Abstract:
:The p53 protein can inhibit cell cycling or induce apoptosis, and is thus a critical regulator of tumorigenesis. This protein is negatively regulated by a physical interaction with MDM2, an E3 ubiquitin ligase. This interaction is critical for cell viability; loss of Mdm2 causes cell death in vitro and in vivo in a p53-dependent manner. The recently discovered MDM2-related protein MDM4 (also known as MDMX) has some of the same properties as MDM2. MDM4 binds and inhibits p53 transcriptional activity in vitro. Unlike MDM2, however, MDM4 does not cause nuclear export or degradation of p53 (refs. 9,10). To study MDM4 function in vivo, we deleted Mdm4 in mice. Mdm4-null mice died at 7.5-8.5 dpc, owing to loss of cell proliferation and not induction of apoptosis. To assess the importance of p53 in the death of Mdm4-/- embryos, we crossed in the Trp53-null allele. The loss of Trp53 completely rescued the Mdm4-/- embryonic lethality. Thus, MDM2 and MDM4 are nonoverlapping critical regulators of p53 in vivo. These data define a new pathway of p53 regulation and raise the possibility that increased MDM4 levels and the resulting inactivation of p53 contribute to the development of human tumors.
journal_name
Nat Genetjournal_title
Nature geneticsauthors
Parant J,Chavez-Reyes A,Little NA,Yan W,Reinke V,Jochemsen AG,Lozano Gdoi
10.1038/ng714keywords:
subject
Has Abstractpub_date
2001-09-01 00:00:00pages
92-5issue
1eissn
1061-4036issn
1546-1718pii
ng714journal_volume
29pub_type
杂志文章相关文献
NATURE GENETICS文献大全abstract::Despite the clinical significance of balanced chromosomal abnormalities (BCAs), their characterization has largely been restricted to cytogenetic resolution. We explored the landscape of BCAs at nucleotide resolution in 273 subjects with a spectrum of congenital anomalies. Whole-genome sequencing revised 93% of karyot...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng.3720
更新日期:2017-01-01 00:00:00
abstract::Transcription of the 2.5 megabase dystrophin gene gives rise to multiple isoforms. We describe a 5.2 kilobase transcript, expressed specifically in peripheral nerve, that initiates at a previously unrecognized exon located approximately 850 basepairs upstream of dystrophin exon 56. The likely product of this transcrip...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng0593-77
更新日期:1993-05-01 00:00:00
abstract::The T-cell receptor (TCR) is composed of two glycoproteins (alpha and beta or gamma and delta) associated with four invariant polypeptides (CD3-gamma, delta, epsilon and zeta). The majority of TCR/CD3 complexes contain six polypeptide chains, and although there is some flexibility in the complex subunit stoichiometry ...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng0193-77
更新日期:1993-01-01 00:00:00
abstract::Autosomal dominant polycystic kidney disease (ADPKD) describes a group of at least three genetically distinct disorders with almost identical clinical features that collectively affects 1:1,000 of the population. Affected individuals typically develop large cystic kidneys and approximately one half develop end-stage r...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng0697-179
更新日期:1997-06-01 00:00:00
abstract::The basic helix-loop-helix (bHLH) transcription factors, Hand1 and Hand2 (refs 1,2), also called eHand/Hxt/Thing1 and dHand/Hed/Thing2 (refs 3,4), respectively, are expressed in the heart and certain neural-crest derivatives during embryogenesis. In addition, Hand1 is expressed in extraembryonic membranes, whereas Han...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng0398-266
更新日期:1998-03-01 00:00:00
abstract::Obesity is globally prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined associations between body mass index and ∼ 2.8 million SNPs in up to 123,865 individuals with targeted follow up of 42 SNPs in up to 125,931 ad...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng.686
更新日期:2010-11-01 00:00:00
abstract::Extremes of the electrocardiographic QT interval, a measure of cardiac repolarization, are associated with increased cardiovascular mortality. We identified a common genetic variant influencing this quantitative trait through a genome-wide association study on 200 subjects at the extremes of a population-based QT inte...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng1790
更新日期:2006-06-01 00:00:00
abstract::Recent agreement on stable reference sequences for reporting human genetic variants now allows us to mandate the use of the allele naming conventions developed by the Human Genome Variation Society. ...
