Abstract:
:Transformation of primary rodent cells by the adenovirus E1A and E1B oncogenes is a two-step process, where E1A-dependent induction of proliferation is coupled to E1B-dependent suppression of programmed cell death (apoptosis). The E1B gene encodes two distinct transforming proteins, the 19K and 55K proteins, both of which independently cooperate with E1A. E1B 19K or 55K protein, or the human Bcl-2 protein, functions to suppress apoptosis and thereby permits transformation with E1A. The E1B 55K protein blocks p53 tumor suppressor protein function, indicating that p53 may mediate apoptosis by E1A. In the mutant conformation, p53 blocked induction of apoptosis by E1A and efficiently cooperated with E1A to transform primary cells. When p53 was returned to the wild-type conformation, E1A+p53 transformants underwent cell death by apoptosis. This induction of apoptosis by conformational shift of p53 from the mutant to the wild-type form was inhibited by expression of the E1B 19K protein. Thus, the p53 protein may function as a tumor suppressor by initiating a cell suicide response to deregulation of growth control by E1A. E1B 19K and 55K proteins provide separate mechanisms that disable the cell suicide pathway of p53.
journal_name
Genes Devjournal_title
Genes & developmentauthors
Debbas M,White Edoi
10.1101/gad.7.4.546subject
Has Abstractpub_date
1993-04-01 00:00:00pages
546-54issue
4eissn
0890-9369issn
1549-5477journal_volume
7pub_type
杂志文章abstract::Eukaryotic translation initiation begins with ribosomal recruitment of aminoacylated initiator tRNA (Met-tRNA(Met)(i)) by eukaryotic initiation factor eIF2. In cooperation with eIF3, eIF1, and eIF1A, Met-tRNA(Met)(i)/eIF2/GTP binds to 40S subunits yielding 43S preinitiation complexes that attach to the 5'-terminal reg...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1957510
更新日期:2010-08-15 00:00:00
abstract::Eukaryotic RNAs with premature termination codons (PTCs) are eliminated by nonsense-mediated decay (NMD). While human nonsense RNA degradation can be initiated either by an endonucleolytic cleavage event near the PTC or through decapping, the individual contribution of these activities on endogenous substrates has rem...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.246538.114
更新日期:2014-11-15 00:00:00
abstract::The N-myc gene encodes a putative transcription factor that is thought to function in the regulation of gene expression during cell differentiation and/or growth. To examine the role of N-myc during development, we have used targeted mutagenesis in embryonic stem cells to produce a mouse line that carries an N-myc nul...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.6.12a.2248
更新日期:1992-12-01 00:00:00
abstract::Hypocretin (orexin; Hcrt)-containing neurons of the hypothalamus are essential for the normal regulation of sleep and wake behaviors and have been implicated in feeding, anxiety, depression, and reward. The absence of these neurons causes narcolepsy in humans and model organisms. However, little is known about the mol...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.207654.112
更新日期:2013-03-01 00:00:00
abstract::We have investigated the DNA-binding, oligomerization, and trans-activation functions of isolated segments of murine p53. We find that p53 has two autonomous DNA-binding regions. One domain, from amino acid 280 to 390, forms stable tetramers and binds DNA nonspecifically. The biological significance, if any, of this D...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.7.12b.2575
更新日期:1993-12-01 00:00:00
abstract::The transcription factor TFIIB plays a central role in preinitiation complex assembly, providing a bridge between promoter-bound TFIID and RNA Polymerase II. TFIIB possesses sequence-specific DNA-binding ability and interacts with the TFIIB-recognition element (BRE), present in many promoters. Here we show that the BR...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.206901
更新日期:2001-11-15 00:00:00
abstract::Polycomb response elements (PREs) are specific cis-regulatory sequences needed for transcriptional repression of HOX and other target genes by Polycomb group (PcG) proteins. Among the many PcG proteins known in Drosophila, Pho is the only sequence-specific DNA-binding protein. To gain insight into the function of Pho,...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.377406
更新日期:2006-05-01 00:00:00
abstract::We hypothesized that basic helix-loop-helix (bHLH) MIST1 (BHLHA15) is a "scaling factor" that universally establishes secretory morphology in cells that perform regulated secretion. Here, we show that targeted deletion of MIST1 caused dismantling of the secretory apparatus of diverse exocrine cells. Parietal cells (PC...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.285684.116
更新日期:2017-01-15 00:00:00
abstract::Cells have evolved checkpoint responses to arrest or delay the cell cycle, activate DNA repair networks, or induce apoptosis after genomic perturbation. Cells have also evolved the translesion synthesis processes to tolerate genomic lesions by either error-free or error-prone repair. Here, we show that after a replica...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1043203
更新日期:2003-01-01 00:00:00
abstract::Chk2/hcds1, the human homolog of the Saccharomyces cerevisiae RAD53/SPK1 and Schizosaccharomyces pombe cds1 DNA damage checkpoint genes, encodes a protein kinase that is post-translationally modified after DNA damage. Like its yeast homologs, the Chk2/hCds1 protein phosphorylates Cdc25C in vitro, suggesting that it ar...
