Abstract:
:MicroRNAs (miRNAs), key posttranscriptional regulators of many biological processes, have been implicated in many diseases, including cancer. In a recent paper, Avraham and colleagues take a systems biology approach to determine whether and how miRNAs are involved in the regulation of oncogenic signaling networks downstream of epidermal growth factor (EGF). The authors showed that EGF stimulation orchestrated the transcription of both miRNAs and transcription factors. An early decrease in the abundance of a subset of miRNAs allowed for the induction of messenger RNAs of immediate early genes. Expression of this group of miRNAs was also decreased in tumors that showed deregulated signaling through the EGF receptor (EGFR) or the related receptor HER2. Their biological properties of redundancy, multiplicity, and rapid responsiveness make these small noncoding RNAs important regulators of cell signaling.
journal_name
Sci Signaljournal_title
Science signalingauthors
Herschkowitz JI,Fu Xdoi
10.1126/scisignal.2002182subject
Has Abstractpub_date
2011-07-26 00:00:00pages
jc5issue
184eissn
1945-0877issn
1937-9145pii
scisignal.2002182journal_volume
4pub_type
评论,杂志文章,评审abstract::Slit proteins act as repulsive axon guidance cues by activating receptors of the Roundabout (Robo) family. During early neurogenesis in Drosophila melanogaster, Slit prevents the growth cones of longitudinal tract neurons from inappropriately crossing the midline, thus restricting these cells to trajectories parallel ...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.aam5841
更新日期:2017-06-20 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
pub_type: 杂志文章
doi:10.1126/scisignal.aaf0791
更新日期:2016-07-26 00:00:00
abstract::A challenge for biomedical research is the development of pharmaceuticals that appropriately target disease mechanisms. Natural products can be a rich source of bioactive chemicals for medicinal applications but can act through unknown mechanisms and can be difficult to produce or obtain. To address these challenges, ...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.2004657
更新日期:2013-10-15 00:00:00
abstract::The accumulation of damaged or excess proteins and organelles is a defining feature of metabolic disease in nearly every tissue. Thus, a central challenge in maintaining metabolic homeostasis is the identification, sequestration, and degradation of these cellular components, including protein aggregates, mitochondria,...
journal_title:Science signaling
pub_type: 杂志文章,评审
doi:10.1126/scisignal.aag2298
更新日期:2017-02-28 00:00:00
abstract::By regulating gene expression, microRNAs (miRNAs) play pivotal roles in physiological and pathological processes. However, the regulation of miRNAs is elusive. miR-192 is a key regulator of renal fibrosis and hypertrophy in diabetic nephropathy. Natarajan et al. showed that the miR-192 gene contains an upstream region...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.2004299
更新日期:2013-06-04 00:00:00
abstract::Multicellular organisms rely on complex, fine-tuned protein networks to respond to environmental changes. We used in vitro evolution to explore the role of domain mutation and expansion in the evolution of network complexity. Using random mutagenesis to facilitate family expansion, we asked how versatile and robust th...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.2000416
更新日期:2009-09-08 00:00:00
abstract::Birth defects of the heart and face are common, and most have no known genetic cause, suggesting a role for environmental factors. Maternal fever during the first trimester is an environmental risk factor linked to these defects. Neural crest cells are precursor populations essential to the development of both at-risk...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.aal4055
更新日期:2017-10-10 00:00:00
abstract::How cells recover from a DNA damage-induced arrest is currently poorly understood. We performed large-scale quantitative phosphoproteomics to identify changes in protein phosphorylation that occurred during recovery from arrest in the G2 phase of the cell cycle caused by DNA damage. We identified 154 proteins that wer...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.2003664
更新日期:2013-04-23 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
pub_type: 杂志文章
doi:10.1126/scisignal.aac6757
更新日期:2015-09-08 00:00:00
abstract::Calcium/calmodulin-dependent protein kinase II (CaMKII) plays a central role in Ca2+ signaling throughout the body. In the hippocampus, CaMKII is required for learning and memory. Vertebrate genomes encode four CaMKII homologs: CaMKIIα, CaMKIIβ, CaMKIIγ, and CaMKIIδ. All CaMKIIs consist of a kinase domain, a regulator...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.aaz0240
更新日期:2020-07-21 00:00:00
abstract::Mineralocorticoid receptor (MR) antagonists are effective at treating heart failure. In this issue of Science Signaling, Oakley et al. provide new insight into their cardioprotective actions and highlight the importance of the opposing relationship between the MR and the related glucocorticoid receptor (GR) in the res...
journal_title:Science signaling
pub_type: 杂志文章,评审
doi:10.1126/scisignal.aaw8715
更新日期:2019-04-16 00:00:00
abstract::Mechanical loading of the skeleton is essential for the development, growth, and maintenance of strong, weight-bearing bones. Bone strength is plastic and can be modulated in adults, as illustrated by the increased bone mass in the playing arms of athletes as compared with their nonplaying arms. Our studies have shown...
