Product References
Methyl-β-cyclodextrin inhibits EV-D68 virus entry by perturbing the accumulation of virus particles and ICAM-5 in lipid rafts.
Antiviral research
Jiang Y,Liu S,Shen S,Guo H,Huang H,Wei W
Enterovirus D68 (EV-D68) is a member of the Picornavirus family and a causative agent of respiratory diseases in children. The incidence of EV-D68 infection has increased worldwide in recent years. Thus far, there are no approved antiviral agents or vaccines for EV-D68. Here, we show that methyl-β-cyclodextrin (MβCD), a common drug that disrupts lipid rafts, specifically inhibits EV-D68 infection without producing significant cytotoxicity at virucidal concentrations. The addition of ex
Wed Apr 01 00:00:00 EDT 2020
Cdk8 is required for establishment of H3K27me3 and gene repression by Xist and mouse development.
Development (Cambridge, England)
Postlmayr A,Dumeau CE,Wutz A
Thu Jun 11 00:00:00 EDT 2020
Ablation of conceptus PTGS2 expression does not alter early conceptus development and establishment of pregnancy in the pig†.
Biology of reproduction
Pfeiffer CA,Meyer AE,Brooks KE,Chen PR,Milano-Foster J,Spate LD,Benne JA,Cecil RF,Samuel MS,Ciernia LA,Spinka CM,Smith MF,Wells KD,Spencer TE,Prather RS,Geisert RD
Pig conceptuses secrete estrogens (E2), interleukin 1 beta 2 (IL1B2), and prostaglandins (PG) during the period of rapid trophoblast elongation and establishment of pregnancy. Previous studies established that IL1B2 is essential for rapid conceptus elongation, whereas E2 is not essential for conceptus elongation or early maintenance of the corpora lutea. The objective of the present study was to determine if conceptus expression of prostaglandin-endoperoxide synthase 2 (PTGS2) and release of PG
Fri Feb 14 00:00:00 EST 2020
Aberrantly expressed HORMAD1 disrupts nuclear localization of MCM8-MCM9 complex and compromises DNA mismatch repair in cancer cells.
Cell death & disease
Liu K,Wang Y,Zhu Q,Li P,Chen J,Tang Z,Shen Y,Cheng X,Lu LY,Liu Y
Thu Jul 09 00:00:00 EDT 2020
Targeting VE-PTP phosphatase protects the kidney from diabetic injury.
The Journal of experimental medicine
Carota IA,Kenig-Kozlovsky Y,Onay T,Scott R,Thomson BR,Souma T,Bartlett CS,Li Y,Procissi D,Ramirez V,Yamaguchi S,Tarjus A,Tanna CE,Li C,Eremina V,Vestweber D,Oladipupo SS,Breyer MD,Quaggin SE
Diabetic nephropathy is a leading cause of end-stage kidney failure. Reduced angiopoietin-TIE2 receptor tyrosine kinase signaling in the vasculature leads to increased vascular permeability inflammation and endothelial cell loss and is associated with the development of diabetic complications. Here we identified a mechanism to explain how TIE2 signaling is attenuated in diabetic animals. Expression of vascular endothelial protein tyrosine phosphatase VE-PTP (also known as PTPRB) which dephosphor
Mon Apr 01 00:00:00 EDT 2019
MicroRNA‑132 mediates proliferation and migration of pulmonary smooth muscle cells via targeting PTEN.
Molecular medicine reports
Zeng ZH,Wu WH,Peng Q,Sun YH,Liu JX
Pulmonary arterial hypertension (PAH) is a severe and progressive disease characterized by the remodeling of small pulmonary arteries. The aberrant proliferation of pulmonary arterial smooth muscle cells (PASMCs) is the primary feature of PAH. MicroRNA (miR)‚132 has been demonstrated to inhibit the proliferation of vascular smooth muscle cells and repress neointimal formation. Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a direct target of miR‚132 that has b
Wed May 01 00:00:00 EDT 2019
BAP1 complex promotes transcription by opposing PRC1-mediated H2A ubiquitylation.
