Product References
Influenza Virus Z-RNAs Induce ZBP1-Mediated Necroptosis.
Cell
Zhang T,Yin C,Boyd DF,Quarato G,Ingram JP,Shubina M,Ragan KB,Ishizuka T,Crawford JC,Tummers B,Rodriguez DA,Xue J,Peri S,Kaiser WJ,López CB,Xu Y,Upton JW,Thomas PG,Green DR,Balachandran S
Thu Mar 19 00:00:00 UTC 2020
Germline Mutations in FAF1 Are Associated With Hereditary Colorectal Cancer.
Gastroenterology
Bonjoch L,Franch-Expósito S,Garre P,Belhadj S,Muñoz J,Arnau-Collell C,Díaz-Gay M,Gratacós-Mulleras A,Raimondi G,Esteban-Jurado C,Soares de Lima Y,Herrera-Pariente C,Cuatrecasas M,Ocaña T,Castells A,Fillat C,Capellá G,Balaguer F,Caldés T,Valle L,Castellví-Bel S
objective: A significant proportion of colorectal cancer (CRC) cases have familial aggregation but little is known about the genetic factors that contribute to these cases. We performed an exhaustive functional characterization of genetic variants associated with familial CRC. methods: We performed whole-exome sequencing analyses of 75 patients from 40 families with a history of CRC (including early-onset cases) of an unknown germline basis (discovery cohort). We also sequenced specific genes in
Wed Jul 01 00:00:00 UTC 2020
Pathogenic Variants in CEP85L Cause Sporadic and Familial Posterior Predominant Lissencephaly.
Neuron
Tsai MH,Muir AM,Wang WJ,Kang YN,Yang KC,Chao NH,Wu MF,Chang YC,Porter BE,Jansen LA,Sebire G,Deconinck N,Fan WL,Su SC,Chung WH,Almanza Fuerte EP,Mehaffey MG,Ng CC,Chan CK,Lim KS,Leventer RJ,Lockhart PJ,Riney K,Damiano JA,Hildebrand MS,Mirzaa GM,Dobyns WB,Berkovic SF,Scheffer IE,Tsai JW,Mefford HC
Lissencephaly (LIS), denoting a "smooth brain," is characterized by the absence of normal cerebral convolutions with abnormalities of cortical thickness. Pathogenic variants in over 20 genes are associated with LIS. The majority of posterior predominant LIS is caused by pathogenic variants in LIS1 (also known as PAFAH1B1), although a significant fraction remains without a known genetic etiology. We now implicate CEP85L as an important cause of posterior predominant LIS, identifying 13
Wed Apr 22 00:00:00 UTC 2020
CPEB3-mediated MTDH mRNA translational suppression restrains hepatocellular carcinoma progression.
Cell death & disease
Zhang H,Zou C,Qiu Z,E F,Li Q,Chen M,Wang D,Tan Q,Yin W,Matunda C,Wang H,Zhang Y,Zhan C,Wang C,Wu Y,Xuan X,Wang Y,Zou C,Lv G,Gao X
Wed Sep 23 00:00:00 UTC 2020
Nuclear moonlighting of cytosolic glyceraldehyde-3-phosphate dehydrogenase regulates Arabidopsis response to heat stress.
Nature communications
Kim SC,Guo L,Wang X
Fri Jul 10 00:00:00 UTC 2020
Integrative functional genomics decodes herpes simplex virus 1.
Nature communications
Whisnant AW,Jürges CS,Hennig T,Wyler E,Prusty B,Rutkowski AJ,L'hernault A,Djakovic L,Göbel M,Döring K,Menegatti J,Antrobus R,Matheson NJ,Künzig FWH,Mastrobuoni G,Bielow C,Kempa S,Liang C,Dandekar T,Zimmer R,Landthaler M,Grässer F,Lehner PJ,Friedel CC,Erhard F,Dölken L
The predicted 80 open reading frames (ORFs) of herpes simplex virus 1 (HSV-1) have been intensively studied for decades. Here, we unravel the complete viral transcriptome and translatome during lytic infection with base-pair resolution by computational integration of multi-omics data. We identify a total of 201 transcripts and 284 ORFs including all known and 46 novel large ORFs. This includes a so far unknown ORF in the locus deleted in the FDA-approved oncolytic virus Imlygic. Multiple transcr
Mon Apr 27 00:00:00 UTC 2020
Disease-Causing Mutations in SF3B1 Alter Splicing by Disrupting Interaction with SUGP1.