journal_title:Genes & development
pub_type: 杂志文章
doi:
更新日期:2000-02-01 00:00:00
abstract::The subdivision of the Drosophila body into distinct terminal and central domains depends on the torso (tor) protein, a putative receptor tyrosine kinase that is active at both ends of the early embryo. We show that the tor protein is uniformly expressed along the surface membrane of early embryos despite its localize...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.3.12b.2025
更新日期:1989-12-01 00:00:00
abstract::Centromeres are maintained epigenetically by the presence of CENP-A, an evolutionarily conserved histone H3 variant, which directs kinetochore assembly and hence centromere function. To identify factors that promote assembly of CENP-A chromatin, we affinity-selected solubilized fission yeast CENP-ACnp1 chromatin. All ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.332536.119
更新日期:2020-02-01 00:00:00
abstract::The nonsense-mediated mRNA decay (NMD) pathway selectively degrades mRNAs harboring premature termination codons (PTCs). Seven genes (smg-1-7, for suppressor with morphological effect on genitalia) that are essential for NMD were originally identified in the nematode Caenorhabditis elegans, and orthologs of these gene...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.417707
更新日期:2007-05-01 00:00:00
abstract::MicF, one of the first chromosomally encoded regulatory small RNAs (sRNAs) to be discovered, was found to modulate the expression of OmpF, an abundant outer membrane protein. Several recent papers have now shown that this is not an isolated case. At least five other sRNAs also regulate the synthesis of outer membrane ...
journal_title:Genes & development
pub_type: 杂志文章,评审
doi:10.1101/gad.1457506
更新日期:2006-09-01 00:00:00
abstract::The Komeda miniature rat Ishikawa (KMI) is a naturally occurring mutant caused by an autosomal recessive mutation mri, which exhibits longitudinal growth retardation. Here we identified the mri mutation as a deletion in the rat gene encoding cGMP-dependent protein kinase type II (cGKII). KMIs showed an expanded growth...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1224204
更新日期:2004-10-01 00:00:00
abstract::Cyclin D1 is part of a cell cycle control node consistently deregulated in most human cancers. However, studies with cyclin D1-null mice indicate that it is dispensable for normal mouse development as well as cell growth in culture. Here, we provide evidence that ras-mediated tumorigenesis depends on signaling pathway...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.12.16.2469
更新日期:1998-08-15 00:00:00
abstract::AMP-activated protein kinase (AMPK) is a sensor of energy status that maintains cellular energy homeostasis. It arose very early during eukaryotic evolution, and its ancestral role may have been in the response to starvation. Recent work shows that the kinase is activated by increases not only in AMP, but also in ADP....
