Abstract:
:The spectrum of tumors associated with oncogenic Ras in humans often differs from those in mice either treated with carcinogens or engineered to sporadically express oncogenic Ras, suggesting that the mechanism of Ras transformation may be different in humans. Ras stimulates primarily three main classes of effector proteins, Rafs, PI3-kinase, and RalGEFs, with Raf generally being the most potent at transforming murine cells. Using oncogenic Ras mutants that activate single effectors as well as constitutively active effectors, we find that the RalGEF, and not the Raf or PI3-kinase pathway, is sufficient for Ras transformation in human cells. Thus, oncogenic Ras may transform murine and human cells by distinct mechanisms, and the RalGEF pathway--previously deemed to play a secondary role in Ras transformation--could represent a new target for anti-cancer therapy.
journal_name
Genes Devjournal_title
Genes & developmentauthors
Hamad NM,Elconin JH,Karnoub AE,Bai W,Rich JN,Abraham RT,Der CJ,Counter CMdoi
10.1101/gad.993902subject
Has Abstractpub_date
2002-08-15 00:00:00pages
2045-57issue
16eissn
0890-9369issn
1549-5477journal_volume
16pub_type
杂志文章,评审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 Swi/Snf chromatin remodeling complex functions to alter nucleosome positions by either sliding nucleosomes on DNA or the eviction of histones. The presence of histone acetylation and activator-dependent recruitment and retention of Swi/Snf is important for its efficient function. It is not understood, however, why...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.243584.114
更新日期:2014-10-15 00:00:00
abstract::Transcription of frog rDNA by mouse cell factors is the only documented exception to the observed species selectivity of rRNA gene expression. This heterologous transcription is authentic in that it uses the normal frog upstream and core promoter domains, as well as the normal mouse polymerase I transcription factors,...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.4.1.52
更新日期:1990-01-01 00:00:00
abstract::The Tat protein of human immunodeficiency virus type 1 (HIV-1) activates transcription following binding to nascent trans-activation response (TAR) RNA downstream of the transcription start site. Because Tat functions when bound to RNA, and in a position-dependent manner, it has been proposed that Tat works by a novel...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.5.12b.2496
更新日期:1991-12-01 00:00:00
abstract::Cellular senescence limits proliferation of potentially detrimental cells, preventing tumorigenesis and restricting tissue damage. However, the function of senescence in nonpathological conditions is unknown. We found that the human placental syncytiotrophoblast exhibited the phenotype and expressed molecular markers ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.227512.113
更新日期:2013-11-01 00:00:00
abstract::Several previously known transcription cofactors have been demonstrated in vitro recently to be histone acetyltransferases and deacetyltransferases, suggesting that remodeling of chromatin through histone acetylation plays a fundamental role in gene regulation. Clear evidence has not yet been obtained, however, to dem...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.12.5.640
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abstract::Wingless (Wg) is an important signaling molecule in the development of Drosophila, but little is known about its signal transduction pathway. Genetic evidence indicates that another segment polarity gene, dishevelled (dsh) is required for Wg signaling. We have recently developed a cell culture system for Wg protein ac...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.9.9.1087
更新日期:1995-05-01 00:00:00
abstract::Cell cycle progression is dependent on two major waves of gene expression. Early cell cycle gene expression occurs during G1/S to generate factors required for DNA replication, while late cell cycle gene expression begins during G2 to prepare for mitosis. Here we demonstrate that the MuvB complex-comprised of LIN9, LI...
journal_title:Genes & development
pub_type: 杂志文章
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更新日期:2012-03-01 00:00:00
abstract::Gene duplication and divergence is a major driver in the emergence of evolutionary novelties. How variations in amino acid sequences lead to loss of ancestral activity and functional diversification of proteins is poorly understood. We used cross-species functional analysis of Drosophila Labial and its mouse HOX1 orth...
journal_title:Genes & development
pub_type: 杂志文章
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更新日期:2020-12-01 00:00:00
abstract::The presence of Set2-mediated methylation of H3K36 (K36me) correlates with transcription frequency throughout the yeast genome. K36me targets the Rpd3S complex to deacetylate transcribed regions and suppress cryptic transcription initiation at certain genes. Here, using a genome-wide approach, we report that the Set2-...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1539307
更新日期:2007-06-01 00:00:00
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journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.2.5.567
更新日期:1988-05-01 00:00:00
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journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1675708
更新日期:2008-08-15 00:00:00
abstract::To define the functional pathways regulating epithelial cell migration, we performed a genome-wide RNAi screen using 55,000 pooled lentiviral shRNAs targeting ∼11,000 genes, selecting for transduced cells with increased motility. A stringent validation protocol generated a set of 31 genes representing diverse pathways...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1989110
更新日期:2010-12-01 00:00:00
abstract::Post-translational modifications of histones are significant regulators of replication, transcription, and DNA repair. Particularly, newly synthesized histone H4 in H3/H4 heterodimers becomes acetylated on N-terminal lysine residues prior to its incorporation into chromatin. Previous studies have established that the ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.240531.114
更新日期:2014-06-01 00:00:00
abstract::The removal of the 5' cap structure by the decapping enzyme DCP2 inhibits translation and generally commits the mRNA to irreversible 5'-to-3' exonucleolytic degradation by XRN1. DCP2 catalytic activity is stimulated by DCP1, and these proteins form the conserved core of the decapping complex. Additional decapping fact...
