ONC201 kills solid tumor cells by triggering an integrated stress response dependent on ATF4 activation by specific eIF2α kinases.

abstract：:Interleukin-2 (IL-2)-inducible T cell kinase (ITK) mediates T cell receptor (TCR) signaling primarily to stimulate the production of cytokines, such as IL-4, IL-5, and IL-13, from T helper 2 (TH2) cells. Compared to wild-type mice, ITK knockout mice are resistant to asthma and exhibit reduced lung inflammation and dec...

journal_title：Science signaling

authors： Sun Y,Peng I,Webster JD,Suto E,Lesch J,Wu X,Senger K,Francis G,Barrett K,Collier JL,Burch JD,Zhou M,Chen Y,Chan C,Eastham-Anderson J,Ngu H,Li O,Staton T,Havnar C,Jaochico A,Jackman J,Jeet S,Riol-Blanco L,Wu

更新日期：2015-12-01 00:00:00

abstract：:The prevalence, presentation, and progression of Alzheimer's disease (AD) differ between men and women, although β-amyloid (Aβ) deposition is a pathological hallmark of AD in both sexes. Aβ-induced activation of the neuronal glutamate receptor mGluR5 is linked to AD progression. However, we found that mGluR5 exhibits ...

journal_title：Science signaling

authors： Abd-Elrahman KS,Albaker A,de Souza JM,Ribeiro FM,Schlossmacher MG,Tiberi M,Hamilton A,Ferguson SSG

更新日期：2020-12-15 00:00:00

abstract：:T helper (T(H)) cells integrate biochemical cues present in the tissue microenvironment and produce cytokines that orchestrate immune responses. Previous discoveries have revealed a qualitative understanding of how T(H) cells process this biochemical information; however, the lack of methods to quantify how well these...

journal_title：Science signaling

authors： Klinke DJ 2nd,Cheng N,Chambers E

更新日期：2012-04-17 00:00:00

abstract：:Spontaneous neural differentiation of embryonic stem cells is induced by Noggin-mediated inhibition of bone morphogenetic protein 4 (BMP4) signaling. RhoA is a guanosine triphosphatase (GTPase) that regulates cytoskeletal dynamics and gene expression, both of which control stem cell fate. We found that disruption of S...

journal_title：Science signaling

authors： Yang J,Wu C,Stefanescu I,Jakobsson L,Chervoneva I,Horowitz A

更新日期：2016-07-26 00:00:00

abstract：:A central component of receptor-evoked Ca(2+) signaling is store-operated Ca(2+) entry (SOCE), which is activated by the assembly of STIM1-Orai1 channels in endoplasmic reticulum (ER) and plasma membrane (PM) (ER-PM) junctions in response to depletion of ER Ca(2+). We report that STIM2 enhances agonist-mediated activa...

journal_title：Science signaling

authors： Ong HL,de Souza LB,Zheng C,Cheng KT,Liu X,Goldsmith CM,Feske S,Ambudkar IS

更新日期：2015-01-13 00:00:00

abstract：:Prokaryotic cell wall biosynthesis is coordinated with cell growth and division, but the mechanisms regulating this dynamic process remain obscure. Here, we describe a phosphorylation-dependent regulatory complex that controls peptidoglycan (PG) biosynthesis in Mycobacterium tuberculosis. We found that PknB, a PG-resp...

journal_title：Science signaling

authors： Gee CL,Papavinasasundaram KG,Blair SR,Baer CE,Falick AM,King DS,Griffin JE,Venghatakrishnan H,Zukauskas A,Wei JR,Dhiman RK,Crick DC,Rubin EJ,Sassetti CM,Alber T

更新日期：2012-01-24 00:00:00

abstract：:Intracranial aneurysms are common but are generally untreated, and their rupture can lead to subarachnoid hemorrhage. Because of the poor prognosis associated with subarachnoid hemorrhage, preventing the progression of intracranial aneurysms is critically important. Intracranial aneurysms are caused by chronic inflamm...