Nature communications
Campagne A,Lee MK,Zielinski D,Michaud A,Le Corre S,Dingli F,Chen H,Shahidian LZ,Vassilev I,Servant N,Loew D,Pasmant E,Postel-Vinay S,Wassef M,Margueron R
In Drosophila a complex consisting of Calypso and ASX catalyzes H2A deubiquitination and has been reported to act as part of the Polycomb machinery in transcriptional silencing. The mammalian homologs of these proteins (BAP1 and ASXL1/2/3 respectively) are frequently mutated in various cancer types yet their precise functions remain unclear. Using an integrative approach based on isogenic cell lines generated with CRISPR/Cas9 we uncover an unanticipated role for BAP1 in gene activation. This fun
Mon Jan 21 00:00:00 EST 2019
Temporal Control of the TGF-β Signaling Network by Mouse ESC MicroRNA Targets of Different Affinities.
Cell reports
Kelly TJ,Brümmer A,Hooshdaran N,Tariveranmoshabad M,Zamudio JR
Although microRNAs (miRNAs) function in the control of embryonic stem cell (ESC) pluripotency, a systems-level understanding is still being developed. Through the analysis of progressive Argonaute (Ago)-miRNA depletion and rescue, including stable Ago knockout mouse ESCs, we uncover transforming growth factor beta (TGF-β) pathway activation as a direct and early response to ESC miRNA reduction. Mechanistically, we link the derepression of weaker miRNA targets, including TGF-β receptor
Tue Nov 26 00:00:00 EST 2019
A second open reading frame in human enterovirus determines viral replication in intestinal epithelial cells.
Nature communications
Guo H,Li Y,Liu G,Jiang Y,Shen S,Bi R,Huang H,Cheng T,Wang C,Wei W
Human enteroviruses (HEVs) of the family Picornaviridae, which comprises non-enveloped RNA viruses, are ubiquitous worldwide. The majority of EV proteins are derived from viral polyproteins encoded by a single open reading frame (ORF). Here, we characterize a second ORF in HEVs that is crucial for viral intestinal infection. Disruption of ORF2p expression decreases the replication capacity of EV-A71 in human intestinal epithelial cells (IECs). Ectopic expression of ORF2p proteins derived from di
Fri Sep 06 00:00:00 EDT 2019
Warfarin and vitamin K epoxide reductase: a molecular accounting for observed inhibition.
Blood
Wu S,Chen X,Jin DY,Stafford DW,Pedersen LG,Tie JK
Vitamin K epoxide reductase (VKOR) an endoplasmic reticulum membrane protein is the key enzyme for vitamin K-dependent carboxylation a posttranslational modification that is essential for the biological functions of coagulation factors. VKOR is the target of the most widely prescribed oral anticoagulant warfarin. However the topological structure of VKOR and the mechanism of warfarin's inhibition of VKOR remain elusive. Additionally it is not clear why warfarin-resistant VKOR mutations identifie
Thu Aug 09 00:00:00 EDT 2018
Porcine parvovirus infection impairs progesterone production in luteal cells through mitogen-activated protein kinases, p53, and mitochondria-mediated apoptosis.
Biology of reproduction
Zhang L,Wang Z,Zhang J,Luo X,Du Q,Chang L,Zhao X,Huang Y,Tong D
Porcine parvovirus (PPV) is a major virus that leads to fetal death in swine. However the effects of PPV infection on sows are poorly understood. The aim of this study was to investigate the effects of PPV on porcine steroidogenic luteal cells (SLCs) survival and functions and underlying mechanisms. In vivo experiment results showed that artificial infection of PPV significantly reduced the concentration of serum progesterone and induced histopathological lesions and SLCs apoptosis in porcine co
Sun Apr 01 00:00:00 EDT 2018
SETDB2 Links E2A-PBX1 to Cell-Cycle Dysregulation in Acute Leukemia through CDKN2C Repression.