journal_title:Genes & development
pub_type: 杂志文章,评审
doi:10.1101/gad.227843.113
更新日期:2013-12-15 00:00:00
abstract::Stem cells do not all respond the same way, but the mechanisms underlying this heterogeneity are not well understood. Here, we found that expression of Hes1 and its downstream genes oscillate in mouse embryonic stem (ES) cells. Those expressing low and high levels of Hes1 tended to differentiate into neural and mesode...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1823109
更新日期:2009-08-15 00:00:00
abstract::Entry into sporulation by the Gram-positive bacterium Bacillus subtilis is governed by two transcription factors, Spo0A and sigma H, and involves a switch in the site of division from a medial to a polar location. We report that at the onset of sporulation, assembly of the cell division protein FtsZ shifts from midcel...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.10.4.478
更新日期:1996-02-15 00:00:00
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::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::DBP (albumin D-site-binding protein), HLF (hepatic leukemia factor), and TEF (thyrotroph embryonic factor) are the three members of the PAR bZip (proline and acidic amino acid-rich basic leucine zipper) transcription factor family. All three of these transcriptional regulatory proteins accumulate with robust circadian...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.301404
更新日期:2004-06-15 00:00:00
abstract::One of the most common microsatellites in eukaryotes consists of tandem arrays of the dinucleotide GT. Although the study of the instability of such repetitive DNA has been extremely fruitful over the last decade, no biological function has been demonstrated for these sequences. We investigated the genetic behavior of...
journal_title:Genes & development
pub_type: 杂志文章
doi:
更新日期:2000-05-15 00:00:00
abstract::The senescence-associated secretory phenotype (SASP) is a major trait of senescent cells, but the molecular regulators of SASP factor secretion are poorly understood. Mass spectrometry analysis revealed that secretory carrier membrane protein 4 (SCAMP4) levels were strikingly elevated on the surface of senescent cells...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.313270.118
更新日期:2018-07-01 00:00:00
abstract::TP53 is the most frequently mutated gene in human cancer. Many mutant p53 proteins exert oncogenic gain-of-function (GOF) properties that contribute to metastasis, but the mechanisms mediating these functions remain poorly defined in vivo. To elucidate how mutant p53 GOF drives metastasis, we developed a traceable som...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.304972.117
更新日期:2017-09-15 00:00:00
abstract::The p53 tumor suppressor protein is the most well studied as a regulator of transcription in the nucleus, where it exists primarily as a tetramer. However, there are other oligomeric states of p53 that are relevant to its regulation and activities. In unstressed cells, p53 is normally held in check by MDM2 that target...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.304071.117
更新日期:2018-03-01 00:00:00
abstract::Influenza virus unspliced NS1 mRNA, like retroviral pre-mRNAs, is efficiently exported from the nucleus and translated in the cytoplasm of infected cells. With human immunodeficiency virus (HIV), the transport of viral pre-mRNAs is facilitated by the viral Rev protein. We tested the possibility that the influenza viru...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.6.2.255
更新日期:1992-02-01 00:00:00
abstract::Stomata are specialized cellular structures in the epidermis of aerial plant organs that control gas exchange (H(2)O release and CO(2) uptake) between leaves and the atmosphere by modulating the aperture of a pore flanked by two guard cells. Stomata are nonrandomly distributed, and their density is controlled by endog...
journal_title:Genes & development
pub_type: 杂志文章
doi:
更新日期:2000-05-01 00:00:00
abstract::The repression of the maternally inherited Igf2 allele has been proposed to depend on a methylation-sensitive chromatin insulator organized by the 11 zinc finger protein CTCF at the H19 imprinting control region (ICR). Here we document that point mutations of the nucleotides in physical contact with CTCF within the en...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.254903
更新日期:2003-03-01 00:00:00
abstract::The ubiquitin-specific protease (USP) family is the largest group of cysteine proteases. Cancer genomic analysis identified frequent amplification of USP21 (22%) in human pancreatic ductal adenocarcinoma (PDAC). USP21 overexpression correlates with human PDAC progression, and enforced expression of USP21 accelerates m...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.326314.119
更新日期:2019-10-01 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
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journal_title:Genes & development
pub_type: 杂志文章
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更新日期:1989-05-01 00:00:00