journal_title：Science signaling

authors： Aoki T,Frȍsen J,Fukuda M,Bando K,Shioi G,Tsuji K,Ollikainen E,Nozaki K,Laakkonen J,Narumiya S

更新日期：2017-02-07 00:00:00

abstract：:The oral bacterium Fusobacterium nucleatum is often found in colorectal cancer (CRC). In the 21 July 2020 issue of Science Signaling, Casasanta et al show that CRC cell-resident F. nucleatum promotes cytokine secretion that may potentiate tumor growth and metastatic progression in patients. ...

journal_title：Science signaling

authors： Meyerson M

更新日期：2020-08-11 00:00:00

abstract：:Inositol pyrophosphates are highly energetic inositol polyphosphate molecules present in organisms from slime molds and yeast to mammals. Distinct classes of enzymes generate different forms of inositol pyrophosphates. The biosynthesis of these substances principally involves phosphorylation of inositol hexakisphospha...

journal_title：Science signaling

authors： Chakraborty A,Kim S,Snyder SH

更新日期：2011-08-23 00:00:00

abstract：:Transitional B cells must actively undergo selection for self-tolerance before maturing into their resting follicular B cell successors. We found that metabolic quiescence was acquired at the follicular B cell stage in both humans and mice. In follicular B cells, the expression of genes involved in ribosome biogenesis...

journal_title：Science signaling

authors： Farmer JR,Allard-Chamard H,Sun N,Ahmad M,Bertocchi A,Mahajan VS,Aicher T,Arnold J,Benson MD,Morningstar J,Barmettler S,Yuen G,Murphy SJH,Walter JE,Ghebremichael M,Shalek AK,Batista F,Gerszten R,Pillai S

更新日期：2019-10-22 00:00:00

abstract：:The protein kinase ATM is a master regulator of the DNA damage response but also responds directly to oxidative stress. Loss of ATM causes ataxia telangiectasia, a neurodegenerative disorder with pleiotropic symptoms that include cerebellar dysfunction, cancer, diabetes, and premature aging. We genetically separated t...

journal_title：Science signaling

authors： Lee JH,Mand MR,Kao CH,Zhou Y,Ryu SW,Richards AL,Coon JJ,Paull TT

更新日期：2018-01-09 00:00:00

abstract：:Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is an endogenous secreted peptide and, in preclinical studies, preferentially induces apoptosis in tumor cells rather than in normal cells. The acquisition of resistance in cells exposed to TRAIL or its mimics limits their clinical efficacy. Because kinas...

journal_title：Science signaling

authors： So J,Pasculescu A,Dai AY,Williton K,James A,Nguyen V,Creixell P,Schoof EM,Sinclair J,Barrios-Rodiles M,Gu J,Krizus A,Williams R,Olhovsky M,Dennis JW,Wrana JL,Linding R,Jorgensen C,Pawson T,Colwill K

更新日期：2015-04-07 00:00:00

abstract：:Jiang et al. (Research Article, 11 October 2011, DOI: 10.1126/scisignal.2002152) used a combined experimental and computational modeling approach to study the dynamic response behavior of covalent modification cycles in the presence of downstream targets ("loads"). Despite remarkable agreement between experiments and ...

journal_title：Science signaling

authors： Straube R

更新日期：2012-01-03 00:00:00

abstract：:Store-operated Ca2+ entry (SOCE) channels are highly selective Ca2+ channels activated by the endoplasmic reticulum (ER) sensors STIM1 and STIM2. Their direct interaction with the pore-forming plasma membrane ORAI proteins (ORAI1, ORAI2, and ORAI3) leads to sustained Ca2+ fluxes that are critical for many cellular fun...

journal_title：Science signaling

authors： Eckstein M,Vaeth M,Aulestia FJ,Costiniti V,Kassam SN,Bromage TG,Pedersen P,Issekutz T,Idaghdour Y,Moursi AM,Feske S,Lacruz RS

