Abstract:
:Oncogenesis results from changes in kinetics or in abundance of proteins in signal transduction networks. Recently, it was shown that control of signalling cannot reside in a single gene product, and might well be dispersed over many components. Which of the reactions in these complex networks are most important, and how can the existing molecular information be used to understand why particular genes are oncogenes whereas others are not? We implement a new method to help address such questions. We apply control analysis to a detailed kinetic model of the epidermal growth factor-induced mitogen-activated protein kinase network. We determine the control of each reaction with respect to three biologically relevant characteristics of the output of this network: the amplitude, duration and integrated output of the transient phosphorylation of extracellular signal-regulated kinase (ERK). We confirm that control is distributed, but far from randomly: a small proportion of reactions substantially control signalling. In particular, the activity of Raf is in control of all characteristics of the transient profile of ERK phosphorylation, which may clarify why Raf is an oncogene. Most reactions that really matter for one signalling characteristic are also important for the other characteristics. Our analysis also predicts the effects of mutations and changes in gene expression.
journal_name
Oncogenejournal_title
Oncogeneauthors
Hornberg JJ,Binder B,Bruggeman FJ,Schoeberl B,Heinrich R,Westerhoff HVdoi
10.1038/sj.onc.1208817subject
Has Abstractpub_date
2005-08-25 00:00:00pages
5533-42issue
36eissn
0950-9232issn
1476-5594pii
1208817journal_volume
24pub_type
杂志文章相关文献
ONCOGENE文献大全abstract::During normal tumor growth and in response to some therapies, tumor cells experience acute or chronic deprivation of nutrients and oxygen and induce tumor vascularization. While this occurs predominately through sprouting angiogenesis, tumor cells have also been shown to directly contribute to vessel formation through...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2017.356
更新日期:2018-02-22 00:00:00
abstract::A hallmark of human cancer is heterogeneity, reflecting the complex series of changes resulting in the activation of oncogenes coupled with inactivation of tumor suppressor genes. Breast cancer is no exception and indeed, many studies have revealed considerable complexity and heterogeneity in the population of primary...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2011.433
更新日期:2012-05-17 00:00:00
abstract::TGF-beta/Smads regulate a wide variety of biological responses through transcriptional regulation of target genes. ELF, a beta-spectrin, plays a key role in the transmission of TGF-beta-mediated transcriptional response through Smads. ELF was originally identified as a key protein involved in endodermal stem/progenito...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1208946
更新日期:2005-12-01 00:00:00
abstract::Radiation therapy (RT) is useful for selectively killing cancer cells. However, because high levels of ionizing radiation (IR) are toxic to normal cells, RT cannot be applied repeatedly to cancer patients. Therefore, novel chemicals that enhance the efficacy of chemoradiotherapy (CRT) would be valuable. Here, we repor...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2015.47
更新日期:2015-12-03 00:00:00
abstract::Loss-of-function mutations in the LKB1 (STK11) serine-threonine kinase gene cause Peutz-Jeghers syndrome, which is associated with inherited susceptibility to colorectal and other cancers. No downstream targets of LKB1 kinase activity have been identified. Here we show that LKB1 can direct the phosphorylation of the s...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1206669
更新日期:2003-07-24 00:00:00
abstract::During the evolution into castration or therapy resistance, prostate cancer cells reprogram the androgen responses to cope with the diminishing level of androgens, and undergo metabolic adaption to the nutritionally deprived and hypoxia conditions. AR (androgen receptor) and PKM2 (pyruvate kinase M2) have key roles in...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/s41388-018-0414-x
更新日期:2019-01-01 00:00:00
abstract::Platelet-derived growth factor (PDGF) and vascular endothelial growth factor define a family of dimeric proteins characterized by eight conserved cysteine residues involved in disulfide bonds. Thirteen non-cysteine residues conserved among the platelet-derived/vascular endothelial growth factors were individually muta...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1993-03-01 00:00:00
abstract::Germline mutations in the tumor suppressor BRCA1 predispose women to breast and ovarian cancers. Current evidence demonstrates that mutations in BRCA1 do not directly result in tumor formation, but instead cause genetic instability, subjecting cells to high risks of malignant transformation. In an animal model in whic...
