Abstract:
:Ras-genes encode for proteins important for transmitting extracellular signals from the cytoplasm to the nucleus. In this study we investigated the impact of Ras on cell cycle progression after hepatectomy by using adenoviral vectors (adv) expressing beta-galactosidase (beta-gal), a dominant-negative (Ras N17) or a dominant-active (Ras 61L) form of H-Ras. Partial hepatectomy was performed in mice treated with the different adenoviruses and cell cycle progression was studied by analysing factors involved in cell cycle control during liver regeneration. After hepatectomy, adv Ras 61L increases DNA synthesis significantly in comparison to the other treatment groups. Higher Ras activity results in an early increase of transcriptional active E2F-3, which is associated with higher cyclin E, but almost unchanged cyclin D protein expression. However, Northern blot analysis and cyclin E promoter experiments indicate that, besides transcriptional mechanisms also post-transcriptional mechanisms are involved in regulating cyclin E protein expression after partial hepatectomy in mice treated with adv Ras 61L. Cyclin E phosphorylation studies demonstrate that adv Ras 61L results in hypophosphorylation of cyclin E compared to the control group at early time points after hepatectomy, when cyclin E protein expression strongly increases and there is only a minor effect on cyclin E mRNA levels. Our experiments indicate adv Ras 61L in vivo increases Cyclin E expression by higher transcription via E2F and a post-transcriptional mechanism. These mechanisms result in an earlier activation of an active CDK2/Cyclin E complex which, in turn, triggers DNA synthesis.
journal_name
Oncogenejournal_title
Oncogeneauthors
Lüdde T,Kubicka S,Plümpe J,Liedtke C,Manns MP,Trautwein Cdoi
10.1038/sj.onc.1204690subject
Has Abstractpub_date
2001-08-30 00:00:00pages
5264-78issue
38eissn
0950-9232issn
1476-5594journal_volume
20pub_type
杂志文章相关文献
ONCOGENE文献大全abstract::The release of cytochrome c from the intermembrane space of mitochondria into the cytosol is one of the critical events in apoptotic cell death. In the present study, it is shown that release of cytochrome c and apoptosis induced by tumor necrosis factor alpha (TNF) in HeLa cells can be inhibited by (i) overexpression...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1206053
更新日期:2002-11-21 00:00:00
abstract::The A-myb gene belongs to the family of the c-myb proto-oncogene. We report here the cloning from a B lymphocyte cDNA library of the previously missing 3' half of the human A-myb cDNA, thus closing the previously still incomplete open reading frame. Analysis of the homologies between the different myb proteins reveals...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1994-09-01 00:00:00
abstract::A dual role of transforming growth factor β (TGF-β), to both suppress and promote tumor progression and metastasis, has been well established, but its molecular basis has remained elusive. In this review, we focus on Smad proteins, which are central mediators of the signal transduction of TGF-β family members. We desc...
journal_title:Oncogene
pub_type: 杂志文章,评审
doi:10.1038/onc.2012.191
更新日期:2013-03-28 00:00:00
abstract::Activation of the TAL1 (or SCL) gene, originally identified through its involvement by a recurrent chromosomal translocation, is the most frequent gain-of-function mutation recognized in T-cell acute lymphoblastic leukemia (T-ALL). The TAL1 proteins contain a basic helix - loop - helix (bHLH) motif characteristic of a...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1202889
更新日期:1999-09-02 00:00:00
abstract::Pilocytic astrocytomas (PAs, WHO grade I) are the most common brain tumors in the pediatric and adolescent population, accounting for approximately one-fifth of central nervous system tumors. Because few consistent molecular alterations have been identified in PAs compared to higher grade gliomas, we performed array c...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2008.110
更新日期:2008-08-07 00:00:00
abstract::Non-small cell lung cancer remains a highly lethal malignancy. Using the tamoxifen inducible Hnf1b:CreERT2 (H) transgenic mouse crossed to the LsL-KrasG12D (K) transgenic mouse, we recently discovered that an Hnf1b positive cell type in the lung is sensitive to adenoma formation when expressing a mutant KrasG12D allel...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/s41388-019-1031-z
更新日期:2020-01-01 00:00:00
abstract::Proteinase-activated receptor 2 (PAR2) is a G protein-coupled receptor that is activated by trypsin-like proteinases. PAR2 is detected in breast tumor specimens; however, it is not clear how PAR2 level in breast cancer cell/tissues compares with normal cell/tissues. Here, we show the elevation of PAR2 protein level in...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2009.163