更新日期：2019-04-23 00:00:00

abstract：:The fluorescent properties of the amino acid tryptophan make it a useful tool for fluorometric assays. Because tryptophan fluorescence is remarkably sensitive to the polarity of the environment, it can be used to determine the affinity of tryptophan-containing peptides for phospholipid vesicles of varying compositions...

journal_title：Science signaling

authors： Kraft CA,Garrido JL,Leiva-Vega L,Romero G

更新日期：2009-12-01 00:00:00

abstract：:MicroRNAs (miRNAs) are small noncoding RNAs that suppress the abundance of partially complementary mRNAs and inhibit their translation. Each miRNA can regulate hundreds of mRNAs, sometimes strongly but often weakly, to mediate a diverse array of biological functions, including proliferation, cell signaling, differenti...

journal_title：Science signaling

authors： Hata A,Lieberman J

更新日期：2015-03-17 00:00:00

abstract：:TRPM2 is a Ca2+-permeable cation channel that is specifically activated by adenosine diphosphoribose (ADPR). Channel activation in the plasma membrane leads to Ca2+ influx and has been linked to apoptotic mechanisms. The primary agonist, ADPR, is produced both extra- and intracellularly and causes increases in intrace...

journal_title：Science signaling

authors： Lange I,Yamamoto S,Partida-Sanchez S,Mori Y,Fleig A,Penner R

更新日期：2009-05-19 00:00:00

abstract：:The C-terminal guanine nucleotide exchange factor (GEF) module of Trio (TrioC) transfers signals from the Gαq/11 subfamily of heterotrimeric G proteins to the small guanosine triphosphatase (GTPase) RhoA, enabling Gαq/11-coupled G protein-coupled receptors (GPCRs) to control downstream events, such as cell motility an...

journal_title：Science signaling

authors： Bandekar SJ,Arang N,Tully ES,Tang BA,Barton BL,Li S,Gutkind JS,Tesmer JJG

更新日期：2019-02-19 00:00:00

abstract：:The scattering of cultured epithelial cells in response to hepatocyte growth factor (HGF) is a model system that recapitulates key features of metastatic cell behavior in vitro, including disruption of cell-cell adhesions and induction of cell migration. We have developed image analysis tools that do not require fluor...

journal_title：Science signaling

authors： Loerke D,le Duc Q,Blonk I,Kerstens A,Spanjaard E,Machacek M,Danuser G,de Rooij J

更新日期：2012-07-03 00:00:00

abstract：:Exosomes are paracrine regulators of the tumor microenvironment and contain complex cargo. We previously reported that exosomes released from acute myeloid leukemia (AML) cells can suppress residual hematopoietic stem and progenitor cell (HSPC) function indirectly through stromal reprogramming of niche retention facto...

journal_title：Science signaling

authors： Hornick NI,Doron B,Abdelhamed S,Huan J,Harrington CA,Shen R,Cambronne XA,Chakkaramakkil Verghese S,Kurre P

更新日期：2016-09-06 00:00:00

abstract：:Toll-like receptors (TLRs) recognize pathogen-associated molecular patterns (PAMPs) and stimulate the innate immune response through the production of cytokines. The innate immune response depends on the timing of encountering PAMPs, suggesting a short-term "memory." In particular, activation of TLR3 appears to prime ...

journal_title：Science signaling

authors： Liu B,Liu Q,Yang L,Palaniappan SK,Bahar I,Thiagarajan PS,Ding JL

更新日期：2016-07-12 00:00:00

abstract：:The prevailing view has been that N-terminally truncated p53 family isoforms (ΔNp53, ΔNp63, and DNp73) predominantly counteract cell cycle arrest and apoptosis. Recent progress in the field extend these well-known functions and place these isoforms in the center of a comprehensive regulatory network controlling major ...