Molecular cell
Zhang J,Ali AM,Lieu YK,Liu Z,Gao J,Rabadan R,Raza A,Mukherjee S,Manley JL
SF3B1, which encodes an essential spliceosomal protein, is frequently mutated in myelodysplastic syndromes (MDS) and many cancers. However, the defect of mutant SF3B1 is unknown. Here, we analyzed RNA sequencing data from MDS patients and confirmed that SF3B1 mutants use aberrant 3' splice sites. To elucidate the underlying mechanism, we purified complexes containing either wild-type or the hotspot K700E mutant SF3B1 and found that levels of a poorly studied spliceosomal protein, SUGP1, were red
Thu Oct 03 00:00:00 UTC 2019
Interaction and Regulation Between Lipid Mediator Phosphatidic Acid and Circadian Clock Regulators.
The Plant cell
Kim SC,Nusinow DA,Sorkin ML,Pruneda-Paz J,Wang X
Circadian clocks play important roles in regulating cellular metabolism but the reciprocal effect that metabolism has on the clock is largely unknown in plants. Here we show that the central glycerolipid metabolite and lipid mediator phosphatidic acid (PA) interacts with and modulates the function of the core clock regulators LATE ELONGATED HYPOCOTYL (LHY) and CIRCADIAN CLOCK ASSOCIATED1 (CCA1) in Arabidopsis (). PA reduced the ability of LHY and CCA1 to bind the promoter of their target gene I
Fri Feb 01 00:00:00 UTC 2019
PARP1 Suppresses the Transcription of PD-L1 by Poly(ADP-Ribosyl)ating STAT3.
Cancer immunology research
Ding L,Chen X,Xu X,Qian Y,Liang G,Yao F,Yao Z,Wu H,Zhang J,He Q,Yang B
Studies have pointed to a role of PARP1 in regulating gene expression through poly(ADP-ribosyl)ating sequence-specific DNA-binding transcription factors. However few examples exist that link this role of PARP1 to the immunogenicity of cancer cells. Here we report that PARP1 poly(ADP-ribosyl)ates STAT3 and subsequently promotes STAT3 dephosphorylation resulting in reduced transcriptional activity of STAT3 and expression of PD-L1. In this study we showed that PARP1 silencing or pharmacologic inhib
Tue Jan 01 00:00:00 UTC 2019
The Kaposi's Sarcoma-Associated Herpesvirus ORF34 Protein Interacts and Stabilizes HIF-2α via Binding to the HIF-2α bHLH and PAS Domains.
Journal of virology
Haque M,Kousoulas KG
Hypoxia and hypoxia inducible factors (HIFs) play important roles in the Kaposi's sarcoma-associated herpesvirus (KSHV) life cycle. KSHV is the causative agents of Kaposi's sarcoma (KS) and other AIDS related malignancies. Kaposi's sarcoma is a highly vascular tumor which preferentially develops in the lower extremities of the body where blood vessels are often poorly oxygenated. The main cellular responses to hypoxia are mediated mainly by two isoforms of HIF HIF-1α and HIF-2α. Both
Sun Sep 01 00:00:00 UTC 2019
Identification of NMS-873, an allosteric and specific p97 inhibitor, as a broad antiviral against both influenza A and B viruses.
