Abstract：
:MicroRNAs (miRs) are a class of single-stranded, non-coding RNAs of about 22 nucleotides in length. Increasing evidence implicates miRs in myocardial disease processes. Here we show that miR-199b is a direct calcineurin/NFAT target gene that increases in expression in mouse and human heart failure, and targets the nuclear NFAT kinase dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1a (Dyrk1a), constituting a pathogenic feed forward mechanism that affects calcineurin-responsive gene expression. Mutant mice overexpressing miR-199b, or haploinsufficient for Dyrk1a, are sensitized to calcineurin/NFAT signalling or pressure overload and show stress-induced cardiomegaly through reduced Dyrk1a expression. In vivo inhibition of miR-199b by a specific antagomir normalized Dyrk1a expression, reduced nuclear NFAT activity and caused marked inhibition and even reversal of hypertrophy and fibrosis in mouse models of heart failure. Our results reveal that microRNAs affect cardiac cellular signalling and gene expression, and implicate miR-199b as a therapeutic target in heart failure.
journal_name
Nat Cell Bioljournal_title
Nature cell biologyauthors
da Costa Martins PA,Salic K,Gladka MM,Armand AS,Leptidis S,el Azzouzi H,Hansen A,Coenen-de Roo CJ,Bierhuizen MF,van der Nagel R,van Kuik J,de Weger R,de Bruin A,Condorelli G,Arbones ML,Eschenhagen T,De Windt LJdoi
10.1038/ncb2126subject
Has Abstractpub_date
2010-12-01 00:00:00pages
1220-7issue
12eissn
1465-7392issn
1476-4679pii
ncb2126journal_volume
12pub_type
杂志文章abstract：:To control cell proliferation, signal transduction needs to regulate the cell-cycle machinery. Recent findings show that Akt - a major kinase that coordinates diverse signalling pathways - phosphorylates Skp2, a subunit of the SCF-Skp2 ubiquitin ligase that targets key cell-cycle regulators. Akt1-dependent phosphoryla...
journal_title：Nature cell biology
pub_type： 评论,新闻
doi：10.1038/ncb0409-377
更新日期：2009-04-01 00:00:00
abstract：:In plants, cell shape is defined by the cell wall, and changes in cell shape and size are dictated by modification of existing cell walls and deposition of newly synthesized cell-wall material. In root hairs, expansion occurs by a process called tip growth, which is shared by root hairs, pollen tubes and fungal hyphae...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb2294
更新日期：2011-07-17 00:00:00
abstract：:Treatment of cultured vertebrate neurons with nitric oxide leads to growth-cone collapse, axon retraction and the reconfiguration of axonal microtubules. We show that the light chain of microtubule-associated protein (MAP) 1B is a substrate for S-nitrosylation in vivo, in cultured cells and in vitro. S-nitrosylation o...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb1625
更新日期：2007-09-01 00:00:00
abstract：:The formation of branched epithelial networks is fundamental to the development of many organs, such as the lung, the kidney or the vasculature. Little is known about the mechanisms that control cell rearrangements during tubulogenesis and regulate the size of individual tubes. Recent studies indicate that whereas the...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb1049
更新日期：2003-10-01 00:00:00
abstract：:Micronucleation of missegregated chromatin can lead to substantial chromosome rearrangements via chromothripsis. However, the molecular details of micronucleus-based chromothripsis are still unclear. Now, an elegant system that specifically induces missegregation of the Y chromosome provides insight into this process,...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb3458
更新日期：2016-12-23 00:00:00
abstract：:Collective cell migration occurs in a range of contexts: cancer cells frequently invade in cohorts while retaining cell-cell junctions. Here we show that collective invasion by cancer cells depends on decreasing actomyosin contractility at sites of cell-cell contact. When actomyosin is not downregulated at cell-cell c...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb2133
更新日期：2011-01-01 00:00:00
abstract：:During meiosis, homologous chromosomes are sorted into pairs and are then intimately aligned, or synapsed, along their lengths while a proteinaceous structure, the synaptonemal complex, is assembled between them. However, little is known about how chromosomes first recognise each other. Here we show, by comparing the ...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb1168
更新日期：2004-09-01 00:00:00
abstract：:The mitochondrial inner membrane is the central energy-converting membrane of eukaryotic cells. The electrochemical proton gradient generated by the respiratory chain drives the ATP synthase. To maintain this proton-motive force, the inner membrane forms a tight barrier and strictly controls the translocation of ions....