Cell reports
Lin CH,Wong SH,Kurzer JH,Schneidawind C,Wei MC,Duque-Afonso J,Jeong J,Feng X,Cleary ML
Acute lymphoblastic leukemia (ALL) is associated with significant morbidity and mortality, necessitating further improvements in diagnosis and therapy. Targeted therapies directed against chromatin regulators are emerging as promising approaches in preclinical studies and early clinical trials. Here, we demonstrate an oncogenic role for the protein lysine methyltransferase SETDB2 in leukemia pathogenesis. It is overexpressed in pre-BCR+ ALL and required for their maintenance in vitro and in
Tue Apr 24 00:00:00 EDT 2018
Noncanonical function of DGCR8 controls mESC exit from pluripotency.
The Journal of cell biology
Cirera-Salinas D,Yu J,Bodak M,Ngondo RP,Herbert KM,Ciaudo C
Mouse embryonic stem cells (mESCs) deficient for DGCR8 a key component of the microprocessor complex present strong differentiation defects. However the exact reasons impairing their commitment remain elusive. The analysis of newly generated mutant mESCs revealed that DGCR8 is essential for the exit from the pluripotency state. To dissociate canonical versus noncanonical functions of DGCR8 we complemented the mutant mESCs with a phosphomutant DGCR8 which restored microRNA levels but did not resc
Wed Feb 01 00:00:00 EST 2017
UHRF2 regulates local 5-methylcytosine and suppresses spontaneous seizures.
Epigenetics
Liu Y,Zhang B,Meng X,Korn MJ,Parent JM,Lu LY,Yu X
The 5-methylcytosine (5mC) modification regulates multiple cellular processes and is faithfully maintained following DNA replication. In addition to DNA methyltransferase (DNMT) family proteins, ubiquitin-like PHD and ring finger domain-containing protein 1 (UHRF1) plays an important role in the maintenance of 5mC levels. Loss of UHRF1 abolishes 5mC in cells and leads to embryonic lethality in mice. Interestingly, UHRF1 has a paralog, UHRF2, that has similar sequence and domain architecture, but
Mon Jul 03 00:00:00 EDT 2017
Post-translational modifications of Annexin A2 are linked to its association with perinuclear nonpolysomal mRNP complexes.
FEBS open bio
Aukrust I,Rosenberg LA,Ankerud MM,Bertelsen V,Hollås H,Saraste J,Grindheim AK,Vedeler A
Various post-translational modifications (PTMs) regulate the localisation and function of the multifunctional protein Annexin A2 (AnxA2). In addition to its various tasks as a cytoskeletal- and membrane-associated protein AnxA2 can function as a -acting protein binding to -acting sequences of specific mRNAs. In the present study we have examined the role of Ser25 phosphorylation in subcellular localisation of AnxA2 and its interaction with mRNP complexes. Subcellular fractionation and confocal m
Wed Feb 01 00:00:00 EST 2017
Transcription Factor EB Is Selectively Reduced in the Nuclear Fractions of Alzheimer's and Amyotrophic Lateral Sclerosis Brains.
Neuroscience journal
Wang H,Wang R,Xu S,Lakshmana MK
Multiple studies suggest that autophagy is strongly dysregulated in Alzheimer's disease (AD) and amyotrophic lateral sclerosis (ALS), as evidenced by accumulation of numerous autophagosomes, lysosomes with discontinuous membranes, and aggregated proteins in the patients' brains. Transcription factor EB (TFEB) was recently discovered to be a master regulator of lysosome biogenesis and autophagy. To examine whether aberrant autophagy in AD and ALS is due to alterations in TFEB expression, we syste
Tue Jul 19 00:00:00 EDT 2016
Extracellular vesicles released from cells exposed to reactive oxygen species increase annexin A2 expression and survival of target cells exposed to the same conditions.
Communicative & integrative biology
Grindheim AK,Vedeler A
Annexin A2 (AnxA2) is present in multiple cellular compartments and interacts with numerous ligands including calcium, proteins, cholesterol, negatively charged phospholipids and RNA. These interactions are tightly regulated by its post-translational modifications. The levels of AnxA2 and its Tyr23 phosphorylated form (pTyr23AnxA2) are increased in many cancers and the protein is involved in malignant cell transformation, metastasis and angiogenesis. Our previous studies of rat pheochromocytoma
Tue Aug 30 00:00:00 EDT 2016
Zinc Finger Protein 618 Regulates the Function of UHRF2 (Ubiquitin-like with PHD and Ring Finger Domains 2) as a Specific 5-Hydroxymethylcytosine Reader.