journal_title:Oncogene
pub_type: 杂志文章,评审
doi:10.1038/sj.onc.1203269
更新日期:2000-02-21 00:00:00
abstract::Signals received at the cell surface must be properly transmitted to critical targets within the cell to achieve the appropriate biological response. This process of signal transduction is often initiated by receptor tyrosine kinases (RTKs), which function as entry points for many extracellular cues and play a critica...
journal_title:Oncogene
pub_type: 杂志文章,评审
doi:10.1038/sj.onc.1210394
更新日期:2007-05-14 00:00:00
abstract::Nuclear-targeted high molecular weight 24 kDa fibroblast growth factor 2 (FGF-2) may induce specific cell functions through intracrine mechanisms. The role of nuclear FGF-2 on the metastatic potential of carcinoma cells was examined by conditional FGF-2 expression, which demonstrated that spontaneous metastasis in nud...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1207638
更新日期:2004-06-10 00:00:00
abstract::Lysine methylation of histones and non-histone substrates by the SET domain containing protein lysine methyltransferase (KMT) G9a/EHMT2 governs transcription contributing to apoptosis, aberrant cell growth, and pluripotency. The positioning of chromosomes within the nuclear three-dimensional space involves interaction...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/s41388-019-0723-8
更新日期:2019-05-01 00:00:00
abstract::While screening a chicken kidney cDNA library for the normal homolog of the yes oncogene, we isolated a clone that encodes a novel non-receptor type protein tyrosine kinase of the Src family. We named this gene product Yrk (York), as an acronym for Yes-related kinase. As predicted from the cDNA sequence, the Yrk prote...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1993-04-01 00:00:00
abstract::Akt/PKB is a serine/threonine kinase that promotes tumor cell growth by phosphorylating transcription factors and cell cycle proteins. There is particular interest in finding tumor-specific substrates for Akt to understand how this protein functions in cancer and to provide new avenues for therapeutic targeting. Our l...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1208590
更新日期:2005-06-16 00:00:00
abstract::The initiation, magnitude and duration of an immune response against antigens are a tightly regulated process involving a dynamic, orchestrated balance of pro- and anti-inflammatory pathways in immune cells. Such a delicate balance is critical for allowing efficient immune response against foreign antigens while preve...
journal_title:Oncogene
pub_type: 杂志文章,评审
doi:10.1038/onc.2009.334
更新日期:2010-01-14 00:00:00
abstract::The natural phytoalexin resveratrol (3, 5, 4'-trihydroxystilbene) exhibits both chemopreventive and antitumor activities through a variety of mechanisms. We have shown previously that resveratrol-induced apoptosis of a human colon cancer cell line involved the redistribution of CD95 (Fas/Apo-1) into lipid rafts. Here,...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1208086
更新日期:2004-11-25 00:00:00
abstract::The steady-state levels of p53 mRNA were dramatically lower in immortal chicken embryo fibroblast (CEF) cell lines compared to primary CEF cells. In the presence of cycloheximide (CHX), the steady-state levels of p53 mRNA markedly increased in immortal CEF cell lines, similar to levels found in primary cells. The de n...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1204664
更新日期:2001-08-23 00:00:00
abstract::We evaluated the effect of nitric oxide (NO) on vascular endothelial growth factor (VEGF) gene expression in human A-172 glioblastoma cells and human HepG2 hepatocellular carcinoma cells. The mRNA level of VEGF increased in response to S-Nitroso-N-acetyl-D,L-penicillamine (SNAP) in both cell lines, and increased in mR...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1201201
更新日期:1997-07-24 00:00:00
abstract::The Epstein-Barr virus (EBV) encoded latent membrane protein, LMP1, is oncogenic in rodent fibroblasts and is an essential effector protein in EBV-induced growth-transformation of human B lymphocytes. Previous structure-function studies with LMP1 have relied largely on rodent fibroblast transformation as a functional ...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1995-02-02 00:00:00
