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 were differentially phosphorylated, and systematic depletion of each of these differentially phosphorylated proteins by small interfering RNA (siRNA) identified at least 10 potential regulators of recovery. Astrin, a protein associated with the mitotic spindle, was among the potential regulators of recovery. We found that astrin controlled the abundance of the cell cycle regulator p53 during DNA damage-induced arrest. Cells in which astrin was depleted had decreased murine double minute 2 (MDM2) abundance and increased p53 at the later stages of the DNA damage response. Astrin was required for continued expression of genes encoding proteins that promote cell cycle progression in arrested cells. Thus, by controlling p53 abundance in cells recovering from DNA damage, astrin maintains the cells in a state competent to resume the cell cycle.
journal_name
Sci Signaljournal_title
Science signalingauthors
Halim VA,Alvarez-Fernández M,Xu YJ,Aprelia M,van den Toorn HW,Heck AJ,Mohammed S,Medema RHdoi
10.1126/scisignal.2003664subject
Has Abstractpub_date
2013-04-23 00:00:00pages
rs9issue
272eissn
1945-0877issn
1937-9145pii
6/272/rs9journal_volume
6pub_type
杂志文章abstract::Endothelial cell dysfunction, characterized by a diminished response to endothelial cell-dependent vasodilators, is a hallmark of hypertension. TRPV4 channels play a major role in endothelial-dependent vasodilation, a function mediated by local Ca(2+) influx through clusters of functionally coupled TRPV4 channels rath...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.2005052
更新日期:2014-07-08 00:00:00
abstract::l-Glutamate is the main excitatory neurotransmitter in the brain, with postsynaptic responses to its release predominantly mediated by AMPA-type glutamate receptors (AMPARs). A critical component of synaptic plasticity involves changes in the number of responding postsynaptic receptors, which are dynamically recruited...
journal_title:Science signaling
pub_type: 杂志文章,评审
doi:10.1126/scisignal.aar6889
更新日期:2019-01-01 00:00:00
abstract::Microglia mediate neuroprotection and neuropathogenesis but have not been directly associated with behavior. As gatekeepers of the brain's immune system, microglia protect the brain from pathogens but also contribute to inflammation, which may negatively affect neurons. A recent study demonstrates a role for Hoxb8-exp...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.3147jc8
更新日期:2010-11-09 00:00:00
abstract::The European Molecular Biology Organization (EMBO) meeting Visualizing Immune System Complexity, held in January 2009, covered multiple scales, from imaging single molecules to imaging whole animals. In addition to experimental details, there was an emphasis on modeling both for data analysis and as a predictive tool ...
journal_title:Science signaling
pub_type:
doi:10.1126/scisignal.266mr4
更新日期:2009-04-14 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
pub_type: 杂志文章
doi:10.1126/scisignal.3119jc4
更新日期:2010-04-27 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::MKK4 (mitogen-activated protein kinase kinase 4) is a pivotal upstream activator of c-Jun N-terminal kinase and p38. Here, we report that the abundance of MKK4 increases in senescent human diploid fibroblasts through enhanced translation. We identified four microRNAs (miR-15b, miR-24, miR-25, and miR-141) that target ...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.2000442
更新日期:2009-10-27 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::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::Cytotoxic lymphocytes share the presence of the activating receptor NK receptor group 2, member D (NKG2D) and the signaling-competent adaptor DNAX-activating protein 10 (DAP10), which together play an important role in antitumor immune surveillance. Ligand stimulation induces the internalization of NKG2D-DAP10 complex...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.aab2724
更新日期:2015-10-27 00:00:00
abstract::During T cell activation by antigen-presenting cells (APCs), the diverse spatiotemporal organization of components of T cell signaling pathways modulates the efficiency of activation. Here, we found that loss of the tyrosine kinase interleukin-2 (IL-2)-inducible T cell kinase (Itk) in mice altered the spatiotemporal d...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.2001821
更新日期:2011-10-04 00:00:00
abstract::One reported function of the tumor suppressor p19(Arf) is to stabilize p53, providing a critical checkpoint in the response to oncogenic insults. Acute loss of Pten leads to an increase in the abundance of p19(Arf), p53, and p21 proteins as part of a fail-safe senescence response. Here, we report that loss of p19(Arf)...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.2000053
更新日期:2009-08-18 00:00:00
abstract::Although multiple steroid ligands of the glucocorticoid, mineralocorticoid, and progestin families bind to and regulate the activity of mineralocorticoid receptors (MRs), the responses to these ligands differ across species. To understand how the different domains of MRs contribute to the ligand-induced activation or ...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.aao1520
更新日期:2018-07-03 00:00:00
abstract::Ewing's sarcoma (ES) is a rare and highly malignant cancer that grows in the bones or surrounding tissues mostly affecting adolescents and young adults. A chimeric fusion between the RNA binding protein EWS and the ETS family transcription factor FLI1 (EWS-FLI1), which is generated from a chromosomal translocation, is...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.aam8429
更新日期:2017-10-03 00:00:00
abstract::The cytokine interleukin-22 (IL-22), which is a member of the IL-10 family, is produced exclusively by immune cells and activates signal transducer and activator of transcription 3 (STAT3) in nonimmune cells, such as hepatocytes, keratinocytes, and colonic epithelial cells, to drive various processes central to tissue...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.aad9887
更新日期:2016-09-27 00:00:00
abstract::This week, Science Signaling highlights research that uses computational and cell biology approaches to uncover the molecular mechanisms underlying diseases of the central nervous system. In particular, research featured explores the neuronal response to stress due to excess excitatory stimuli, multiple roles for pres...
