Abstract:
:The p53 inhibitor murine double-minute gene 2 (Mdm2) is a target for potential cancer therapies, however increased p53 function can be lethal. To directly address whether reduced Mdm2 function can inhibit tumorigenesis without causing detrimental side effects, we exploited a hypomorphic murine allele of mdm2 to compare the effects of decreased levels of Mdm2 and hence increased p53 activity on tumorigenesis and life span in mice. Here we report that mice with decreased levels of Mdm2 are resistant to tumor formation yet do not age prematurely, supporting the notion that Mdm2 is a promising target for cancer therapeutics.
journal_name
Genes Devjournal_title
Genes & developmentauthors
Mendrysa SM,O'Leary KA,McElwee MK,Michalowski J,Eisenman RN,Powell DA,Perry MEdoi
10.1101/gad.1378506subject
Has Abstractpub_date
2006-01-01 00:00:00pages
16-21issue
1eissn
0890-9369issn
1549-5477pii
20/1/16journal_volume
20pub_type
杂志文章abstract::Unrepaired DNA lesions in the template strand block the replication fork. In yeast, Mec1 protein kinase-mediated replication checkpoint prevents the breakdown of replication forks and maintains viability in DNA-damaged cells going through the S phase. By ensuring that the replisome does not dissociate from the fork st...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1793409
更新日期:2009-06-15 00:00:00
abstract::Telomerase is a ribonucleoprotein enzyme that adds telomeric repeats to chromosomes, maintaining telomere length and stabilizing chromosome ends. In vitro, telomerase from the ciliate Tetrahymena elongates single-stranded, guanosine-rich DNA primers by adding repeats of the Tetrahymena telomeric sequence, dT2G4. We ha...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.7.7b.1364
更新日期:1993-07-01 00:00:00
abstract::Early endoderm formation in zebrafish requires at least three loci that function downstream of Nodal signaling but upstream of the early endodermal marker sox17: bonnie and clyde (bon), faust (fau), and casanova (cas). cas mutants show the most severe phenotype as they do not form any gut tissue and lack all sox17 exp...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.892301
更新日期:2001-06-15 00:00:00
abstract::Ferredoxin reductase (FDXR), a target of p53, modulates p53-dependent apoptosis and is necessary for steroidogenesis and biogenesis of iron-sulfur clusters. To determine the biological function of FDXR, we generated a Fdxr-deficient mouse model and found that loss of Fdxr led to embryonic lethality potentially due to ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.299388.117
更新日期:2017-06-15 00:00:00
abstract::Transcriptional profiling is a powerful approach for understanding development and disease. Current cell type-specific RNA purification methods have limitations, including cell dissociation trauma or inability to identify all RNA species. Here, we describe "mouse thiouracil (TU) tagging," a genetic and chemical inters...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.205278.112
更新日期:2013-01-01 00:00:00
abstract::The product of the zygotically active decapentaplegic (dpp) gene appears to function as a morphogen that specifies positional information in the dorsal half of the Drosophila embryo. The dorsal-specific transcription of dpp is the key step in establishing a morphogen gradient. We demonstrate here that multiple regions...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.7.4.694
更新日期:1993-04-01 00:00:00
abstract::Experiments in Xenopus have illustrated the importance of extracellular morphogens for embryonic gene regulation in vertebrates. Much less is known about how induction leads to the correct positioning of boundaries; for example, between germ layers. Here we report that the neuroectoderm/mesoderm boundary is controlled...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.409507
更新日期:2007-04-15 00:00:00
abstract::Transabdominal (Tab), a dominant mutation in the Bithorax Complex (BX-C) of Drosophila, creates a sexually dimorphic pattern of segmental transformation that has complete penetrance and expressivity. Specific regions within the notum of the second thoracic segment (T2) are transformed into abdominal-like cuticle; thus...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1.2.111
更新日期:1987-04-01 00:00:00
abstract::The myogenic regulatory factor MyoD dimerizes with other positive and negative regulatory factors through a conserved region called the helix-loop-helix (HLH) domain. Using a non-DNA-binding MyoD mutant with a normal HLH domain as a dimerization competitor in gel mobility shift assays in conjunction with various MyoD ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.7.12a.2456
