4,319 results match your criteria inhibit histone

SMMPPI: a machine learning-based approach for prediction of modulators of protein-protein interactions and its application for identification of novel inhibitors for RBD:hACE2 interactions in SARS-CoV-2.

Brief Bioinform 2021 Apr 12. Epub 2021 Apr 12.

Bioinformatics & Computational Biology research group at NII, New Delhi 110067, India.

Small molecule modulators of protein-protein interactions (PPIs) are being pursued as novel anticancer, antiviral and antimicrobial drug candidates. We have utilized a large data set of experimentally validated PPI modulators and developed machine learning classifiers for prediction of new small molecule modulators of PPI. Our analysis reveals that using random forest (RF) classifier, general PPI Modulators independent of PPI family can be predicted with ROC-AUC higher than 0. Read More

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Epigenetic Treatment of Urothelial Carcinoma Cells Sensitizes to Cisplatin Chemotherapy and PARP Inhibitor Treatment.

Cancers (Basel) 2021 Mar 18;13(6). Epub 2021 Mar 18.

Department of Urology, Medical Faculty, Heinrich-Heine-University Duesseldorf, Moorenstr. 5, 40225 Duesseldorf, Germany.

Muscle-invasive urothelial carcinoma (UC) is treated with cisplatin-based chemotherapy, which is only moderately efficient, mostly due to development of resistance. New therapy approaches are therefore urgently needed. Epigenetic alterations due to frequent mutations in epigenetic regulators contribute to development of the disease and to treatment resistance, and provide targets for novel drug combination therapies. Read More

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Garcinol-A Natural Histone Acetyltransferase Inhibitor and New Anti-Cancer Epigenetic Drug.

Int J Mol Sci 2021 Mar 11;22(6). Epub 2021 Mar 11.

Department of Physiology, Pomeranian Medical University in Szczecin, al. Powstancow Wlkp. 72, 70-111 Szczecin, Poland.

Garcinol extracted from fruit peel and leaves is a polyisoprenylated benzophenone. In traditional medicine it was used for its antioxidant and anti-inflammatory properties. Several studies have shown anti-cancer properties of garcinol in cancer cell lines and experimental animal models. Read More

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Moscatilin Suppresses the Breast Cancer Both In Vitro and In Vivo by Inhibiting HDAC3.

Dose Response 2021 Jan-Mar;19(1):15593258211001251. Epub 2021 Mar 15.

Department of Tumor Surgery, Quanzhou Guangqian Hospital, Meishan Town, Nan'an City, Quanzhou, Fujian, China.

Moscatilin, a natural compound isolated from the orchid , has multiple pharmacological actions. The present study investigated the anti-tumor role of moscatilin in breast cancer and elucidated the underlying mechanisms. Cell proliferation, viability, and apoptosis of moscatilin treated MDA-MB-231 cells were determined by CCK-8 assay and flow cytometry. Read More

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Mesenchymal Stem Cell-Derived Exosomes Carry MicroRNA-125a to Protect Against Diabetic Nephropathy by Targeting Histone Deacetylase 1 and Downregulating Endothelin-1.

Diabetes Metab Syndr Obes 2021 25;14:1405-1418. Epub 2021 Mar 25.

Department of Nephrology, The First People's Hospital of Zigong, Zigong, 643000, Sichuan, People's Republic of China.

Background: Mesenchymal stem cell (MSC)-derived exosomes have seen great advances in human disease control in a minimally invasive manner. This research aimed to explore the function of MSC-derived exosomes in diabetic nephropathy (DN) progression and the molecules involved.

Methods: A rat model with DN and rat glomerular mesangial cell (GMC) models treated with high glucose (HG) were established, which were treated with exosomes from adipose-derived-MSCs (adMSCs). Read More

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A novel histone deacetylase inhibitor LT-548-133-1 induces apoptosis by inhibiting HDAC and interfering with microtubule assembly in MCF-7 cells.

Invest New Drugs 2021 Mar 31. Epub 2021 Mar 31.

School of Life Science and Technology, China Pharmaceutical University, Nanjing, 210009, China.

Many studies have indicated that histone deacetylase inhibitors (HDACis) have a significant antitumor effect in cancer. Here we report a compound named LT-548-133-1 that not only acts as an HDAC inhibitor but also interferes with microtubule assembly to inhibit MCF-7 cell proliferation and induce apoptosis. Consistent with Chidamide, LT-548-133-1 inhibited HDAC activity and increased histone H3 acetylation. Read More

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Discovery of new tranylcypromine derivatives as highly potent LSD1 inhibitors.

