successfully deactivate the modified aptamer with red light (660 nm) even in human blood - restoring the blood's natural coagulation capability. Read More

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Associations of genetically predicted circulating insulin-like growth factor-1 and insulin-like growth factor binding protein-3 with bladder cancer risk.

Mol Carcinog 2021 Jul 22. Epub 2021 Jul 22.

Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.

Insulin-like growth factors (IGF) play important roles in carcinogenesis. The associations of circulating IGF-1 and insulin-like growth factor-binding protein-3 (IGFBP-3) with the risks of bladder cancer remain unclear. In this large case control study of 2011 bladder cancer cases and 2369 heathy controls, we assessed the associations of circulating IGF-1 and IGFBP-3 with bladder cancer risks using a Mendelian randomization approach, which uses genetic variants as instruments to study causal relationship between risk factors and diseases. Read More

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Predicting mutant outcome by combining deep mutational scanning and machine learning.

Proteins 2021 Jul 22. Epub 2021 Jul 22.

Department of Computer Science, Ben-Gurion University of the Negev, Be'er Sheva, Israel.

Motivation: Deep mutational scanning provides unprecedented wealth of quantitative data regarding the functional outcome of mutations in proteins. A single experiment may measure properties (e.g. Read More

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Functional analysis of the odorant receptor coreceptor in odor detection in Grapholita molesta (lepidoptera: Tortricidae).

Arch Insect Biochem Physiol 2021 Jul 22:e21837. Epub 2021 Jul 22.

Key Laboratory of Plant Protection Resources & Pest Management of the Ministry of Education, College of Plant Protection, Northwest A&F University, Yangling, Shaanxi, China.

The olfactory system must detect and discriminate various semiochemicals in the environment. In response to such diversity, insects have evolved a family of odorant-gated ion channels composed of a common receptor (coreceptor, Orco) and a ligand-binding tuning odorant receptor (OR) that confers odour specificity. This study aims to examine the expression pattern of Orco gene of Grapholita molesta (GmolOrco) and to elucidate the role of GmolOrco in detecting G. Read More

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Affinity monolith chromatography: a review of general principles and recent developments.

Electrophoresis 2021 Jul 22. Epub 2021 Jul 22.

Department of Chemistry, University of Nebraska-Lincoln, Lincoln, NE, 68588, USA.

Affinity monolith chromatography (AMC) is a liquid chromatographic technique that utilizes a monolithic support with a biological ligand or related binding agent to isolate, enrich, or detect a target analyte in a complex matrix. The target-specific interaction exhibited by the binding agents makes AMC attractive for the separation or detection of a wide range of compounds. This article will review the basic principles of AMC and recent developments in this field. Read More

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Spectral Properties of Chlorophyll f in the B800 Cavity of Light-harvesting Complex 2 from the Purple Photosynthetic Bacterium Rhodoblastus acidophilus.

Photochem Photobiol 2021 Jul 22. Epub 2021 Jul 22.

Graduate School of Agricultural Science, Kobe University, Kobe, 657-8501, Japan.

The interactions of chlorophyll (Chl) and bacteriochlorophyll (BChl) pigments with the polypeptides in photosynthetic light-harvesting proteins are responsible for controlling the absorption energy of (B)Chls in protein matrixes. The binding pocket of B800 BChl a in LH2 proteins, which are peripheral light-harvesting proteins in purple photosynthetic bacteria, is useful for studying such structure-property relationships. We report the reconstitution of Chl f, which has the formyl group at the 2-position, in the B800 cavity of LH2 from the purple bacterium Rhodoblastus acidophilus. Read More

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Human low-density lipoprotein receptor plays an important role in hepatitis B virus infection.

PLoS Pathog 2021 Jul 22;17(7):e1009722. Epub 2021 Jul 22.

Department of Microbiology, University of Alabama at Birmingham School of Medicine, Birmingham, Alabama, United States of America.