journal_title:Science signaling
pub_type:
doi:10.1126/scisignal.268pt3
更新日期:2009-04-28 00:00:00
abstract::Deoxyhypusine synthase (DHPS) uses the polyamine spermidine to catalyze the hypusine modification of the mRNA translation factor eIF5A and promotes oncogenesis through poorly defined mechanisms. Because germline deletion of Dhps is embryonically lethal, its role in normal postnatal cellular function in vivo remains un...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.aax0715
更新日期:2019-12-03 00:00:00
abstract::For the first 30 years since its discovery, reversible protein acetylation has been studied and understood almost exclusively in the context of histone modification and gene transcription. With the discovery of non-histone acetylated proteins and acetylation-modifying enzymes in cellular compartments outside the nucle...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.297pe76
更新日期:2009-11-17 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
pub_type: 杂志文章,评审
doi:10.1126/scisignal.2005699
更新日期:2014-09-30 00:00:00
abstract::GIV (Gα-interacting vesicle-associated protein; also known as Girdin) enhances Akt activation downstream of multiple growth factor- and G protein (heterotrimeric guanosine 5'-triphosphate-binding protein)-coupled receptors to trigger cell migration and cancer invasion. We demonstrate that GIV is a tyrosine phosphoprot...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.2002049
更新日期:2011-09-27 00:00:00
abstract::The role of mucin 1 (MUC1) in protecting epithelia from microbial infection, enzymatic digestion, and other irritants has been appreciated for some time. In addition, MUC1 serves as a barrier to embryo implantation. MUC1 is highly abundant in many tumors in which its role in barrier function may serve to protect cells...
journal_title:Science signaling
pub_type: 杂志文章,评审
doi:10.1126/scisignal.127pe35
更新日期:2008-07-08 00:00:00
abstract::Skeletal muscle mass is regulated by activity, metabolism, and the availability of nutrients. During muscle atrophy, MNK2 expression increases. We found that MNK2 (mitogen-activated protein kinase-interacting kinase 2), but not MNK1, inhibited proteins involved in promoting protein synthesis, including eukaryotic tran...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.2002466
更新日期:2012-02-14 00:00:00
abstract::The vascular endothelial growth factor (VEGF) signaling pathway plays a pivotal role in normal development and also represents a major therapeutic target for tumors and intraocular neovascular disorders. The VEGF receptor tyrosine kinases promote angiogenesis by phosphorylating downstream proteins in endothelial cells...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.2003572
更新日期:2013-04-16 00:00:00
abstract::Overuse of β2-adrenoceptor agonist bronchodilators evokes receptor desensitization, decreased efficacy, and an increased risk of death in asthma patients. Bronchodilators that do not target β2-adrenoceptors represent a critical unmet need for asthma management. Here, we characterize the utility of osthole, a coumarin ...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.aax0273
更新日期:2020-11-24 00:00:00
abstract::Biophysical methods and x-ray crystallography have revealed that class A G protein-coupled receptors (GPCRs) can form homodimers. We combined computational approaches with receptor cross-linking, energy transfer, and a newly developed functional export assay to characterize the residues involved in the dimerization in...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.aal2869
更新日期:2018-05-08 00:00:00
abstract::Neutrophil extracellular trap (NET) formation can generate short-term, functional anucleate cytoplasts and trigger loss of cell viability. We demonstrated that the necroptotic cell death effector mixed lineage kinase domain-like (MLKL) translocated from the cytoplasm to the plasma membrane and stimulated downstream NA...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.aao1716
更新日期:2018-09-04 00:00:00
abstract::Interleukin-10 (IL-10) is an important anti-inflammatory cytokine that is produced primarily by macrophages. We investigated mechanisms by which the timing of IL-10 production was controlled in macrophages and found that cyclin-dependent kinase 5 (CDK5) activity was markedly increased in lipopolysaccharide (LPS)-stimu...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.aab3156
更新日期:2015-11-24 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
pub_type: 杂志文章,评审
doi:10.1126/scisignal.2001958
更新日期:2011-08-23 00:00:00
abstract::Antigen-mediated stimulation of the T cell receptor (TCR) triggers activation of nuclear factor κB (NF-κB), a key transcriptional regulator of T cell proliferation and effector cell differentiation. TCR signaling to NF-κB requires both the Carma1-Bcl10-Malt1 (CBM) complex and the inhibitor of κB (IκB) kinase (IKK) com...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.2004882
更新日期:2014-05-13 00:00:00
abstract::Bone morphogenetic proteins (BMPs) and Wnts are growth factors that provide essential patterning signals for cell proliferation and differentiation. Here, we describe a molecular mechanism by which the phosphorylation state of the Drosophila transcription factor Mad determines its ability to transduce either BMP or Wi...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.2002034
更新日期:2011-10-11 00:00:00
abstract::The proteasome plays a pivotal role in the cellular response to oxidative stress. Here, we used biochemical and mass spectrometric methods to investigate structural changes in the 26S proteasomes from yeast and mammalian cells exposed to hydrogen peroxide (H₂O₂). Oxidative stress induced the dissociation of the 20S co...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.2001232
更新日期:2010-12-07 00:00:00
abstract::Epigenetic modifications, such as DNA cytosine methylation, contribute to the mechanisms underlying learning and memory by coordinating adaptive gene expression and neuronal plasticity. Transcription-dependent plasticity regulated by DNA methylation includes synaptic plasticity and homeostatic synaptic scaling. Memory...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.aaf5642
更新日期:2016-08-23 00:00:00
abstract::Frizzleds (FZDs) are a group of seven transmembrane-spanning (7TM) receptors that belong to class F of the G protein-coupled receptor (GPCR) superfamily. FZDs bind WNT proteins to stimulate diverse signaling cascades involved in embryonic development, stem cell regulation, and adult tissue homeostasis. Frizzled 5 (FZD...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.aar5536
更新日期:2018-12-04 00:00:00
abstract::The mechanisms of context-specific differences in signal transduction, such as those that occur among different cell types, are not fully understood. One possibility is that differences in the abundance of proteins change signaling outputs because these proteins compete for binding to hub proteins at critical network ...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.2004560
更新日期:2013-12-17 00:00:00