European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences
Zhang J,Hu Y,Hau R,Musharrafieh R,Ma C,Zhou X,Chen Y,Wang J
Influenza virus infection causes substantial morbidity and mortality worldwide. The limited efficacy of oseltamivir in delayed treatment coupled with the increasing incidences of oseltamivir-resistant strains calls for next-generation of antiviral drugs. In this study we discovered NMS-873 an allosteric and specific p97 inhibitor as a broad-spectrum influenza antiviral through forward chemical genomics screening. NMS-873 shows potent antiviral activity with low-nanomolar ECs against multiple hum
Wed May 15 00:00:00 UTC 2019
Congenital goitrous hypothyroidism is caused by dysfunction of the iodide transporter SLC26A7.
Communications biology
Ishii J,Suzuki A,Kimura T,Tateyama M,Tanaka T,Yazawa T,Arimasu Y,Chen IS,Aoyama K,Kubo Y,Saitoh S,Mizuno H,Kamma H
Iodide transport and storage in the thyroid follicles is crucial for thyroid hormone synthesis. Pendrin the iodide exporter that transports iodide to thyroid follicles is responsible for Pendred syndrome a disorder characterized by congenital hypothyroidism and hearing loss. However thyroid hormone levels are basically normal in patients with Pendred syndrome indicating the presence of another unknown iodide transporter. Here we show that SLC26A7 is a novel iodide transporter in the thyroid. We
Tue May 05 00:00:00 UTC 2020
UPF1/SMG7-dependent microRNA-mediated gene regulation.
Nature communications
Park J,Seo JW,Ahn N,Park S,Hwang J,Nam JW
The stability and quality of metazoan mRNAs are under microRNA (miRNA)-mediated and nonsense-mediated control. Although UPF1, a core mediator of nonsense-mediated mRNA decay (NMD), mediates the decay of target mRNA in a 3'UTR-length-dependent manner, the detailed mechanism remains unclear. Here, we suggest that 3'UTR-length-dependent mRNA decay is not mediated by nonsense mRNAs but rather by miRNAs that downregulate target mRNAs via Ago-associated UPF1/SMG7. Global analyses of mRNAs in response
Fri Sep 13 00:00:00 UTC 2019
The Bromodomain Protein 4 Contributes to the Regulation of Alternative Splicing.
Cell reports
Uppal S,Gegonne A,Chen Q,Thompson PS,Cheng D,Mu J,Meerzaman D,Misra HS,Singer DS
The bromodomain protein 4 (BRD4) is an atypical kinase and histone acetyl transferase (HAT) that binds to acetylated histones and contributes to chromatin remodeling and early transcriptional elongation. During transcription, BRD4 travels with the elongation complex. Since most alternative splicing events take place co-transcriptionally, we asked if BRD4 plays a role in regulating alternative splicing. We report that distinct patterns of alternative splicing are associated with a conditional del
Tue Nov 19 00:00:00 UTC 2019
A Chaperone Lid Ensures Efficient and Privileged Client Transfer during Tail-Anchored Protein Targeting.
Cell reports
Chio US,Chung S,Weiss S,Shan SO
Molecular chaperones play key roles in maintaining cellular proteostasis. In addition to preventing client aggregation chaperones often relay substrates within a network while preventing off-pathway chaperones from accessing the substrate. Here we show that a conserved lid motif lining the substrate-binding groove of the Get3 ATPase enables these important?functions during the targeted delivery of tail-anchored membrane proteins (TAs) to the endoplasmic reticulum. The lid prevents promiscuous TA
Wed Jan 02 00:00:00 UTC 2019
MICU1 Interacts with the D-Ring of the MCU Pore to Control Its Ca2+ Flux and Sensitivity to Ru360.
Molecular cell
Paillard M,Csordás G,Huang KT,Várnai P,Joseph SK,Hajnóczky G
Proper control of the mitochondrial Ca uniporter's pore (MCU) is required to allow Ca-dependent activation of oxidative metabolism and to avoid mitochondrial Ca overload and cell death. The MCU's gatekeeping and cooperative activation is mediated by the Ca-sensing MICU1 protein which has been proposed to form dimeric complexes anchored to the EMRE scaffold of MCU. We unexpectedly find that MICU1 suppresses inhibition of MCU by ruthenium red/Ru360 which bind to MCU's DIME motif the selectivi
Thu Nov 15 00:00:00 UTC 2018
UBIAD1 suppresses the proliferation of bladder carcinoma cells by regulating H-Ras intracellular trafficking via interaction with the C-terminal domain of H-Ras.