Hepatitis B virus (HBV) chronically infects more than 240 million people worldwide, resulting in chronic hepatitis, cirrhosis, and hepatocellular carcinoma. HBV vaccine is effective to prevent new HBV infection but does not offer therapeutic benefit to hepatitis B patients. Neither are current antiviral drugs curative of chronic hepatitis B. Read More

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Aiming for a bull's-eye: Targeting antifungals to fungi with dectin-decorated liposomes.

PLoS Pathog 2021 Jul 22;17(7):e1009699. Epub 2021 Jul 22.

Department of Microbiology, University of Georgia, Athens, Georgia, United States of America.

Globally, there are several million individuals with life-threatening invasive fungal diseases such as candidiasis, aspergillosis, cryptococcosis, Pneumocystis pneumonia (PCP), and mucormycosis. The mortality rate for these diseases generally exceeds 40%. Annual medical costs to treat these invasive fungal diseases in the United States exceed several billion dollars. Read More

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A highly potent and safe pyrrolopyridine-based allosteric HIV-1 integrase inhibitor targeting host LEDGF/p75-integrase interaction site.

PLoS Pathog 2021 Jul 22;17(7):e1009671. Epub 2021 Jul 22.

Department of Pediatrics, School of Medicine, Emory University, Atlanta, Georgia, United States of America.

Allosteric integrase inhibitors (ALLINIs) are a class of experimental anti-HIV agents that target the noncatalytic sites of the viral integrase (IN) and interfere with the IN-viral RNA interaction during viral maturation. Here, we report a highly potent and safe pyrrolopyridine-based ALLINI, STP0404, displaying picomolar IC50 in human PBMCs with a >24,000 therapeutic index against HIV-1. X-ray structural and biochemical analyses revealed that STP0404 binds to the host LEDGF/p75 protein binding pocket of the IN dimer, which induces aberrant IN oligomerization and blocks the IN-RNA interaction. Read More

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A mathematical investigation into the uptake kinetics of nanoparticles in vitro.

PLoS One 2021 22;16(7):e0254208. Epub 2021 Jul 22.

Department for Applied Mathematics, Liverpool John Moores University, Liverpool, United Kingdom.

Nanoparticles have the potential to increase the efficacy of anticancer drugs whilst reducing off-target side effects. However, there remain uncertainties regarding the cellular uptake kinetics of nanoparticles which could have implications for nanoparticle design and delivery. Polymersomes are nanoparticle candidates for cancer therapy which encapsulate chemotherapy drugs. Read More

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Constitutive activation of NF-κB inducing kinase (NIK) in the mesenchymal lineage using Osterix (Sp7)- or Fibroblast-specific protein 1 (S100a4)-Cre drives spontaneous soft tissue sarcoma.

PLoS One 2021 22;16(7):e0254426. Epub 2021 Jul 22.

Musculoskeletal Research Center, Washington University School of Medicine, St. Louis, MO, United States of America.

Aberrant NF-κB signaling fuels tumor growth in multiple human cancer types including both hematologic and solid malignancies. Chronic elevated alternative NF-κB signaling can be modeled in transgenic mice upon activation of a conditional NF-κB-inducing kinase (NIK) allele lacking the regulatory TRAF3 binding domain (NT3). Here, we report that expression of NT3 in the mesenchymal lineage with Osterix (Osx/Sp7)-Cre or Fibroblast-Specific Protein 1 (FSP1)-Cre caused subcutaneous, soft tissue tumors. Read More

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Fission yeast Rad8/HLTF facilitates Rad52-dependent chromosomal rearrangements through PCNA lysine 107 ubiquitination.

PLoS Genet 2021 Jul 22;17(7):e1009671. Epub 2021 Jul 22.

Department of Biological Sciences, Graduate School of Science, Osaka University, Toyonaka, Japan.

Gross chromosomal rearrangements (GCRs), including translocation, deletion, and inversion, can cause cell death and genetic diseases such as cancer in multicellular organisms. Rad51, a DNA strand exchange protein, suppresses GCRs by repairing spontaneous DNA damage through a conservative way of homologous recombination, gene conversion. On the other hand, Rad52 that catalyzes single-strand annealing (SSA) causes GCRs using homologous sequences. Read More

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