journal_title：Science signaling

authors： Engelmann D,Pützer BM

更新日期：2014-09-30 00:00:00

abstract：:Cytosolic pattern recognition receptors (PRRs) sense intracellular nucleic acids from pathogens such as bacteria and viruses, which leads to the induction of type I interferon (IFN) responses that are essential for an effective immune response. Further, these PRR pathways can be aberrantly activated by self DNA, which...

journal_title：Science signaling

authors： Bowie A

更新日期：2012-03-06 00:00:00

abstract：:Given its fundamental role in development and cancer, the Wnt-β-catenin signaling pathway is tightly controlled at multiple levels. RING finger protein 43 (RNF43) is an E3 ubiquitin ligase originally found in stem cells and proposed to inhibit Wnt signaling by interacting with the Wnt receptors of the Frizzled family....

journal_title：Science signaling

authors： Loregger A,Grandl M,Mejías-Luque R,Allgäuer M,Degenhart K,Haselmann V,Oikonomou C,Hatzis P,Janssen KP,Nitsche U,Gradl D,van den Broek O,Destree O,Ulm K,Neumaier M,Kalali B,Jung A,Varela I,Schmid RM,Rad R,Busch DH

更新日期：2015-09-08 00:00:00

abstract：:In a mouse model of Parkinson's disease, new evidence shows that l-DOPA, which is used to treat the symptoms of the disease but also causes dyskinesia, results in a persistent activation of the protein kinase mTOR (mammalian target of rapamycin) in a subset of striatal medium spiny neurons. Moreover, blockade of a spe...

journal_title：Science signaling

authors： Klann E

更新日期：2009-07-21 00:00:00

abstract：:Huntington's disease (HD) is a neurodegenerative disease caused by an expansion in the huntingtin protein (also called Htt) that induces neuronal cell death with age. We found that the treatment of 12-month-old symptomatic heterozygous and homozygous zQ175 huntingtin knockin mice for 12 weeks with CTEP, a negative all...

journal_title：Science signaling

authors： Abd-Elrahman KS,Hamilton A,Hutchinson SR,Liu F,Russell RC,Ferguson SSG

更新日期：2017-12-19 00:00:00

abstract：:We previously developed a web tool, Transcriptomine, to explore expression profiling data sets involving small-molecule or genetic manipulations of nuclear receptor signaling pathways. We describe advances in biocuration, query interface design, and data visualization that enhance the discovery of uncharacterized biol...

journal_title：Science signaling

authors： Becnel LB,Ochsner SA,Darlington YF,McOwiti A,Kankanamge WH,Dehart M,Naumov A,McKenna NJ

更新日期：2017-04-25 00:00:00

abstract：:Chemokines were initially thought of only as regulators of the migration of developing thymocytes between different compartments of the thymus and were predicted also to be involved in early stages of thymocyte development. Recent data have suggested additional functions for the chemokine receptor CXCR4-a G protein-co...

journal_title：Science signaling

authors： Ahamed JA,Madhivadhani P

更新日期：2010-04-27 00:00:00

abstract：:Premature labor and consequent neonatal mortality may be prevented by stimulating the expression of PIBF1 in uterine B cells. ...

journal_title：Science signaling

authors： Ferrarelli LK

更新日期：2017-01-17 00:00:00

abstract：:The differentiation of fibroblasts into a transient population of highly activated, extracellular matrix (ECM)-producing myofibroblasts at sites of tissue injury is critical for normal tissue repair. Excessive myofibroblast accumulation and persistence, often as a result of a failure to undergo apoptosis when tissue r...

journal_title：Science signaling

authors： Selvarajah B,Azuelos I,Platé M,Guillotin D,Forty EJ,Contento G,Woodcock HV,Redding M,Taylor A,Brunori G,Durrenberger PF,Ronzoni R,Blanchard AD,Mercer PF,Anastasiou D,Chambers RC

更新日期：2019-05-21 00:00:00