Abstract:
:The MMTVD/myc transgenic mice spontaneously develop oligoclonal CD4+CD8+ T-cell tumors. We used provirus insertional mutagenesis in these mice to identify putative collaborators of c-myc. We found that Notch1 was mutated in a high proportion (52%) of these tumors. Proviruses were inserted upstream of the exon coding for the transmembrane domain and in both transcriptional orientations. These mutations led to high expression of truncated Notch1 RNAs and proteins (86-110 kD). In addition, many Notch1-rearranged tumors showed elevated levels of full-length Notch1 transcripts, whereas nearly all showed increased levels of full-length (330-kD) or close to full-length (280-kD) Notch1 proteins. The 5' end of the truncated RNAs were determined for some tumors by use of RT-PCR and 5' RACE techniques. Depending on the orientation of the proviruses, viral LTR or cryptic promoters appeared to be utilized, and coding potential began in most cases in the transmembrane domain. Pulse-chase experiments revealed that the 330-kD Notch1 proteins were processed into 110- and 280-kD cleavage products. These results suggest that Notch1 can be a frequent collaborator of c-myc for oncogenesis. Furthermore, our data indicate that Notch1 alleles mutated by provirus insertion can lead to increased expression of truncated and full-length (330/280-kD) Notch1 proteins, both being produced in a cleaved and uncleaved form.
journal_name
Genes Devjournal_title
Genes & developmentauthors
Girard L,Hanna Z,Beaulieu N,Hoemann CD,Simard C,Kozak CA,Jolicoeur Pdoi
10.1101/gad.10.15.1930subject
Has Abstractpub_date
1996-08-01 00:00:00pages
1930-44issue
15eissn
0890-9369issn
1549-5477journal_volume
10pub_type
杂志文章abstract::In this issue of Genes & Development, Abruzzi et al. (pp. 2374-2386) use chromatin immunoprecipitation (ChIP) tiling array assays (ChIP-chip) to show that physical interactions between circadian (≅24-h) clock machineries and genomes are more widespread than previously thought and provide novel insights into how clocks...
journal_title:Genes & development
pub_type: 评论,杂志文章
doi:10.1101/gad.180984.111
更新日期:2011-11-15 00:00:00
abstract::Interruption of translation in Escherichia coli can lead to the addition of an 11-residue carboxy-terminal peptide tail to the nascent chain. This modification is mediated by SsrA RNA (also called 10Sa RNA and tmRNA) and marks the tagged polypeptide for proteolysis. Degradation in vivo of lambda repressor amino-termin...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.12.9.1338
更新日期:1998-05-01 00:00:00
abstract::Animals alter their reproductive programs to accommodate changes in nutrient availability, yet the connections between known nutrient-sensing systems and reproductive programs are underexplored, and whether there is a mechanism that senses nucleotide levels to coordinate germline proliferation is unknown. We establish...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.275107.115
更新日期:2016-02-01 00:00:00
abstract::Long understood as a bona fide tumor suppressor that safeguards the integrity of the genome via regulating numerous cellular outcomes, p53 may also exert its decisive and versatile functions by controlling DNA methylation. In this issue of Genes & Development, Tovy and colleagues (pp. 959-972) report that, in naïve mo...