Bioorg Med Chem Lett 2021 Mar 26;41:127993. Epub 2021 Mar 26.

School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, China. Electronic address:

Tranylcypromine (TCP)-based structural modifications lead to the discovery of new LSD1 inhibitors, of which compounds 26b and 29b effectively inhibit LSD1 with the IC values of 17 and 11 nM, respectively and also show good selectivity over MAO-B. Mechanistic studies showed that compound 29b concentration-dependently induced H3K4me1/2 accumulation in LSD1 overexpressed MGC-803 cells and also inhibited metastasis of MGC-803 cells. Collectively, both compounds could be promising lead compounds for further investigation. Read More

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The duality of PRDM proteins: epigenetic and structural perspectives.

FEBS J 2021 Mar 28. Epub 2021 Mar 28.

Center for Therapeutics Discovery, Department of Oncological Sciences and Pharmacological Sciences, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, USA.

PRDMs are a subfamily of Kruppel-like zinc finger proteins controlling key processes in metazoan development and in cancer. PRDMs exhibit unique dualities: (i) PR domain/ZNF arrays - their structure combines a SET-like domain known as a PR domain, typically found in methyltransferases, with a variable array of C2H2 zinc fingers (ZNF) characteristic of DNA-binding transcription factors; (ii) Transcriptional activators/repressors - their physiological function is context and cell dependent; mechanistically, some PRDMs have a PKMT activity and directly catalyze histone lysine methylation, while others are rather pseudomethyltransferases and act by recruiting transcriptional co-factors; (iii) Oncogenes/tumor suppressors - their pathological function depends on the specific PRDM isoform expressed during tumorigenesis. This duality is well known as the "Yin and Yang" of PRDMs and involves a complex regulation of alternative splicing or alternative promoter usage, to generate full-length or PR-deficient isoforms with opposing functions in cancer. Read More

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4sc-202 and Ink-128 cooperate to reverse the epithelial to mesenchymal transition in OSCC.

Oral Dis 2021 Mar 27. Epub 2021 Mar 27.

Department of Periodontics, Stomatological Hospital, Southern Medical University, Guangzhou, Guangdong, China.

Treatment of oral squamous cell carcinoma remains a challenge due to a high incidence of treatment resistance, which is followed by tumor recrudescence and metastasis to the lymph nodes. Thus, it is important to explore novel inhibitors of OSCC. Here, we aimed to identify drugs that may cooperate with histone deacetylase inhibitors to reverse the EMT, inhibit EMT and cell migration and invasion, and contribute to therapeutic efficacy. Read More

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Bioinformatics-Based Identification of HDAC Inhibitors as Potential Drugs to Target EGFR Wild-Type Non-Small-Cell Lung Cancer.

Front Oncol 2021 8;11:620154. Epub 2021 Mar 8.

Department of Respiratory and Infectious Disease of Geriatrics, The First Hospital of China Medical University, Shenyang, China.

Patients with EGFR-mutant non-small-cell lung cancer (NSCLC) greatly benefit from EGFR-tyrosine kinase inhibitors (EGFR-TKIs) while the prognosis of patients who lack EGFR-sensitive mutations (EGFR wild type, EGFR-WT) remains poor due to a lack of effective therapeutic strategies. There is an urgent need to explore the key genes that affect the prognosis and develop potentially effective drugs in EGFR-WT NSCLC patients. In this study, we clustered functional modules related to the survival traits of EGFR-WT patients using weighted gene co-expression network analysis (WGCNA). Read More

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Ketamine Inhibits Ovarian Cancer Cell Growth by Regulating the lncRNA-PVT1/EZH2/p57 Axis.

Front Genet 2020 8;11:597467. Epub 2021 Mar 8.

Department of Endocrinology, China-Japan Union Hospital, Jilin University, Changchun, China.

Ketamine is widely used for cancer pain treatment in clinic, and has been shown to inhibit various tumor cells growth. However, the effect of ketamine on ovarian cancer cells growth and the downstream molecules has not been defined. In the present study, we found that ketamine significantly inhibited the proliferation and survival of six ovarian cancer cell lines. Read More

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CircRNA RSF1 regulated ox-LDL induced vascular endothelial cells proliferation, apoptosis and inflammation through modulating miR-135b-5p/HDAC1 axis in atherosclerosis.

Biol Res 2021 Mar 23;54(1):11. Epub 2021 Mar 23.

Department of Cardiology, The Second Hospital of Jilin University, No.218, Ziqiang Street, Nanguan District, Changchun, 130041, Jilin, China.