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb1635
更新日期：2007-10-01 00:00:00
abstract：:The initial differential treatment of the two X chromosomes during X-chromosome inactivation is controlled by the X-inactivation centre (Xic). This locus determines how many X chromosomes are present in a cell ('counting') and which X chromosome will be inactivated in female cells ('choice'). Critical control sequence...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb1365
更新日期：2006-03-01 00:00:00
abstract：:Cell division is fundamental for all organisms. Here we report a genome-scale RNA-mediated interference screen in HeLa cells designed to identify human genes that are important for cell division. We have used a library of endoribonuclease-prepared short interfering RNAs for gene silencing and have used DNA content ana...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb1659
更新日期：2007-12-01 00:00:00
abstract：:Here we show that human Zeste White 10 (Zw10) and Rough deal (Rod) are new components of the mitotic checkpoint, as cells lacking these proteins at kinetochores fail to arrest in mitosis when exposed to microtubule inhibitors. Checkpoint failure and premature mitotic exit may explain why cells defective for hZw10 and ...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/35046598
更新日期：2000-12-01 00:00:00
abstract：:Despite the presence of mutations in APC or beta-catenin, which are believed to activate the Wnt signalling cascade constitutively, most colorectal cancers show cellular heterogeneity when beta-catenin localization is analysed, indicating a more complex regulation of Wnt signalling. We explored this heterogeneity with...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb2048
更新日期：2010-05-01 00:00:00
abstract：:Sensing and clearance of dysfunctional lysosomes is critical for cellular homeostasis. Here we show that transcription factor EB (TFEB)-a master transcriptional regulator of lysosomal biogenesis and autophagy-is activated during the lysosomal damage response, and its activation is dependent on the function of the ATG ...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/s41556-020-00583-9
更新日期：2020-10-01 00:00:00
abstract：:Guard cells, which form stomata in leaf epidermes, sense a multitude of environmental signals and integrate this information to regulate stomatal movements. Compared with the advanced understanding of light and water stress responses in guard cells, the molecular mechanisms that underlie stomatal CO(2) signalling have...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb1387
更新日期：2006-04-01 00:00:00
abstract：:The tumour vascular microenvironment supports tumorigenesis not only by supplying oxygen and diffusible nutrients but also by secreting soluble factors that promote tumorigenesis. Here we identify a feedforward mechanism in which endothelial cells (ECs), in response to tumour-derived mediators, release angiocrines dri...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb2954
更新日期：2014-05-01 00:00:00
abstract：:Cells of multicellular organisms need to adopt specific morphologies. However, the molecular mechanisms bringing about membrane topology changes are far from understood-mainly because knowledge of membrane-shaping proteins that can promote local membrane curvatures is still limited. Our analyses unveiled that several ...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/s41556-019-0381-7
更新日期：2019-10-01 00:00:00
abstract：:The Notch1 gene has an important role in mammalian cell-fate decision and tumorigenesis. Upstream control mechanisms for transcription of this gene are still poorly understood. In a chemical genetics screen for small molecule activators of Notch signalling, we identified epidermal growth factor receptor (EGFR) as a ke...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb1750
更新日期：2008-08-01 00:00:00
abstract：:The pericentriolar material (PCM), the microtubule-organizing component of the centrosome, contains a multitude of proteins and is commonly described as an amorphous cloud surrounding the centrioles. However, the days of the PCM as an unstructured matrix are numbered. Using super-resolution microscopy, several reports...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb2617
更新日期：2012-11-01 00:00:00
abstract：:Mitochondrial function degenerates with ageing and in ageing-related neuromuscular degenerative diseases, causing physiological decline of the cell. Factors that can delay the degenerative process are actively sought after. Here, we show that reduced cytosolic protein synthesis is a robust cellular strategy that suppr...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb1769
更新日期：2008-09-01 00:00:00
abstract：:For accurate segregation of chromosomes during cell division, microtubule fibres must attach sister kinetochores to opposite poles of the mitotic spindle (bi-orientation). Aurora kinases are linked to oncogenesis and have been implicated in the regulation of chromosome-microtubule attachments. Although loss of Aurora ...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb1102
更新日期：2004-03-01 00:00:00
abstract：:MicroRNAs (miRNAs) have emerged as novel cancer genes. In particular, the miR-17-92 cluster, containing six individual miRNAs, is highly expressed in haematopoietic cancers and promotes lymphomagenesis in vivo. Clinical use of these findings hinges on isolating the oncogenic activity within the 17-92 cluster and defin...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb2037
更新日期：2010-04-01 00:00:00
abstract：:Compartmentalization has long been known to have a key role in regulation of cellular processes. By keeping enzymes and regulatory complexes in compartments where the delivery of substrate or exit of product is controlled, competing reactions can occur simultaneously in different parts of the cell. Moreover, spatial c...