journal_title:Genes & development
pub_type: 杂志文章,评审
doi:10.1101/gad.17420111
更新日期:2011-09-15 00:00:00
abstract::Although MAX is regarded as an obligate dimerization partner for MYC, its function in normal development and neoplasia is poorly defined. We show that B-cell-specific deletion of Max has a modest effect on B-cell development but completely abrogates Eµ-Myc-driven lymphomagenesis. While Max loss affects only a few hund...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.325878.119
更新日期:2019-09-01 00:00:00
abstract::The subdivision of the lateral mesoderm into a visceral (splanchnic) and a somatic layer is a crucial event during early mesoderm development in both arthropod and vertebrate embryos. In Drosophila, this subdivision leads to the differential development of gut musculature versus body wall musculature. Here we report t...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.917101
更新日期:2001-11-01 00:00:00
abstract::During embryonic development in vertebrates, the endoderm becomes patterned along the anteroposterior axis to produce distinct derivatives. How this regulation is controlled is not well understood. We report that the zebrafish hairy/enhancer of split [E(spl)]-related gene her5 plays a critical role in this process. At...
journal_title:Genes & development
pub_type: 杂志文章
doi:
更新日期:2000-07-01 00:00:00
abstract::The eukaryotic ribosomal RNA (rRNA) is associated cotranscriptionally with numerous factors into an enormous 90S preribosomal particle that conducts early processing of small ribosomal subunits. The assembly pathway and structure of the 90S particle is poorly understood. Here, we affinity-purified and analyzed the con...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.274688.115
更新日期:2016-03-15 00:00:00
abstract::Genomic imprinting, an inherently epigenetic phenomenon defined by parent of origin-dependent gene expression, is observed in mammals and flowering plants. Genome-scale surveys of imprinted expression and the underlying differential epigenetic marks have led to the discovery of hundreds of imprinted plant genes and co...
journal_title:Genes & development
pub_type: 杂志文章,评审
doi:10.1101/gad.269902.115
更新日期:2015-12-15 00:00:00
abstract::The yeast SAGA (Spt-Ada-Gcn5-acetyltransferase) coactivator complex exerts functions in gene expression, including activator interaction, histone acetylation, histone deubiquitination, mRNA export, chromatin recognition, and regulation of the basal transcription machinery. These diverse functions involve distinct modu...
journal_title:Genes & development
pub_type: 杂志文章,评审
doi:10.1101/gad.184705.111
更新日期:2012-03-15 00:00:00
abstract::Cell growth and differentiation are usually antagonistic. Proteins of the basic helix-loop-helix (bHLH) family bind DNA and play important roles in the differentiation of specific cell types. Id proteins heterodimerize with bHLH transcription factors, blocking their activation of lineage-specific gene expression and t...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.8.11.1270
更新日期:1994-06-01 00:00:00
abstract::Gene dosage alterations caused by aneuploidy are a common feature of most cancers yet pose severe proteotoxic challenges. Therefore, cells have evolved various dosage compensation mechanisms to limit the damage caused by the ensuing protein level imbalances. For instance, for heteromeric protein complexes, excess nons...
journal_title:Genes & development
pub_type: 评论
doi:10.1101/gad.329383.119
更新日期:2019-08-01 00:00:00
abstract::C-factor, the product of the csgA gene, is a cell-surface associated short-range intercellular signaling protein in Myxococcus xanthus. C-factor is required for at least four responses during starvation-induced fruiting body morphogenesis: rippling, aggregation, sporulation, and full expression of the csgA gene, all o...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.10.6.740
更新日期:1996-03-15 00:00:00
abstract::AAUAAA is the most highly conserved motif in eukaryotic mRNA polyadenylation sites and, in mammals, is specifically recognized by the multisubunit CPSF (cleavage and polyadenylation specificity factor) complex. Despite its critical functions in mRNA 3' end formation, the molecular basis for CPSF-AAUAAA interaction rem...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.250993.114
更新日期:2014-11-01 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 E2F transcription factor is required for S phase in Drosophila. While it also triggers expression of replication genes at the G1-S transition, the relevance of this transcription is not clear because many of the induced gene products are sufficiently stable that new expression is not required for S phase. However,...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.9.12.1456
更新日期:1995-06-15 00:00:00
abstract::A key pathway that controls both cell division and differentiation in animal cells is mediated by the retinoblastoma (RB) family of tumor suppressors, which gate the passage of cells from G(1) to S and through S phase. The role(s) of the RB pathway in plants are not yet clearly defined, nor has there been any evidence...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.892101
更新日期:2001-07-01 00:00:00