Background: Atherosclerosis (AS) is the most common type in cardiovascular disease. Due to its complex pathogenesis, the exact etiology of AS is unclear. circRNA has been shown to play an essential role in most diseases. Read More

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Antihypertrophic Memory after Regression of Exercise-induced Physiological Myocardial Hypertrophy is Mediated by the Long Noncoding RNA Mhrt779.

Circulation 2021 Mar 24. Epub 2021 Mar 24.

Department of Cardiology, State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Lab of Shock and Microcirculation, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China; Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory), 510005 Guangzhou, China.

Exercise can induce physiological myocardial hypertrophy (PMH), and former athletes can live 5-6 years longer than nonathletic controls, suggesting a benefit after regression of PMH. We previously reported that regression of pathological myocardial hypertrophy has antihypertrophic effects. Accordingly, we hypothesized that antihypertrophic memory exists even after PMH has regressed, increasing myocardial resistance to subsequent pathological hypertrophic stress. Read More

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HDAC3 protects against atherosclerosis through inhibition of inflammation via the microRNA-19b/PPARγ/NF-κB axis.

Atherosclerosis 2021 Feb 20;323:1-12. Epub 2021 Feb 20.

Department of Cardiology, the Second Hospital of Jilin University, Changchun, 130041, PR China. Electronic address:

Background And Aims: Atherosclerosis (AS) is one of the leading causes of cardiovascular diseases. Studies have revealed critical roles of microRNAs (miRNAs) in the progression of AS. This study was conducted to elucidate the role and mechanism by which miR-19b influences AS. Read More

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February 2021

The histone acetyltransferase HBO1 functions as a novel oncogenic gene in osteosarcoma.

Theranostics 2021 4;11(10):4599-4615. Epub 2021 Mar 4.

Jiangsu Key Laboratory of Neuropsychiatric Diseases and Institute of Neuroscience, Soochow University, Suzhou, China.

HBO1 (KAT7 or MYST2) is a histone acetyltransferase that acetylates H3 and H4 histones. HBO1 expression was tested in human OS tissues and cells. Genetic strategies, including shRNA, CRISPR/Cas9 and overexpression constructs, were applied to exogenously alter HBO1 expression in OS cells. Read More

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Synergistic efficacy of curcumin and anti-programmed cell death-1 in hepatocellular carcinoma.

Life Sci 2021 Mar 19:119359. Epub 2021 Mar 19.

Department of Hepatology, Qingdao No. 6 People's Hospital, Qingdao 266033, PR China. Electronic address:

Hepatocellular carcinoma (HCC) ranks near the top in the global list of malignancies causing cancer-related death. Recently, combination therapy has gained popularity in treating this cancer. We tried to investigate the efficacy of combined treatment with curcumin and anti-programmed cell death-1 (anti-PD-1) in HCC. Read More

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HDAC2 interacts with microRNA-503-5p to regulate SGK1 in osteoarthritis.

Arthritis Res Ther 2021 03 9;23(1):78. Epub 2021 Mar 9.

Department of Orthopaedics, The First Affiliated Hospital of Zhengzhou University, No. 1, Eastern Jianshe Road, Zhengzhou, 450000, Henan Province, People's Republic of China.

Background: Osteoarthritis (OA) is a disabling joint disease that causes articular cartilage degeneration. It has been implicated that altered expression of histone deacetylase 2 (HDAC2) is found in patients with OA. However, the specific role of HDAC2 in the development of OA still remains enigmatic. Read More

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Modulation of neutrophil (dys)function by Ayurvedic herbs and its potential influence on SARS-CoV-2 infection.

J Ayurveda Integr Med 2021 Mar 16. Epub 2021 Mar 16.

Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal-576104, India.

For centuries, traditional medicines of Ayurveda have been in use to manage infectious and non-infectious diseases. The key embodiment of traditional medicines is the holistic system of approach in the management of human diseases. SARS-CoV-2 (COVID-19) infection is an ongoing pandemic, which has emerged as the major health threat worldwide and is causing significant stress, morbidity and mortality. Read More

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Uhrf1 regulates H3K9me2 modification of mTOR to inhibit the effect of autophagy in myocardial ischemia-reperfusion injury.

Aging (Albany NY) 2021 Mar 19;13. Epub 2021 Mar 19.

Department of Histology and Embryology, College of Basic Medicine, Harbin Medical University, Harbin 150081, China.