更新日期:1993-12-01 00:00:00
abstract::The allosteric and torpedo models have been used for 30 yr to explain how transcription terminates on protein-coding genes. The former invokes termination via conformational changes in the transcription complex and the latter proposes that degradation of the downstream product of poly(A) signal (PAS) processing is imp...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.332833.119
更新日期:2020-01-01 00:00:00
abstract::Codon usage bias is a universal feature of all genomes, but its in vivo biological functions in animal systems are not clear. To investigate the in vivo role of codon usage in animals, we took advantage of the sensitivity and robustness of the Drosophila circadian system. By codon-optimizing parts of Drosophila period...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.281030.116
更新日期:2016-08-01 00:00:00
abstract::Transvection can cause the expression of a gene to be sensitive to the proximity of a homolog. It can account for many cases of intragenic complementation at the Drosophila yellow gene, where one mode of transvection involves the action of enhancers in trans on a promoter present on a separate chromosome. Our goal was...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.13.3.253
更新日期:1999-02-01 00:00:00
abstract::A relevant, yet little recognized feature of antisense regulation is the possibility of switching roles between regulatory and regulated RNAs. Here we show that induction of a Salmonella gene relies on the conversion of a small RNA from effector to regulatory target. The chiP gene (formerly ybfM), identified and chara...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.541609
更新日期:2009-09-01 00:00:00
abstract::Although branchpoint recognition is an essential component of intron excision during the RNA splicing process, the branchpoint itself is frequently assumed to be a basal, rather than regulatory, sequence feature. However, this assumption has not been systematically tested due to the technical difficulty of identifying...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.312058.118
更新日期:2018-04-01 00:00:00
abstract::The tobacco mitogen-activated protein kinase (MAPK) cascade, which includes MAPK NRK1/NTF6, positively regulates expansion of the cytokinetic machinery known as the phragmoplast, which is followed by the synthesis of cell plates for completion of cell division. However, molecular events lying between the MAPK and phra...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1408106
更新日期:2006-04-15 00:00:00
abstract::The WD40 domain-containing protein WRAP53β (WD40 encoding RNA antisense to p53; also referred to as WDR79/TCAB1) controls trafficking of splicing factors and the telomerase enzyme to Cajal bodies, and its functional loss has been linked to carcinogenesis, premature aging, and neurodegeneration. Here, we identify WRAP5...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.246546.114
更新日期:2014-12-15 00:00:00
abstract::The daughterless (da) gene is known to have separate maternal and zygotic functions: Maternally supplied daughterless activity is required for proper sex determination and dosage compensation in female embryos, whereas loss of zygotically supplied da+ activity causes embryonic lethality in both male and female embryos...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.2.7.843
更新日期:1988-07-01 00:00:00
abstract::The Bloom's syndrome gene (BLM) plays a pivotal role in the maintenance of genomic stability in somatic cells. It encodes a DNA helicase (BLM) of the RecQ family, but the exact function of BLM remains elusive. To study this question, we have cloned the BLM homolog of the frog Xenopus laevis (xBLM) and have raised anti...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.822400
更新日期:2000-10-15 00:00:00
abstract::The transcription cofactor MAL is regulated by free actin levels and thus by actin dynamics. MAL, together with its DNA-binding partner, SRF, is required for invasive cell migration and in experimental metastasis. Although MAL/SRF has many targets, we provide genetic evidence in both Drosophila and human cellular mode...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.237743.114
更新日期:2014-05-15 00:00:00