journal_title:Genes & development
pub_type: 评论,杂志文章,评审
doi:10.1101/gad.302364.117
更新日期:2017-05-15 00:00:00
abstract::The reelin (reln) and disabled 1 (dab1) genes both ensure correct neuronal positioning during brain development. We have found that the intracellular Dab1 protein receives a tyrosine phosphorylation signal from extracellular Reln protein. Genetic analysis shows that reln function depends on dab1, and vice versa, as ex...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.13.6.643
更新日期:1999-03-15 00:00:00
abstract::Alternative polyadenylation (APA) is widespread in neuronal development and activity-mediated neural plasticity. However, the underlying molecular mechanisms are largely unknown. We used systematic genetic studies and genome-wide surveys of the transcriptional landscape to identify a context-dependent regulatory pathw...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.266650.115
更新日期:2015-11-15 00:00:00
abstract::The NF-kappa B transcription factor complex is comprised of two subunits, p50 and p65, that share significant homology to the rel oncogene. We have isolated a cDNA encoding a novel 66-kD rel-related protein, designated I-Rel. Unlike other rel-related proteins, I-Rel does not interact with DNA. I-Rel forms heterodimers...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.6.5.745
更新日期:1992-05-01 00:00:00
abstract::In mitosis, the spindle checkpoint protein Mad2 averts aneuploidy by delaying anaphase onset until chromosomes align. Here we show that depletion of Mad2 in meiosis I mouse oocytes induced an increased incidence of aneuploidy. Proteolysis of cyclin B and securin commenced earlier in Mad2-depleted oocytes, resulting in...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.328105
更新日期:2005-01-15 00:00:00
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journal_title:Genes & development
pub_type: 杂志文章,评审
doi:10.1101/gad.335679.119
更新日期:2020-04-01 00:00:00
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journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.6.6.1082
更新日期:1992-06-01 00:00:00
abstract::The mechanisms that control energy homeostasis and tissue growth during development are closely linked through the insulin signal transduction pathway. Changes in the level of insulin and other hormones reflect the nutritional status of the animal to control circulating sugar levels and fat metabolism. Systemic defect...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.374406
更新日期:2006-02-15 00:00:00
abstract::TDP-43 is a critical RNA-binding factor associated with pre-mRNA splicing in mammals. Its expression is tightly autoregulated, with loss of this regulation implicated in human neuropathology. We demonstrate that TDP-43 overexpression in humans and mice activates a 3' untranslated region (UTR) intron, resulting in exci...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.194829.112
更新日期:2012-08-01 00:00:00
abstract::Mutations that influence lin-12 activity in Caenorhabditis elegans may identify conserved factors that regulate the activity of lin-12/Notch proteins. We describe genetic evidence indicating that sel-10 is a negative regulator of lin-12/Notch-mediated signaling in C. elegans. Sequence analysis shows that SEL-10 is a m...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.11.23.3182
更新日期:1997-12-01 00:00:00
abstract::In the cytoplasm of oocytes and early embryos, addition of poly(A) to mRNAs can activate their translation. We demonstrate that despite many differences between poly(A) addition in the cytoplasm and nucleus, these two forms of polyadenylation may involve identical trans-acting factors. Nuclear polyadenylation requires...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.8.9.1106
更新日期:1994-05-01 00:00:00
abstract::The empty spiracles (ems) homeo box gene is required for the development of the Drosophila larval filzkörper, which are structural specializations of the eighth abdominal segment. Filzkörper development is also dependent on the function of the homeotic selector gene Abdominal-B (Abd-B). Here, we show that ems is a dow...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.7.2.229
更新日期:1993-02-01 00:00:00
abstract::Two independent two-dimensional (2D) gel methods were used to map an origin of replication that is developmentally regulated by the steroid hormone ecdysone, namely an origin for DNA puff amplification in the fungus fly Sciara coprophila. Initiation of replication was found to occur within a small region of no larger ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.7.6.1072
更新日期:1993-06-01 00:00:00
abstract::Genomic imprinting is essential for mammalian development. Recent studies have revealed that maternal histone H3 Lys27 trimethylation (H3K27me3) can mediate DNA methylation-independent genomic imprinting. However, the regulatory mechanisms and functions of this new imprinting mechanism are largely unknown. Here we dem...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.318675.118