The regulation of mTOR and the dimethylation of histone H3 on lysine 9 (H3K9me2) H3K9me2 by Uhrf1 and the mechanism of autophagy regulation in myocardial ischemia-reperfusion injury (MIRI) were studied and . An I/R injury model was established using the primary mouse cardiomyocytes treated with HO. Subsequent analysis by qRT-PCR, western blot, and immunofluorescence indicated that overexpression of Uhrf1 significantly inhibited apoptosis of the HO-treated cardiomyocytes, reduced expression of apoptosis factors caspase-3 and Bax, and increased expression of apoptosis inhibitory factor Bcl-2. Read More

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Epigenetic evidence of an Ac/Dc axis by VPA and SAHA.

Clin Epigenetics 2021 Mar 20;13(1):58. Epub 2021 Mar 20.

Baker Heart and Diabetes Institute, Melbourne, VIC, 3004, Australia.

Background: Valproic acid (VPA) is one of the most commonly used anti-epileptic drugs with pharmacological actions on GABA and blocking voltage-gated ion channels. VPA also inhibits histone deacetylase (HDAC) activity. Suberoylanilide hydroxamic acid is also a member of a larger class of compounds that inhibit HDACs. Read More

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Targeting KDM4A epigenetically activates tumor-cell-intrinsic immunity by inducing DNA replication stress.

Mol Cell 2021 Mar 11. Epub 2021 Mar 11.

Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA 90095, USA; Laboratory of Molecular Signaling, Division of Oral Biology and Medicine, School of Dentistry, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Bioengineering, Henry Samueli School of Engineering and Applied Science, University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address:

Developing strategies to activate tumor-cell-intrinsic immune response is critical for improving tumor immunotherapy by exploiting tumor vulnerability. KDM4A, as a histone H3 lysine 9 trimethylation (H3K9me3) demethylase, has been found to play a critical role in squamous cell carcinoma (SCC) growth and metastasis. Here we report that KDM4A inhibition promoted heterochromatin compaction and induced DNA replication stress, which elicited antitumor immunity in SCC. Read More

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JMJD3-regulated expression of IL-6 is involved in the proliferation and chemosensitivity of acute myeloid leukemia cells.

Biol Chem 2020 Mar 19. Epub 2020 Mar 19.

Department of Hematology, The Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen518107, China.

Emerging evidence shows that histone modification and its related regulators are involved in the progression and chemoresistance of multiple tumors including acute myeloid leukemia cells (AML). Our present study found that the expression of histone lysine demethylase Jumonji domain containing-3 (JMJD3) was increased in AML cells as compared with that in human primary bone marrow (HPBM) cells. Knockdown of JMJD3 can decrease the proliferation of AML cells and increase the chemosensitivity of daunorubicin (DNR) and cytarabine (Ara-C). Read More

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Evaluation of 5-(Trifluoromethyl)-1,2,4-oxadiazole-Based Class IIa HDAC Inhibitors for Huntington's Disease.

ACS Med Chem Lett 2021 Mar 11;12(3):380-388. Epub 2021 Feb 11.

CHDI Management/CHDI Foundation Inc., 6080 Center Drive, Suite 700, Los Angeles, California 90045, United States.

Using an iterative structure-activity relationship driven approach, we identified a CNS-penetrant 5-(trifluoromethyl)-1,2,4-oxadiazole (TFMO, ) with a pharmacokinetic profile suitable for probing class IIa histone deacetylase (HDAC) inhibition in vivo. Given the lack of understanding of endogenous class IIa HDAC substrates, we developed a surrogate readout to measure compound effects in vivo, by exploiting the >100-fold selectivity compound exhibits over class I/IIb HDACs. We achieved adequate brain exposure with compound in mice to estimate a class I/IIb deacetylation EC, using class I substrate H4K12 acetylation and global acetylation levels as a pharmacodynamic readout. Read More

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Surface modification of electrospun fibers with mechano-growth factor for mitigating the foreign-body reaction.

Bioact Mater 2021 Sep 1;6(9):2983-2998. Epub 2021 Mar 1.

Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing, 100083, PR China.

The implantation of synthetic polymeric scaffolds induced foreign-body reaction (FBR) seriously influence the wound healing and impair functionality recovery. A novel short peptide, mechano-growth factor (MGF), was introduced in this study to modify an electrospun polycaprolactone (PCL) fibrous scaffold to direct the macrophage phenotype transition and mitigate the FBR. studies discovered the cell signal transduction mechanism of MGF regulates the macrophage polarization via the expression of related genes and proteins. Read More

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September 2021

The Roles of the Histone Protein Modifier EZH2 in the Uterus and Placenta.