Cell death & disease
Xu Z,Duan F,Lu H,Abdulkadhim Dragh M,Xia Y,Liang H,Hong L
UbiA prenyltransferase domain-containing protein 1 (UBIAD1) plays a key role in biosynthesis of vitamin K2 and coenzyme Q10 using geranylgeranyl diphosphate (GGPP). However, the mechanism by which UBIAD1 participates in tumorigenesis remains unknown. This study show that UBIAD1 interacts with H-Ras, retains H-Ras in the Golgi apparatus, prevents H-Ras trafficking from the Golgi apparatus to the plasma membrane, blocks the aberrant activation of Ras/MAPK signaling, and inhibits the proliferation
Wed Dec 05 00:00:00 UTC 2018
Phosphorylation of SMC1A promotes hepatocellular carcinoma cell proliferation and migration.
International journal of biological sciences
Zhang Y,Yi F,Wang L,Wang Z,Zhang N,Wang Z,Li Z,Song X,Wei S,Cao L
Structural maintenance of chromosomes protein 1A (SMC1A) has been implicated in the development of a variety of cancer types. However its role in hepatocellular carcinoma remains unknown. In this study we found that phosphorylated SMC1A was highly expressed in HepG2 and Bel7402 cells when compared with other cancer cell lines. Furthermore SMC1A knockdown dramatically reduced HepG2 and Bel7402 cell proliferation and migration. Re-expressing phosphomimetic mutants S957DS966D significantly enhanced
Mon Aug 12 00:00:00 UTC 2019
Defining the Role of Estrogen Receptor β in the Regulation of Female Fertility.
Endocrinology
Rumi MAK,Singh P,Roby KF,Zhao X,Iqbal K,Ratri A,Lei T,Cui W,Borosha S,Dhakal P,Kubota K,Chakraborty D,Vivian JL,Wolfe MW,Soares MJ
Estrogens are essential hormones for the regulation of fertility. Cellular responses to estrogens are mediated by estrogen receptor α (ESR1) and estrogen receptor β (ESR2). In mouse and rat models, disruption of Esr1 causes infertility in both males and females. However, the role of ESR2 in reproductive function remains undecided because of a wide variation in phenotypic observations among Esr2-mutant mouse strains. Regulatory pathways independent of ESR2 binding to its cognate DNA re
Sat Jul 01 00:00:00 UTC 2017
Itm2a silencing rescues lamin A mediated inhibition of 3T3-L1 adipocyte differentiation.
Adipocyte
Davies SJ,Ryan J,O'Connor PBF,Kenny E,Morris D,Baranov PV,O'Connor R,McCarthy TV
Dysregulation of adipose tissue metabolism is associated with multiple metabolic disorders. One such disease known as Dunnigan-type familial partial lipodystrophy (FPLD2) is characterized by defective fat metabolism and storage. FPLD2 is caused by a specific subset of mutations in the LMNA gene. The mechanisms by which LMNA mutations lead to the adipose specific FPLD2 phenotype have yet to be determined in detail. We used RNA-Seq analysis to assess the effects of wild-type (WT) and mutant (R482W
Mon Oct 02 00:00:00 UTC 2017
NEK7 is an essential mediator of NLRP3 activation downstream of potassium efflux.
Nature
He Y,Zeng MY,Yang D,Motro B,Núñez G
Inflammasomes are intracellular protein complexes that drive the activation of inflammatory caspases. So far, four inflammasomes involving NLRP1, NLRP3, NLRC4 and AIM2 have been described that recruit the common adaptor protein ASC to activate caspase-1, leading to the secretion of mature IL-1β and IL-18 proteins. The NLRP3 inflammasome has been implicated in the pathogenesis of several acquired inflammatory diseases as well as cryopyrin-associated periodic fever syndromes (CAPS) caused by
Thu Feb 18 00:00:00 UTC 2016
The E3 ubiquitin protein ligase MDM2 dictates all-trans retinoic acid-induced osteoblastic differentiation of osteosarcoma cells by modulating the degradation of RARα.