更新日期:2018-12-01 00:00:00
abstract::Faithful duplication of the genome relies on the ability to cope with an imperfect template. We investigated replication of UV-damaged DNA in Escherichia coli and found that ongoing replication stops for at least 15-20 min before resuming. Undamaged origins of replication (oriC) continue to fire at the normal rate and...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.417607
更新日期:2007-03-15 00:00:00
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journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.284828.116
更新日期:2016-08-15 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::Signals from TGF-beta superfamily receptors are transduced to the nucleus by Smad proteins, which transcriptionally activate target genes. In Caenorhabditis elegans, defects in a TGF-beta-related pathway cause a reversible developmental arrest and metabolic shift at the dauer larval stage. Null mutations in daf-3 supp...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.11.20.2679
更新日期:1997-10-15 00:00:00
abstract::We describe here a new murine homeo box gene, denoted Hlx, which is expressed within specific hematopoietic lineages. The cDNA sequence indicates that Hlx differs markedly from known vertebrate homeo box genes, and linkage analysis of an interspecific murine backcross showed that it resides at a novel homeo box locus ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.5.4.509
更新日期:1991-04-01 00:00:00
abstract::The human RNA polymerase II (RNAPII)-associated factor complex (hPAFc) and its individual subunits have been implicated in human diseases, including cancer. However, its involvement in breast cancer awaits investigation. Using data mining and human breast cancer tissue microarrays, we found that Ctr9, the key scaffold...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.268722.115
更新日期:2015-10-15 00:00:00
abstract::We demonstrate here that the previously described bacterial promoter upstream element (UP element) consists of two distinct subsites, each of which, by itself, can bind the RNA polymerase holoenzyme alpha subunit carboxy-terminal domain (RNAP alphaCTD) and stimulate transcription. Using binding-site-selection experime...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.13.16.2134
更新日期:1999-08-15 00:00:00
abstract::Ribonucleotide reductase activity is essential for progression through the cell cycle, catalyzing the rate-limiting step for the production of deoxyribonucleotides needed for DNA synthesis. The enzymatic activity of the enzyme fluctuates in the cell cycle with an activity maximum in S phase. We have identified and cha...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.4.5.740
更新日期:1990-05-01 00:00:00
abstract::Telomeres are specialized nucleoprotein structures that protect chromosome ends from DNA damage response (DDR) and DNA rearrangements. The telomeric shelterin protein TRF2 suppresses the DDR, and this function has been attributed to its abilities to trigger t-loop formation or prevent massive decompaction and loss of ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.294082.116
更新日期:2017-03-15 00:00:00
abstract::We identify the "M region" of the muscle-specific Xenopus cardiac actin gene promoter from -282 to -348 as necessary for the embryonic expression of a cardiac actin-beta-globin reporter gene injected into fertilized eggs. Four DNA-binding activities in embryo extracts, embryonic M-region factors 1-4 (EMF1-4), are desc...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.5.7.1149
更新日期:1991-07-01 00:00:00
abstract::Apoptosis is an important mechanism to eliminate potentially tumorigenic cells. The tumor suppressor p53 plays a pivotal role in this process. Many tumors harbor mutant p53, but others evade its tumor-suppressive effects by altering the expression of proteins that regulate the p53 pathway. ASPP1 (apoptosis-stimulating...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1954410
更新日期:2010-11-01 00:00:00
abstract::A new gene, SCH9, was isolated from Saccharomyces cerevisiae by its ability to complement a cdc25ts mutation. Sequence analysis indicates that it encodes a 90,000-dalton protein with a carboxy-terminal domain homologous to yeast and mammalian cAMP-dependent protein kinase catalytic subunits. In addition to suppressing...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.2.5.517
更新日期:1988-05-01 00:00:00
abstract::Mice mutant for the bHLH gene Hes1, which is known to keep cells in a proliferative state, mostly lack thymus. Transfer of Hes1-null fetal liver cells into RAG2-null host mice normally reconstitutes B cells but fails to generate mature T cells in the thymus. In the reconstituted thymus, T cell differentiation is arres...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.13.9.1203
更新日期:1999-05-01 00:00:00