abstract::The liver X receptors (LXRs) are members of the nuclear hormone receptor superfamily that are bound and activated by oxysterols. These receptors serve as sterol sensors to regulate the transcription of gene products that control intracellular cholesterol homeostasis through catabolism and transport. In this report, we...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.844900
更新日期:2000-11-15 00:00:00
abstract::In enteric bacteria, the transcription factor σ(E) maintains membrane homeostasis by inducing synthesis of proteins involved in membrane repair and two small regulatory RNAs (sRNAs) that down-regulate synthesis of abundant membrane porins. Here, we describe the discovery of a third σ(E)-dependent sRNA, MicL (mRNA-inte...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.243485.114
更新日期:2014-07-15 00:00:00
abstract::Upon activation by far-red light, phytochrome A signals are transduced through several pathways to promote photomorphogenesis. The COP1 E3 ligase represses photomorphogenesis in part by targeting transcription activators such as LAF1 and HY5 for destruction. Another positive regulator of photomorphogenesis is HFR1, a ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1247205
更新日期:2005-03-01 00:00:00
abstract::FISH analysis of well-spread chromosomes reveals that homologs are paired in vegetatively growing budding yeast diploid cells, via multiple interstitial interactions, and independent of recA homologs and mating type heterozygosity. Pairing is present during G1 and G2, and in cells arrested at G1 by mating pheromone, b...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.13.12.1627
更新日期:1999-06-15 00:00:00
abstract::Histone methylation plays an important role in regulating gene expression. One such methylation occurs at Lys 79 of histone H3 (H3K79) and is catalyzed by the yeast DOT1 (disruptor of telomeric silencing) and its mammalian homolog, DOT1L. Previous studies have demonstrated that germline disruption of Dot1L in mice res...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.2018511
更新日期:2011-02-01 00:00:00
abstract::As in many polarized cells, spindle alignment in yeast is essential and cell cycle regulated. A key step that governs spindle alignment is the selective binding of the Kar9 protein to only one of the two spindle pole bodies (SPBs). It has been suggested that cyclin-dependent kinase Cdc28, in complex with cyclin Clb4, ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.298704
更新日期:2004-07-15 00:00:00
abstract::A powerful enhancer has been mapped to an 18-bp DNA segment located 11 kb 5' to the human epsilon-globin gene within the dominant control or locus-activating region. This enhancer is inducible in K562 human erythroleukemia cells, increasing linked gamma-globin promoter/luciferase gene expression to 170-fold over an en...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.4.6.993
更新日期:1990-06-01 00:00:00
abstract::We isolated a novel bHLH protein gene Mesp2 (for mesoderm posterior 2) that cross-hybridizes with Mesp1 expressed in the early mouse mesoderm. Mesp2 is expressed in the rostral presomitic mesoderm, but down-regulated immediately after the formation of the segmented somites. To determine the function of MesP2 protein (...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.11.14.1827
更新日期:1997-07-15 00:00:00
abstract::Oligophrenin-1 (OPHN1) encodes a Rho-GTPase-activating protein (Rho-GAP) whose loss of function has been associated with X-linked mental retardation (MR). The pathophysiological role of OPHN1, however, remains poorly understood. Here we show that OPHN1 through its Rho-GAP activity plays a critical role in the activity...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1783809
更新日期:2009-06-01 00:00:00
abstract::The visual system is a powerful model for probing the development, connectivity, and function of neural circuits. Two genetically tractable species, mice and flies, are together providing a great deal of understanding of these processes. Current efforts focus on integrating knowledge gained from three cross-fostering ...
journal_title:Genes & development
pub_type: 杂志文章,评审
doi:10.1101/gad.248245.114
更新日期:2014-12-01 00:00:00
abstract::Janus kinase 2 (JAK2) is a central kinase in hematopoietic stem/progenitor cells (HSPCs), and its uncontrolled activation is a prominent oncogenic driver of hematopoietic neoplasms. However, molecular mechanisms underlying the regulation of JAK2 have remained elusive. Here we report that the Casitas B-cell lymphoma (C...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.297135.117
更新日期:2017-05-15 00:00:00