journal_title：Nature cell biology
pub_type： 杂志文章,评审
doi：10.1038/35014078
更新日期：2000-06-01 00:00:00
abstract：:During cell division, many animal cells transform into a spherical shape and assemble a contractile ring composed of actin filaments and myosin motors at the equator to separate the cell body into two. Although actomyosin regulatory proteins are spatio-temporally controlled during cytokinesis, the direct contribution ...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb3142
更新日期：2015-04-01 00:00:00
abstract：:Integrin-containing focal adhesions transmit extracellular signals across the plasma membrane to modulate cell adhesion, signalling and survival. Although integrins are known to undergo continuous endo/exocytic traffic, the potential impact of endocytic traffic on integrin-induced signals is unknown. Here, we demonstr...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb3250
更新日期：2015-11-01 00:00:00
abstract：:During mammalian development, neuroepithelial cells function as mitotic progenitors, which self-renew and generate neurons. Although spindle orientation is important for such polarized cells to undergo symmetric or asymmetric divisions, its role in mammalian neurogenesis remains unclear. Here we show that control of s...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb1673
更新日期：2008-01-01 00:00:00
abstract：:Obesity occurs when excess energy accumulates in white adipose tissue (WAT), whereas brown adipose tissue (BAT), specialized for energy expenditure through thermogenesis, potently counteracts obesity. Factors that induce brown adipocyte commitment and energy expenditure would be a promising defence against adiposity. ...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb2867
更新日期：2013-12-01 00:00:00
abstract：:Reference datasets should be accessible independently of scientific papers in a citable form, allowing attribution. ...
journal_title：Nature cell biology
pub_type： 社论
doi：10.1038/ncb1109-1273a
更新日期：2009-11-01 00:00:00
abstract：:Primordial germ cell (PGC) development in the human fetus remains relatively uncharted. A new study suggests that epigenetic reprogramming and sex differentiation in human PGCs occur asynchronously over an extended time period. This finding raises questions and implications for in vitro PGC differentiation. ...
journal_title：Nature cell biology
pub_type： 评论,杂志文章
doi：10.1038/ncb2665
更新日期：2013-01-01 00:00:00
abstract：:Cholesterol is a structural component of animal membranes that influences fluidity, permeability and formation of lipid microdomains. It is also a precursor to signalling molecules, including mammalian steroid hormones and insect ecdysones. The nematode Caenorhabditis elegans requires too little cholesterol for it to ...
journal_title：Nature cell biology
pub_type： 杂志文章,评审
doi：10.1038/ncb0803-684
更新日期：2003-08-01 00:00:00
abstract：:Changes in phosphorylation of the carboxy-terminal domain (CTD) of RNA polymerase II (RNAP) are associated with transcription initiation, elongation and termination. Sites of active transcription are generally characterized by hyperphosphorylated RNAP, particularly at Ser 2 residues, whereas inactive or poised genes m...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb1663
更新日期：2007-12-01 00:00:00
