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 defining its relevant target genes. Here we show that miR-19 is sufficient to promote leukaemogenesis in Notch1-induced T-cell acute lymphoblastic leukaemia (T-ALL) in vivo. In concord with the pathogenic importance of this interaction in T-ALL, we report a novel translocation that targets the 17-92 cluster and coincides with a second rearrangement that activates Notch1. To identify the miR-19 targets responsible for its oncogenic action, we conducted a large-scale short hairpin RNA screen for genes whose knockdown can phenocopy miR-19. Strikingly, the results of this screen were enriched for miR-19 target genes, and include Bim (Bcl2L11), AMP-activated kinase (Prkaa1) and the phosphatases Pten and PP2A (Ppp2r5e). Hence, an unbiased, functional genomics approach reveals a coordinate clampdown on several regulators of phosphatidylinositol-3-OH kinase-related survival signals by the leukaemogenic miR-19.
journal_name
Nat Cell Bioljournal_title
Nature cell biologyauthors
Mavrakis KJ,Wolfe AL,Oricchio E,Palomero T,de Keersmaecker K,McJunkin K,Zuber J,James T,Khan AA,Leslie CS,Parker JS,Paddison PJ,Tam W,Ferrando A,Wendel HGdoi
10.1038/ncb2037subject
Has Abstractpub_date
2010-04-01 00:00:00pages
372-9issue
4eissn
1465-7392issn
1476-4679pii
ncb2037journal_volume
12pub_type
杂志文章abstract::Many classical biologists working in Antarctica have 'gone molecular' to study the physiological basis for life on or below the ice. Investigating the remarkable adaptations of specific cells, organelles and molecules to this extreme environment can provide new perspectives on the processes studied in conventional exp...
journal_title:Nature cell biology
pub_type: 杂志文章
doi:10.1038/ncb0103-3
更新日期:2003-01-01 00:00:00
abstract::The tumour-suppressor gene ATM, mutations in which cause the human genetic disease ataxia telangiectasia (A-T), encodes a key protein kinase that controls the cellular response to DNA double-strand breaks (DSBs). DNA DSBs caused by ionizing radiation or chemicals result in rapid ATM autophosphorylation, leading to che...
journal_title:Nature cell biology
pub_type: 杂志文章
doi:10.1038/ncb1651
更新日期:2007-11-01 00:00:00
abstract:: ...
journal_title:Nature cell biology
pub_type: 评论,杂志文章
doi:10.1038/s41556-018-0224-y
更新日期:2018-11-01 00:00:00
abstract::Breast cancer brain metastasis (BCBM) is a devastating disease. Radiation therapy remains the mainstay for treatment of this disease. Unfortunately, its efficacy is limited by the dose that can be safely applied. One promising approach to overcoming this limitation is to sensitize BCBMs to radiation by inhibiting thei...
journal_title:Nature cell biology
pub_type: 杂志文章
doi:10.1038/s41556-020-00586-6
更新日期:2020-10-01 00:00:00
abstract::Chromosome loss or gain is associated with a large number of solid cancers, providing genomic plasticity and thus adaptability to cancer cells. Numerical centrosome abnormalities arising from centrosome over-duplication or failed cytokinesis are a recognized cause of aneuploidy. In higher eukaryotic cells, the centros...
journal_title:Nature cell biology
pub_type: 杂志文章
doi:10.1038/ncb1735
更新日期:2008-06-01 00:00:00
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 nuc...
journal_title:Nature cell biology
pub_type: 杂志文章
doi:10.1038/ncb2126
更新日期:2010-12-01 00:00:00
abstract::When cells enter mitosis with DNA that is unfit to be segregated, the consequences appear to be loss of centrosome function, abnormal spindles and a failure to segregate chromosomes. These defects may result from the workings of a surveillance mechanism that acts to cull irreparable nuclei. ...
journal_title:Nature cell biology
pub_type: 评论,新闻
doi:10.1038/35000099
更新日期:2000-02-01 00:00:00
abstract::The precise regulation of growth factor signalling is crucial to the molecular control of development in Drosophila. Post-translational modification of signalling molecules is one of the mechanisms that modulate developmental signalling specificity. We describe a new gene, fringe connection (frc), that encodes a nucle...
journal_title:Nature cell biology
pub_type: 杂志文章
doi:10.1038/ncb0901-809
更新日期:2001-09-01 00:00:00
abstract::Small RNAs generated at DNA break sites are implicated in mammalian DNA repair. Now, a study shows that following the formation of DNA double-strand breaks, bidirectional transcription events adjacent to the break generate small RNAs that trigger the DNA damage response by local RNA:RNA interactions. ...