journal_title:Science signaling
pub_type: 杂志文章,评审
doi:10.1126/scisignal.2004456
更新日期:2013-07-09 00:00:00
abstract::The hexosamine biosynthetic pathway, whose end product is UDP-N acetylglucosamine (UDP-GlcNAc), lies at the base of cellular glycosylation pathways, including glycosylation of lipids, formation of heparin sulfated proteoglycans, and N- and O-linked glycosylation of proteins. Forward genetic studies in Drosophila have ...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.2002789
更新日期:2012-01-17 00:00:00
abstract::Progression through mitosis depends on a large number of protein complexes that regulate the major structural and physiological changes necessary for faithful chromosome segregation. Most, if not all, of the mitotic processes are regulated by a set of mitotic protein kinases that control protein activity by phosphoryl...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.2001993
更新日期:2011-11-08 00:00:00
abstract::Mutations in AMPA receptor recycling machinery underlie cognitive impairment in an intellectual disorder and in neurodegenerative diseases. ...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.aan5454
更新日期:2017-05-02 00:00:00
abstract::Recent studies have identified adaptations of intracellular signaling pathways and target genes that could contribute or modulate the action of antidepressant drugs, as well as exercise-mediated antidepressant responses. Understanding these adaptations, particularly those changes that are common to diverse antidepress...
journal_title:Science signaling
pub_type: 杂志文章,评审
doi:10.1126/stke.118pe19
更新日期:2008-05-06 00:00:00
abstract::Regulatory factor X (Rfx) homologs regulate the transcription of genes necessary for ciliogenesis in invertebrates and vertebrates. Primary cilia are necessary for Hedgehog signaling and regulation of the activity of the transcriptional regulators known as Gli proteins, which are targets of Hedgehog signaling. Here, w...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.2000602
更新日期:2009-11-03 00:00:00
abstract::Cyclic-di-GMP (c-di-GMP) is a bacterial second messenger that transduces internal and external signals and regulates bacterial motility and biofilm formation. Some organisms encode more than 100 c-di-GMP-modulating enzymes, but only for a few has a signal been defined that modulates their activity. We developed and ap...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.aaa1796
更新日期:2015-06-09 00:00:00
abstract::Degrons are the elements that are used by E3 ubiquitin ligases to target proteins for degradation. Most degrons are short linear motifs embedded within the sequences of modular proteins. As regulatory sites for protein abundance, they are important for many different cellular processes, such as progression through the...
journal_title:Science signaling
pub_type: 杂志文章,评审
doi:10.1126/scisignal.aak9982
更新日期:2017-03-14 00:00:00
abstract::The K+/Cl- cotransporter KCC2 is a molecular switch between excitatory and inhibitory effects of GABAergic inputs into neurons. In a pair of exciting studies, Watanabe et al. and Pisella et al. elucidate the role of KCC2 dephosphorylation in this process and reveal its consequences for neurodevelopment and nervous sys...
journal_title:Science signaling
pub_type: 评论,杂志文章,评审
doi:10.1126/scisignal.aay8960
更新日期:2019-10-15 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
pub_type: 杂志文章
doi:10.1126/scisignal.2002657
更新日期:2012-04-17 00:00:00
abstract::The activation of T cells requires the guanine nucleotide exchange factor VAV1. Using mice in which a tag for affinity purification was attached to endogenous VAV1 molecules, we analyzed by quantitative mass spectrometry the signaling complex that assembles around activated VAV1. Fifty VAV1-binding partners were ident...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.aar3083
更新日期:2018-07-10 00:00:00
abstract::Stress is an important contributor to pathological conditions in humans. Hormonal changes that occur during acute and chronic stress situations can affect glucose homeostasis in both healthy people and in those with diabetes. Several studies have reported a negative effect of acute stress on maintenance of blood gluco...
journal_title:Science signaling
pub_type: 杂志文章,评审
doi:10.1126/scisignal.2003508
更新日期:2012-10-23 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::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
pub_type: 杂志文章,评审
doi:10.1126/scisignal.abc4218
更新日期:2020-08-11 00:00:00
abstract::Postsynaptic organizational protein complexes play central roles both in orchestrating synapse formation and in defining the functional properties of synaptic transmission that together shape the flow of information through neuronal networks. A key component of these organizational protein complexes is the family of s...
journal_title:Science signaling
pub_type: 杂志文章,评审
doi:10.1126/scisignal.abd8379
更新日期:2020-12-22 00:00:00