Oncogene
Ying M,Zhang L,Zhou Q,Shao X,Cao J,Zhang N,Li W,Zhu H,Yang B,He Q
Retinoic acid receptor alpha (RARα) has a critical role in the differentiation process of osteosarcoma cells induced by all-trans retinoic acid (ATRA). However degradation of RARα through ubiquitin proteasome pathway weakens the differentiation efficiency of osteosarcoma cells. In this study we discover that murine double minute-2 (MDM2) acts as an E3 ubiquitin ligase to target RARα for degradation. We observe that MDM2 is required for RARα polyubiquitination and proteaso
Thu Aug 18 00:00:00 UTC 2016
A G Protein-biased Designer G Protein-coupled Receptor Useful for Studying the Physiological Relevance of Gq/11-dependent Signaling Pathways.
The Journal of biological chemistry
Hu J,Stern M,Gimenez LE,Wanka L,Zhu L,Rossi M,Meister J,Inoue A,Beck-Sickinger AG,Gurevich VV,Wess J
Designerreceptorsexclusivelyactivated by adesignerdrug (DREADDs) are clozapine-N-oxide-sensitive designer G protein-coupled receptors (GPCRs) that have emerged as powerful novel chemogenetic tools to study the physiological relevance of GPCR signaling pathways in specific cell types or tissues. Like endogenous GPCRs clozapine-N-oxide-activated DREADDs do not only activate heterotrimeric G proteins but can also trigger β-arrestin-dependent (G protein-independent) signaling. To dissect the re
Fri Apr 08 00:00:00 UTC 2016
Reciprocal signals between microglia and neurons regulate α-synuclein secretion by exophagy through a neuronal cJUN-N-terminal kinase-signaling axis.
Journal of neuroinflammation
Christensen DP,Ejlerskov P,Rasmussen I,Vilhardt F
BACKGROUND:Secretion of proteopathic α-synuclein (α-SNC) species from neurons is a suspected driving force in the propagation of Parkinson's disease (PD). We have previously implicated exophagy, the exocytosis of autophagosomes, as a dominant mechanism of α-SNC secretion in differentiated PC12 or SH-SY5Y nerve cells. Here we have examined the regulation of exophagy associated with different forms of nerve cell stress relevant to PD. RESULTS:We identify cJUN-N-terminal kinase (J
Tue Mar 08 00:00:00 UTC 2016
Rapid genome assembly and comparison decode intrastrain variation in human alphaherpesviruses.
mBio
Parsons LR,Tafuri YR,Shreve JT,Bowen CD,Shipley MM,Enquist LW,Szpara ML
Herpes simplex virus (HSV) is a widespread pathogen that causes epithelial lesions with recurrent disease that manifests over a lifetime. The lifelong aspect of infection results from latent viral infection of neurons, a reservoir from which the virus reactivates periodically. Recent work has demonstrated the breadth of genetic variation in globally distributed HSV strains. However, the amount of variation or capacity for mutation within one strain has not been well studied. Here we developed an
Tue Mar 31 00:00:00 UTC 2015
hnRNP K coordinates transcriptional silencing by SETDB1 in embryonic stem cells.
PLoS genetics
Thompson PJ,Dulberg V,Moon KM,Foster LJ,Chen C,Karimi MM,Lorincz MC
Retrotransposition of endogenous retroviruses (ERVs) poses a substantial threat to genome stability. Transcriptional silencing of a subset of these parasitic elements in early mouse embryonic and germ cell development is dependent upon the lysine methyltransferase SETDB1, which deposits H3K9 trimethylation (H3K9me3) and the co-repressor KAP1, which binds SETDB1 when SUMOylated. Here we identified the transcription co-factor hnRNP K as a novel binding partner of the SETDB1/KAP1 complex in mouse e
Thu Jan 01 00:00:00 UTC 2015