Epigenomes 2020 Sep 2;4(3). Epub 2020 Sep 2.

Department of Physiological Sciences, University of Florida, Gainesville, FL 32610-0144, USA.

Epigenetic modifications regulate normal physiological, as well as pathological processes in various organs, including the uterus and placenta. Both organs undergo dramatic and rapid restructuring that depends upon precise orchestration of events. Epigenetic changes that alter transcription and translation of gene-sets regulate such responses. Read More

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September 2020

Inhibition of PAD4 enhances radiosensitivity and inhibits aggressive phenotypes of nasopharyngeal carcinoma cells.

Cell Mol Biol Lett 2021 Mar 16;26(1). Epub 2021 Mar 16.

Department of Oncology, The Second Nanning People's Hospital, No.13 Dancun Road, Jiangnan District, Nanning, 530031, Guangxi, China.

Background: Nasopharyngeal carcinoma (NPC) is a tumor deriving from nasopharyngeal epithelium. Peptidyl-arginine deiminase 4 (PAD4) is a vital mediator of histone citrullination and plays an essential role in regulating disease process. Radiotherapy is an essential method to treat NPC. Read More

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Targeting Histone Modifications in Bone and Lung Metastatic Cancers.

Curr Osteoporos Rep 2021 Mar 15. Epub 2021 Mar 15.

Graduate Program in Cancer Biology, Vanderbilt University, 2215b Garland Ave, 1165C Medical Research Building IV, Nashville, TN, 37232, USA.

Purpose Of Review: Breast cancer frequently metastasizes to the bone and lung, but the ability to treat metastatic tumor cells remains a pressing clinical challenge. Histone deacetylases (HDACs) and histone acetyltransferases (HATs) have emerged as promising targets since these enzymes are aberrantly expressed in numerous cancers and regulate the expression of genes that drive tumorigenesis and metastasis. This review focuses on the abnormal expression of histone-modifying enzymes in cancers that have a high tropism for the bone and lung and explores the clinical use of histone deacetylase inhibitors for the treatment and prevention of metastasis to these sites. Read More

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EZH2-miRNA Positive Feedback Promotes Tumor Growth in Ovarian Cancer.

Front Oncol 2020 25;10:608393. Epub 2021 Feb 25.

Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Enhancer of zester homolog 2 (EZH2), a histone methyl transferase that mediates H3K27me3 through polycomb repressive complex 2 (PRC2), is overexpressed in ovarian cancer and promotes malignant proliferation. However, the underlying mechanism of maintaining high EZH2 expression remains elusive. Here we showed that microRNA(miRNA) inhibited EZH2 by binding to the 3'-UTR of EZH2 mRNA; conversely, EZH2 can inhibit miRNA expression. Read More

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February 2021

The effects of histone crotonylation and bromodomain protein 4 on prostate cancer cell lines.

Transl Androl Urol 2021 Feb;10(2):900-914

Department of Urology, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.

Background: The aims of this study were to detect the level of histone crotonylation in prostate cancer (PCa) tissues, analyze the correlations between its level and clinical stage and grade, and explore the effects of bromodomain-containing protein 4 (BRD4) inhibitors and sodium crotonate on the histone crotonylation in PCa cell lines and on the functions of PCa cells.

Methods: PCa tissues from 72 patients and adjacent tissues from 7 patients were collected, and immunohistochemistry was used to measure the level of histone crotonylation. Three human PCa cell lines, PC-3, LNCaP, and C42B, were selected and treated with IC50 value of I-BET762, I-BET726, and CPI-203, respectively. Read More

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February 2021

Dissecting the Role of BET Bromodomain Proteins BRD2 and BRD4 in Human NK Cell Function.

Front Immunol 2021 26;12:626255. Epub 2021 Feb 26.

Botnar Research Center, Nuffield Department of Orthopedics, Rheumatology and Musculoskeletal Sciences, National Institute of Health Research Oxford Biomedical Research Unit (BRU), University of Oxford, Oxford, United Kingdom.

Natural killer (NK) cells are innate lymphocytes that play a pivotal role in the immune surveillance and elimination of transformed or virally infected cells. Using a chemo-genetic approach, we identify BET bromodomain containing proteins BRD2 and BRD4 as central regulators of NK cell functions, including direct cytokine secretion, NK cell contact-dependent inflammatory cytokine secretion from monocytes as well as NK cell cytolytic functions. We show that both BRD2 and BRD4 control inflammatory cytokine production in NK cells isolated from healthy volunteers and from rheumatoid arthritis patients. Read More

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February 2021