更新日期:2009-08-27 00:00:00
abstract::Rad54 and Mus81 mammalian proteins physically interact and are important for the homologous recombination DNA repair pathway; however, their functional interactions in vivo are poorly defined. Here, we show that combinatorial loss of Rad54 and Mus81 results in hypersensitivity to DNA-damaging agents, defects on both t...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2016.16
更新日期:2016-09-15 00:00:00
abstract::NUP98 has been involved in multiple recurrent chromosome rearrangements in leukemia. We identified a novel fusion between NUP98 and IQ motif containing G (IQCG) gene from a de novo acute T-lymphoid/myeloid leukemia harboring t(3;11)(q29q13;p15)del(3)(q29). IQCG has two putative coiled-coil domains and one IQ domain. T...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1210999
更新日期:2008-05-29 00:00:00
abstract::An adenovirus mutant lacking the expression of the large E1B protein (DeltaE1B) has been reported to replicate selectively in cells lacking the expression of functionally wild-type (wt) p53. Based on these results the DeltaE1B or ONYX-015 virus has been proposed to be an oncolytic virus which might be useful to treat ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1202886
更新日期:1999-09-09 00:00:00
abstract::Protein kinase CK2 is a ubiquitous and pleiotropic Ser/Thr protein kinase involved in cell growth and transformation. Here we report the identification by yeast interaction trap of a CK2 interacting protein, UBC3B, which is highly homologous to the E2 ubiquitin conjugating enzyme UBC3/CDC34. UBC3B complements the yeas...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1205574
更新日期:2002-06-06 00:00:00
abstract::Chk1 is a serine/threonine protein kinase that is activated by a wide range of DNA-damaging agents to slow the cell cycle during S phase and G2/M. Abrogation of these cell-cycle checkpoints using Chk1 inhibitors results in hypersensitivity to DNA-damaging agents in vitro and may provide a potential therapeutic tool to...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2008.482
更新日期:2009-03-19 00:00:00
abstract::Rho GTPases are critical signal transducers of multiple pathways. They have been proposed to be useful anti-neoplastic targets for over two decades, especially in Ras-driven cancers. Until recently, however, few in vivo studies had been carried out to test this premise. Several recent mouse model studies have verified...
journal_title:Oncogene
pub_type: 杂志文章,评审
doi:10.1038/onc.2016.473
更新日期:2017-06-08 00:00:00
abstract::Malignant peripheral nerve sheath tumors (MPNSTs) develop sporadically or in the context of neurofibromatosis type 1. Epidermal growth factor receptor (EGFR) overexpression has been implicated in MPNST formation, but its precise role and relevant signaling pathways remain unknown. We found that EGFR overexpression pro...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2012.579
更新日期:2014-01-09 00:00:00
abstract::Binding partners of the Src homology domains of Vav-1 were characterized by a two-hybrid screening of a Jurkat cell cDNA library. One of the isolated clones encoded a new protein named VIK that belongs to the Kruppel-like zinc-finger gene family. Genome mapping showed that a single gene positioned at chromosome 7q22.1...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1208043
更新日期:2005-01-06 00:00:00
abstract::We have previously determined that the amplified DNA present in the HL60 promyelocytic leukaemia cell line contained 70 kb of continuous DNA sequences around the c-myc gene. In the work presented here we have further defined the HL60 amplicon and find it to be of the order of 160 kb and to contain a large region of DN...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1996-10-03 00:00:00
abstract::We previously reported cell cycle-dependent negative regulation of p185neu (decreased tyrosine phosphorylation and kinase activity, with electrophoretic mobility retarded by serine/threonine phosphorylation) in M phase and the escape of mutation-activated p185neu* from this regulation. Our present results showed that ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1201442
更新日期:1997-11-27 00:00:00
abstract::A lot of attention has been dedicated to investigate the role of the tyrosine kinase receptor MET in tumors. The acquired notion that cancer cells from different histological origin strictly rely on the engagement of this specific oncogene for their growth and survival has certainly justified the development and the u...