journal_title:Nature cell biology
pub_type: 杂志文章
doi:10.1038/ncb3645
更新日期:2017-11-29 00:00:00
abstract::Plant cell morphogenesis relies on the organization and function of two polymer arrays separated by the plasma membrane: the cortical microtubule cytoskeleton and cellulose microfibrils in the cell wall. Studies using in vivo markers confirmed that one function of the cortical microtubule array is to drive organizatio...
journal_title:Nature cell biology
pub_type: 杂志文章
doi:10.1038/ncb1886
更新日期:2009-07-01 00:00:00
abstract::The genome is organized via CTCF-cohesin-binding sites, which partition chromosomes into 1-5 megabase (Mb) topologically associated domains (TADs), and further into smaller sub-domains (sub-TADs). Here we examined in vivo an ∼80 kb sub-TAD, containing the mouse α-globin gene cluster, lying within a ∼1 Mb TAD. We find ...
journal_title:Nature cell biology
pub_type: 杂志文章
doi:10.1038/ncb3573
更新日期:2017-08-01 00:00:00
abstract::Dyneins are large microtubule motor proteins required for mitosis, intracellular transport and ciliary and flagellar motility. They generate force through a power-stroke mechanism, which is an ATP-consuming cycle of pre- and post-power-stroke conformational changes that cause relative motion between different dynein d...
journal_title:Nature cell biology
pub_type: 杂志文章
doi:10.1038/ncb2939
更新日期:2014-05-01 00:00:00
abstract::BACE1 activity is significantly increased in the brains of Alzheimer's disease patients, potentially contributing to neurodegeneration. The voltage-gated sodium channel (Na(v)1) beta2-subunit (beta2), a type I membrane protein that covalently binds to Na(v)1 alpha-subunits, is a substrate for BACE1 and gamma-secretase...
journal_title:Nature cell biology
pub_type: 杂志文章
doi:10.1038/ncb1602
更新日期:2007-07-01 00:00:00
abstract::Correct placement and orientation of the mitotic spindle is essential for segregation of localized components and positioning of daughter cells. Although these processes are important in many cells, few factors that regulate spindle placement are known. Previous work has shown that GPB-1, the Gbeta subunit of a hetero...
journal_title:Nature cell biology
pub_type: 杂志文章
doi:10.1038/35060092
更新日期:2001-03-01 00:00:00
abstract::Cellular senescence is a tumour suppressor programme characterized by a stable cell cycle arrest. Here we report that cellular senescence triggered by a variety of stimuli leads to diminished ribosome biogenesis and the accumulation of both rRNA precursors and ribosomal proteins. These defects were associated with red...
journal_title:Nature cell biology
pub_type: 杂志文章
doi:10.1038/s41556-018-0127-y
更新日期:2018-07-01 00:00:00
abstract::Cytokinesis requires the spatio-temporal coordination of cell-cycle control and cytoskeletal reorganization. Members of the Rho-family of GTPases are crucial regulators of this process and assembly of the contractile ring depends on local activation of Rho signalling. Here, we show that the armadillo protein p0071, un...
journal_title:Nature cell biology
pub_type: 杂志文章
doi:10.1038/ncb1504
更新日期:2006-12-01 00:00:00
abstract::The actin cable is a supracellular structure that embryonic epithelia produce to close gaps. However, the action of the cable remains debated. Here, we address the function of the cable using Drosophila dorsal closure, a paradigm to understand wound healing. First, we show that the actin cytoskeleton protein Zasp52 is...
journal_title:Nature cell biology
pub_type: 杂志文章
doi:10.1038/ncb3421
更新日期:2016-11-01 00:00:00
abstract::Here we show that segregation of homologous chromosomes and that of sister chromatids are differentially regulated in Xenopus and possibly in other higher eukaryotes. Upon hormonal stimulation, Xenopus oocytes microinjected with antibodies against the anaphase-promoting complex (APC) activator Fizzy or the APC core su...
journal_title:Nature cell biology
pub_type: 杂志文章
doi:10.1038/35050607
更新日期:2001-01-01 00:00:00
abstract::Filament-forming cytoskeletal proteins are essential for the structure and organization of all cells. Bacterial homologues of the major eukaryotic cytoskeletal families have now been discovered, but studies suggest that yet more remain to be identified. We demonstrate that the metabolic enzyme CTP synthase (CtpS) form...