journal_title:Nature genetics
pub_type: 社论
doi:10.1038/ng0510-363
更新日期:2010-05-01 00:00:00
abstract::G protein-coupled receptors (GPCRs) participate in the most common signal transduction system at the plasma membrane. The wide distribution of heterotrimeric G proteins in the internal membranes suggests that a similar signalling mechanism might also be used at intracellular locations. We provide here structural evide...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/12715
更新日期:1999-09-01 00:00:00
abstract::We identified association of restless legs syndrome (RLS) with PTPRD at 9p23-24 in 2,458 affected individuals and 4,749 controls from Germany, Austria, Czechia and Canada. Two independent SNPs in the 5' UTR of splice variants expressed predominantly in the central nervous system showed highly significant P values (rs4...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng.190
更新日期:2008-08-01 00:00:00
abstract::Antimalarial drugs impose strong selective pressure on Plasmodium falciparum parasites and leave signatures of selection in the parasite genome; screening for genes under selection may suggest potential drug or immune targets. Genome-wide association studies (GWAS) of parasite traits have been hampered by the lack of ...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng.528
更新日期:2010-03-01 00:00:00
abstract::Schistosoma mansoni is the primary causative agent of schistosomiasis, which affects 200 million individuals in 74 countries. We generated 163,000 expressed-sequence tags (ESTs) from normalized cDNA libraries from six selected developmental stages of the parasite, resulting in 31,000 assembled sequences and 92% sampli...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng1237
更新日期:2003-10-01 00:00:00
abstract::The Escherichia coli gene recQ was identified as a RecF recombination pathway gene. The gene SGS1, encoding the only RecQ-like DNA helicase in Saccharomyces cerevisiae, was identified by mutations that suppress the top3 slow-growth phenotype. Relatively little is known about the function of Sgs1p because single mutati...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/83673
更新日期:2001-01-01 00:00:00
abstract::To further understanding of the genetic basis of type 2 diabetes (T2D) susceptibility, we aggregated published meta-analyses of genome-wide association studies (GWAS), including 26,488 cases and 83,964 controls of European, east Asian, south Asian and Mexican and Mexican American ancestry. We observed a significant ex...
journal_title:Nature genetics
pub_type: 杂志文章,meta分析
doi:10.1038/ng.2897
更新日期:2014-03-01 00:00:00
abstract::We identified three distinct mutations and six mutant alleles in GDAP1 in three families with axonal Charcot-Marie-Tooth (CMT) neuropathy and vocal cord paresis, which were previously linked to the CMT4A locus on chromosome 8q21.1. These results establish the molecular etiology of CMT4A (MIM 214400) and suggest that i...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng798
更新日期:2002-01-01 00:00:00
abstract::We conducted a genome-wide association study on 969 bladder cancer cases and 957 controls from Texas. For fast-track validation, we evaluated 60 SNPs in three additional US populations and validated the top SNP in nine European populations. A missense variant (rs2294008) in the PSCA gene showed consistent association ...
journal_title:Nature genetics
pub_type: 信件
doi:10.1038/ng.421
更新日期:2009-09-01 00:00:00
abstract::Immunotherapy for metastatic colorectal cancer is effective only for mismatch repair-deficient tumors with high microsatellite instability that demonstrate immune infiltration, suggesting that tumor cells can determine their immune microenvironment. To understand this cross-talk, we analyzed the transcriptome of 91,10...