journal_title:Oncogene
pub_type: 杂志文章,评审
doi:10.1038/onc.2016.36
更新日期:2016-10-20 00:00:00
abstract::Guanine nucleotide binding protein-like 3-like (GNL3L) is a nucleolar protein and the vertebrate paralogue of nucleostemin (NS). We previously reported that nucleoplasmic mobilization of NS stabilizes MDM2 (mouse double minute 2). Here, we investigated the role of GNL3L as a novel MDM2 regulator. We found that GNL3L b...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2010.550
更新日期:2011-04-07 00:00:00
abstract::Tuberin is the protein product of the tuberous sclerosis-2 (TSC2) gene, which is associated with tuberous sclerosis (TSC), a human genetic syndrome characterized by the development of tumors in a variety of tissues. We have previously shown that tuberin is a widely expressed 180 kDa protein which exhibits specific GTP...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1996-09-05 00:00:00
abstract::Amplification and rearrangements of the epidermal growth factor receptor (EGFR) gene are frequently found in glioblastoma multiforme (GBM). The most common variant is EGFR variant III (EGFRvIII). Research suggests that EGFRvIII could be a marker for a cancer stem cell or tumor-initiating population. If amplification a...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2012.280
更新日期:2013-05-23 00:00:00
abstract::The RAD17 gene product of S. Pombe is an essential component of the checkpoint control pathway which responds to both DNA damage and disruption of replication. We have identified a human cDNA that encodes a polypeptide which is structurally conserved with the S. Pombe Rad17 protein. The human gene, designated hRAD17, ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1202469
更新日期:1999-03-04 00:00:00
abstract::Medulloblastoma (MB) is the most common malignant pediatric brain tumor. Since surviving patients experience severe neurocognitive disabilities, better and more effective treatments are needed to enhance their quality of life. Casein kinase 2 (CK2) is known to regulate cell growth and survival in multiple cancers; how...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/s41388-019-0927-y
更新日期:2019-10-01 00:00:00
abstract::Enhancer of Zeste homologue 2 (EZH2) belongs to the polycomb repressive complex 2 and catalyzes the methylation of histone H3 lysine 27. These pivotal epigenetic marks are altered in many cancers, including melanoma, as a result of EZH2 overexpression. Here, we show that the non-canonical-NF-kB pathway accounts for mo...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2015.331
更新日期:2016-05-01 00:00:00
abstract::The p53 tumor suppressor protein plays a central role in maintaining genomic integrity by occupying a nodal point in the DNA damage control pathway. Here it integrates a wide variety of signals, responding in one of several ways, that is, cell cycle arrest, senescence or programmed cell death (apoptosis). Mutations in...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1209952
更新日期:2007-03-08 00:00:00
abstract::MicroRNAs (miRNAs) are small non-coding RNAs involved in the regulation of critical cell processes such as apoptosis, cell proliferation and differentiation. A small set of miRNAs is differentially expressed in hematopoietic cells and seemingly has an important role in granulopoiesis and lineage differentiation. In th...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2009.255
更新日期:2009-11-12 00:00:00
abstract::Cells from patients with the human genetic disorder ataxia-telangiectasia (A-T) are defective in the activation of cell cycle checkpoints in response to ionizing radiation damage. In order to understand the role of ATM in checkpoint control we investigated whether Schizosaccaromyces pombe chk1, a protein kinase implic...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1202257
更新日期:1999-01-07 00:00:00
abstract::Despite extensive characterization of the role of the EWS-ETS fusions, little is known about secondary genetic alterations and their clinical contribution to Ewing sarcoma (ES). It has been demonstrated that the molecular structure of EWS-ETS lacks prognostic value. Moreover, CDKN2A deletion and TP53 mutation, despite...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2011.317
更新日期:2012-03-08 00:00:00
abstract::An essential mode of acquired resistance to radiotherapy (RT) appears to be promotion of tumor cell motility and invasiveness in various cancer types, including glioblastoma, a process resembling 'evasive resistance'. Hence, a logical advancement of RT would be to identify suitable complementary treatment strategies, ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2012.137
更新日期:2013-02-28 00:00:00
abstract::Apoptosis is essential for normal development and maintenance of homeostasis, and disruption of apoptotic pathways is associated with multiple disease states, including cancer. Although initially identified as central regulators of apoptosis at the level of mitochondria, an important role for BCL-2 proteins at the end...
journal_title:Oncogene
pub_type: 杂志文章,评审
doi:10.1038/onc.2008.309
更新日期:2008-10-27 00:00:00