The Journal of biological chemistry
Liu Y,Zhang B,Kuang H,Korakavi G,Lu LY,Yu X
5-Hydroxymethylcytosine (5hmC) is an epigenetic modification that is generated by ten-eleven translocation (TET) protein-mediated oxidation of 5-methylcytosine (5mC). 5hmC is associated with transcription regulation and is decreased in many cancers including melanoma. Accumulating evidence has suggested that 5hmC is functionally distinct from 5mC. Ubiquitin-like with PHD and ring finger domains 2 (UHRF2) is the first known specific 5hmC reader that has higher affinity to 5hmC than 5mC, suggestin
Fri Jun 24 00:00:00 EDT 2016
Epigenetic roles of MLL oncoproteins are dependent on NF-κB.
Cancer cell
Kuo HP,Wang Z,Lee DF,Iwasaki M,Duque-Afonso J,Wong SH,Lin CH,Figueroa ME,Su J,Lemischka IR,Cleary ML
MLL fusion proteins in leukemia induce aberrant transcriptional elongation and associated chromatin perturbations; however, the upstream signaling pathways and activators that recruit or retain MLL oncoproteins at initiated promoters are unknown. Through functional and comparative genomic studies, we identified an essential role for NF-κB signaling in MLL leukemia. Suppression of NF-κB led to robust antileukemia effects that phenocopied loss of functional MLL oncoprotein or associate
Mon Oct 14 00:00:00 EDT 2013
Complete and unidirectional conversion of human embryonic stem cells to trophoblast by BMP4.
Proceedings of the National Academy of Sciences of the United States of America
Amita M,Adachi K,Alexenko AP,Sinha S,Schust DJ,Schulz LC,Roberts RM,Ezashi T
Human ES cells (hESC) exposed to bone morphogenic protein 4 (BMP4) in the absence of FGF2 have become widely used for studying trophoblast development, but the soundness of this model has been challenged by others, who concluded that differentiation was primarily toward mesoderm rather than trophoblast. Here we confirm that hESC grown under the standard conditions on a medium conditioned by mouse embryonic fibroblasts in the presence of BMP4 and absence of FGF2 on a Matrigel substratum rapidly c
Tue Mar 26 00:00:00 EDT 2013
Inhibitory and combinatorial effect of diphyllin, a v-ATPase blocker, on influenza viruses.
Antiviral research
Chen HW,Cheng JX,Liu MT,King K,Peng JY,Zhang XQ,Wang CH,Shresta S,Schooley RT,Liu YT
An influenza pandemic poses a serious threat to humans and animals. Conventional treatments against influenza include two classes of pathogen-targeting antivirals: M2 ion channel blockers (such as amantadine) and neuraminidase inhibitors (such as oseltamivir). Examination of the mechanism of influenza viral infection has shown that endosomal acidification plays a major role in facilitating the fusion between viral and endosomal membranes. This pathway has led to investigations on vacuolar ATPase
Sun Sep 01 00:00:00 EDT 2013
Role of RanBP9 on amyloidogenic processing of APP and synaptic protein levels in the mouse brain.
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
Lakshmana MK,Hayes CD,Bennett SP,Bianchi E,Reddy KM,Koo EH,Kang DE
We previously reported that RanBP9 binds low-density lipoprotein receptor-related protein (LRP), amyloid precursor protein (APP), and BACE1 and robustly increased Aβ generation in a variety of cell lines and primary neuronal cultures. To confirm the physiological/ pathological significance of this phenotype in vivo, we successfully generated transgenic mice overexpressing RanBP9 as well as RanBP9-null mice. Here we show that RanBP9 overexpression resulted in >2-fold increase in Aβ40
Tue May 01 00:00:00 EDT 2012