journal_title:Nature genetics
pub_type: 杂志文章,多中心研究
doi:10.1038/s41588-020-0636-z
更新日期:2020-06-01 00:00:00
abstract::The apolipoprotein E (APOE) E4 allele is associated with Alzheimer's disease, cardiovascular disease, and decreased longevity. To probe the mechanism of these associations, cell lines were created which secrete each apoE isoform. ApoE conditioned media, purified apoE, and commercially obtained apoE protected B12 cells...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng0996-55
更新日期:1996-09-01 00:00:00
abstract::Genetic studies of complex traits have mainly identified associations with noncoding variants. To further determine the contribution of regulatory variation, we combined whole-genome and transcriptome data for 624 individuals from Sardinia to identify common and rare variants that influence gene expression and splicin...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng.3840
更新日期:2017-05-01 00:00:00
abstract::We report the first identified mutation in the gene encoding human cytochrome c (CYCS). Glycine 41, invariant throughout eukaryotes, is substituted by serine in a family with autosomal dominant thrombocytopenia caused by dysregulated platelet formation. The mutation yields a cytochrome c variant with enhanced apoptoti...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng.103
更新日期:2008-04-01 00:00:00
abstract::Follicle stimulating hormone (FSH) is a member of the glycoprotein hormone family that includes luteinzing hormone (LH), thyroid stimulating hormone, and chorionic gonadotropin. These heterodimeric hormones share a common alpha subunit and differ in their hormone-specific beta subunit. The biological activity is confe...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng0297-201
更新日期:1997-02-01 00:00:00
abstract::Imprinted genes show differential expression between maternal and paternal alleles as a consequence of epigenetic modification that can result in 'parent-of-origin' effects on phenotypic traits. There is increasing evidence from mouse and human studies that imprinted genes may influence behavior and cognitive function...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng1577
更新日期:2005-06-01 00:00:00
abstract::Transcriptome-wide association studies using predicted expression have identified thousands of genes whose locally regulated expression is associated with complex traits and diseases. In this work, we show that linkage disequilibrium induces significant gene-trait associations at non-causal genes as a function of the ...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/s41588-019-0367-1
更新日期:2019-04-01 00:00:00
abstract::Advances in sequencing technologies have enabled the identification of mutations acquired by bacterial pathogens during infection. However, it remains unclear whether adaptive mutations fix in the population or lead to pathogen diversification within the patient. Here we study the genotypic diversity of Burkholderia d...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng.2848
更新日期:2014-01-01 00:00:00
abstract::Overgrowth disorders are a heterogeneous group of conditions characterized by increased growth parameters and other variable clinical features such as intellectual disability and facial dysmorphism. To identify new causes of human overgrowth, we performed exome sequencing in ten proband-parent trios and detected two d...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng.2917
更新日期:2014-04-01 00:00:00
abstract::Haematopoietic development is regulated by nuclear protein complexes that coordinate lineage-specific patterns of gene expression. Targeted mutagenesis in embryonic stem cells and mice has revealed roles for the X-linked gene Gata1 in erythrocyte and megakaryocyte differentiation. GATA-1 is the founding member of a fa...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/73480
更新日期:2000-03-01 00:00:00
abstract::Acute intermittent porphyria (AIP) is a human disease resulting from a dominantly inherited partial deficiency of the heme biosynthetic enzyme, porphobilinogen deaminase (PBGD). The frequency of the trait for AIP is 1/10,000 in most populations, but may be markedly higher (1/500) in psychiatric patients. The clinical ...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng0296-195
更新日期:1996-02-01 00:00:00
abstract::Reduced lung function predicts mortality and is key to the diagnosis of chronic obstructive pulmonary disease (COPD). In a genome-wide association study in 400,102 individuals of European ancestry, we define 279 lung function signals, 139 of which are new. In combination, these variants strongly predict COPD in indepe...
journal_title:Nature genetics
pub_type: 杂志文章,meta分析
doi:10.1038/s41588-018-0321-7
更新日期:2019-03-01 00:00:00
abstract::We report the first annotated chromosome-level reference genome assembly for pea, Gregor Mendel's original genetic model. Phylogenetics and paleogenomics show genomic rearrangements across legumes and suggest a major role for repetitive elements in pea genome evolution. Compared to other sequenced Leguminosae genomes,...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/s41588-019-0480-1
更新日期:2019-09-01 00:00:00
abstract::Differences in three-dimensional (3D) chromatin architecture can influence the integrity of topologically associating domains (TADs) and rewire specific enhancer-promoter interactions, impacting gene expression and leading to human disease. Here we investigate the 3D chromatin architecture in T cell acute lymphoblasti...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/s41588-020-0602-9
更新日期:2020-04-01 00:00:00