journal_title:Nature cell biology
pub_type: 杂志文章
doi:10.1038/ncb2087
更新日期:2010-08-01 00:00:00
abstract::Accurate chromosome segregation during cell division in metazoans relies on proper chromosome congression at the equator. Chromosome congression is achieved after bi-orientation to both spindle poles shortly after nuclear envelope breakdown, or by the coordinated action of motor proteins that slide misaligned chromoso...
journal_title:Nature cell biology
pub_type: 杂志文章
doi:10.1038/ncb3060
更新日期:2014-12-01 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::Parallel quantification of large numbers of messenger RNA transcripts using microarray technology promises to provide detailed insight into cellular processes involved in the regulation of gene expression. This should allow new understanding of signalling networks that operate in the cell and of the molecular basis an...
journal_title:Nature cell biology
pub_type: 杂志文章,评审
doi:10.1038/35087138
更新日期:2001-08-01 00:00:00
abstract::Only a few RFamide peptides have been identified in mammals, although they have been abundantly found in invertebrates. Here we report the identification of a human gene that encodes at least three RFamide-related peptides, hRFRP-1-3. Cells transfected with a seven-transmembrane-domain receptor, OT7T022, specifically ...
journal_title:Nature cell biology
pub_type: 杂志文章
doi:10.1038/35036326
更新日期:2000-10-01 00:00:00
abstract::Phosphorylation networks intimately regulate mechanisms of response to therapies. Mapping the phospho-catalytic profile of kinases in cells or tissues remains a challenge. Here, we introduce a practical high-throughput system to measure the enzymatic activity of kinases using biological peptide targets as phospho-sens...
journal_title:Nature cell biology
pub_type: 杂志文章
doi:10.1038/s41556-019-0328-z
更新日期:2019-06-01 00:00:00
abstract::Aurora A, an integral mitotic kinase, is essential for microtubule dynamics of post-mitotic neurons. PKCzeta activates Aurora A, which in turn phosphorylates NDEL1 to promote neurite extension. This raises the possibility that Aurora A may also be involved in establishing cell polarity and axon/dendrite elaboration in...
journal_title:Nature cell biology
pub_type: 评论,新闻
doi:10.1038/ncb0909-1053
更新日期:2009-09-01 00:00:00
abstract::Bcl-2 stimulates mutagenesis after the exposure of cells to DNA-damaging agents. However, the biological mechanisms of Bcl-2-mediated mutagenesis have remained largely obscure. Here we demonstrate that the Bcl-2-mediated suppression of hMSH2 expression results in a reduced cellular capacity to repair mismatches. The p...
journal_title:Nature cell biology
pub_type: 杂志文章
doi:10.1038/ncb1215
更新日期:2005-02-01 00:00:00
abstract::Tumour growth and invasiveness require extracellular matrix (ECM) degradation and are stimulated by the GALA pathway, which induces protein O-glycosylation in the endoplasmic reticulum (ER). ECM degradation requires metalloproteases, but whether other enzymes are required is unclear. Here, we show that GALA induces th...
journal_title:Nature cell biology
pub_type: 杂志文章
doi:10.1038/s41556-020-00590-w
更新日期:2020-11-01 00:00:00
abstract::KLF4 (GKLF/EZF) encodes a transcription factor that is associated with both tumour suppression and oncogenesis. We describe the identification of KLF4 in a functional genomic screen for genes that bypass RAS(V12)-induced senescence. However, in untransformed cells, KLF4 acts as a potent inhibitor of proliferation. KLF...
journal_title:Nature cell biology
pub_type: 杂志文章
doi:10.1038/ncb1314
更新日期:2005-11-01 00:00:00
abstract::Formins have been implicated in the regulation of cytoskeletal structure in animals and fungi. Here we show that the formins Bni1 and Bnr1 of budding yeast stimulate the assembly of actin filaments that function as precursors to tropomyosin-stabilized cables that direct polarized cell growth. With loss of formin funct...
journal_title:Nature cell biology
pub_type: 更正并重新发布的文章,杂志文章
doi:10.1038/ncb770
更新日期:2002-03-01 00:00:00
abstract::TP53 (tumour protein 53) is one of the most frequently mutated genes in human cancer and its role during cellular transformation has been studied extensively. However, the homeostatic functions of p53 are less well understood. Here, we explore the molecular dependency network of TP53 through an RNAi-mediated synthetic...
journal_title:Nature cell biology
pub_type: 杂志文章
doi:10.1038/ncb2264
更新日期:2011-06-05 00:00:00