abstract::To appreciate the involvement of known or potential susceptibility genes in sporadic breast tumors, we have searched for chromosomal deletions by studying loss of heterozygosity (LOH) at 43 microsatellite (CA)n markers from human chromosomes 10, 11 and 17, in 115 unselected consecutive samples of breast carcinoma with...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1200818
更新日期:1997-01-23 00:00:00
abstract::The expression of normal and mutant ras genes in human acute leukemias was assessed by the direct analysis of p21ras polypeptides, using immunoprecipitation with monoclonal antibodies. High-resolution two-dimensional gel electrophoresis permits the identification of a wide array of activated ras alleles encoding prote...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1987-05-01 00:00:00
abstract::Tuftelin1 (TUFT1), an acidic protein constituent of developing and mineralizing tooth tissues, is regulated by hypoxia and the Hedgehog signaling pathway. We investigated the role of TUFT1 in hepatocellular carcinoma (HCC). qRT-PCR, immunohistochemistry and western blot were employed to evaluate TUFT1 level in HCC. MT...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/s41388-018-0505-8
更新日期:2019-02-01 00:00:00
abstract::Clear cell renal cell carcinoma (ccRCC) is the most common renal cancer and frequently diagnosed at an advanced stage. It is prone to develop unpredictable metastases even with proper treatment. Antiangiogenic therapy is the most effective medical treatment for metastatic ccRCC. Thus, exploration of novel approaches t...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/s41388-020-01428-3
更新日期:2020-09-01 00:00:00
abstract::The transforming potential of adenovirus E1A oncogene products derives largely from the formation of complexes with cellular proteins, including the p105Rb tumor suppressor and a related p107 species, p130 and p300 proteins, and cyclin A (p60cycA). Extensive quantitative analyses using E1A deletion mutants identified ...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1994-02-01 00:00:00
abstract::Tamoxifen (Tam), besides its action as an anti-estrogen, also inhibits cell proliferation of estrogen receptor (ER)-negative cancer cells by an unknown mechanism. In this study, we used ER-negative lung cancer cells to clarify such ER-independent inhibitory effect of Tam. We found that Tam induced G1 growth arrest in ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1202755
更新日期:1999-07-22 00:00:00
abstract::Immunopurified mouse p53 proteins were used to gain experimental access to the mechanisms underlying nonprimate p53 directed suppression of SV40 origin directed DNA replication in vivo. In replication competent HeLa cell extracts containing exogenous T antigen, mouse p53 blocks T antigen dependent DNA synthesis as in ...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1988-10-01 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::Early studies demonstrated that male melanoma patients have worse survival than female patients, yet the detailed mechanisms for this gender difference remain unclear. We analyzed around 100 cases of human melanoma and found that androgen receptor (AR) positive melanoma patients have worse survival outcomes compared w...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2016.330
更新日期:2017-03-23 00:00:00
abstract::Non-small cell lung carcinomas (NSCLCs) are typically resistant against apoptosis induced by standard chemotherapy. We evaluated the effects of the two potential antitumor agents of the lamellarin class on a highly apoptosis-resistant NSCLC cell line. Both the marine alkaloid lamellarin-D and its synthetic amino deriv...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1210833
更新日期:2008-03-27 00:00:00
abstract::Tumor suppressor p53 has been shown to repress expression of vascular endothelial growth factor (VEGF), an endothelial cell-specific mitogen and a key mediator of tumor angiogenesis. The p63 gene, recently identified as a p53-relative, encodes multiple isoforms with structural and functional similarities and differenc...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1205330
更新日期:2002-04-11 00:00:00
abstract::Mitophagy, the selective engulfment and clearance of mitochondria, is essential for the homeostasis of a healthy network of functioning mitochondria and prevents excessive production of cytotoxic reactive oxygen species from damaged mitochondria. The mitochondrially targeted PTEN-induced kinase-1 (PINK1) and the E3 ub...
journal_title:Oncogene
pub_type: 杂志文章,评审
doi:10.1038/onc.2016.302
更新日期:2017-03-01 00:00:00