Abstract:
:The diverse checkpoint responses to DNA damage may reflect differential sensitivities by molecular components of the damage-signalling network to the type and amount of lesions. Here, we determined the kinetics of activation of the checkpoint kinases ATM and Chk2 (the latter substrate of ATM) in relation to the initial yield of genomic DNA single-strand (SSBs) and double-strand breaks (DSBs). We show that doses of gamma-radiation (IR) as low as 0.25 Gy, which generate vast numbers of SSBs but only a few DSBs per cell (<8), promptly activate ATM kinase and induce the phosphorylation of the ATM substrates p53-Ser15, Nbs1-Ser343 and Chk2-Thr68. The full activation of Chk2 kinase, however, is triggered by treatments inflicting >19 DSBs per cell (e.g. 1 Gy), which cause Chk2 autophosphorylation on Thr387, Chk2-dependent accumulation of p21waf1 and checkpoint arrest in the S phase. Our results indicate that, in contrast to ATM, Chk2 activity is triggered by a greater number of DSBs, implying that, below a certain threshold level of lesions (<19 DSBs), DNA repair can occur through ATM, without enforcing Chk2-dependent checkpoints.
journal_name
Oncogenejournal_title
Oncogeneauthors
Buscemi G,Perego P,Carenini N,Nakanishi M,Chessa L,Chen J,Khanna K,Delia Ddoi
10.1038/sj.onc.1207986subject
Has Abstractpub_date
2004-10-07 00:00:00pages
7691-700issue
46eissn
0950-9232issn
1476-5594pii
1207986journal_volume
23pub_type
杂志文章相关文献
ONCOGENE文献大全abstract::Cbl proteins are ubiquitin protein ligases, which ubiquitinate activated tyrosine kinases and target them for degradation. Both c-Cbl and Cbl-b have an ubiquitin associated (UBA) domain at their C-terminal end. We observed that high molecular weight ubiquitinated proteins constitutively coimmunoprecipitated with trans...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1207952
更新日期:2004-09-16 00:00:00
abstract::Abundant data support a key role for the transcription factor nuclear factor-kappaB (NF-kappaB) signaling pathway in controlling the initiation and progression of human cancer. NF-kappaB and associated regulatory proteins such as IkappaB kinase (IKK) are activated downstream of many oncoproteins and there is much evid...
journal_title:Oncogene
pub_type: 杂志文章,评审
doi:10.1038/sj.onc.1209942
更新日期:2006-10-30 00:00:00
abstract::Cancer cells harboring oncogenic BRaf mutants, but not oncogenic KRas mutants, are sensitive to MEK inhibitors (MEKi). The mechanism underlying the intrinsic resistance to MEKi in KRas-mutant cells is under intensive investigation. Here, we pursued this mechanism by live imaging of extracellular signal-regulated kinas...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2015.16
更新日期:2015-11-05 00:00:00
abstract::The most ominous development in tumor progression is the transition to an invasive and metastatic phenotype. Little is known, however, about the molecular alterations that cause a tumor to become invasive. In view of this, we have used microarray expression analysis to evaluate the expression profiles of a unique pane...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1204379
更新日期:2001-05-17 00:00:00
abstract::In many differentiating cells, a reduction of c-myc proto-oncogene expression is a prerequisite for terminal differentiation. The downmodulation of c-myc in differentiating cells is due to at least two different mechanisms: (i) an elongation block to c-myc transcription activated during an early phase of differentiati...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1993-08-01 00:00:00
abstract::Prostate tumors develop resistance to androgen deprivation therapy (ADT) by multiple mechanisms, one of which is to express constitutively active androgen receptor (AR) splice variants lacking the ligand-binding domain. AR splice variant 7 (AR-V7, also termed AR3) is the most abundantly expressed variant that drives p...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2013.284
更新日期:2014-06-12 00:00:00
abstract::Ewing sarcoma is characterized by the expression of the chimeric EWSR1-FLI1 transcription factor. Proteomic analyses indicate that the decrease of EWSR1-FLI1 expression leads to major changes in effectors of the dynamics of the actin cytoskeleton and the adhesion processes with a shift from cell-to-cell to cell-matrix...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2016.498
更新日期:2017-06-22 00:00:00
abstract::Persistent activation of the Abl tyrosine kinase in the BCR-ABL fusion protein is the major cause of chronic myeloid leukemia (CML). Among many other substrates BCR-ABL phosphorylates STAT5 and Src family kinases (SFK). Activated pSTAT5 is essential for initial transformation and maintenance of the disease. Cytokine-i...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2012.369
更新日期:2013-08-01 00:00:00
abstract::Anaplastic lymphoma kinase (ALK) is a transmembrane receptor tyrosine kinase in the insulin receptor superfamily. We recently demonstrated that the growth factors pleiotrophin (PTN) and midkine (MK) are ligands for ALK and that upon ALK activation, insulin receptor substrate-1 (IRS-1) and other substrates are phosphor...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1209840
更新日期:2007-02-08 00:00:00
abstract::The VN-11 recombinant retroviruses, originally generated by co-transfection of the avian MH2 and AKRv viral genomes, were molecularly cloned from an infected mouse cell line named N11. The analysis of the proviral genome sequence from one of these recombinants showed a possible envAKR-mycMH2 fusion. Point mutations we...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1994-05-01 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::The Abelson (Abl) family of non-receptor tyrosine kinases has an important role in cell morphogenesis, motility, and proliferation. Although the function of Abl has been extensively studied in leukemia, its role in epithelial cell invasion remains obscure. Using the Drosophila wing epithelium as an in vivo model syste...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2010.155
更新日期:2010-07-15 00:00:00
abstract::Our previous studies suggested that chromosome 8p deletion is associated with metastasis of hepatocellular carcinoma (HCC), in which some novel metastasis suppressor genes might be harbored. The present study aimed to identify the metastatic suppressor gene(s). A cDNA chip was constructed with the expressed sequence t...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1209191
更新日期:2006-03-16 00:00:00
abstract::The ETS transcription factor ERG has been implicated as a major regulator of both normal and aberrant hematopoiesis. In acute myeloid leukemias harboring t(16;21), ERG function is deregulated due to a fusion with FUS/TLS resulting in the expression of a FUS-ERG oncofusion protein. How this oncofusion protein deregulat...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2015.261
更新日期:2016-04-14 00:00:00
abstract::The microenvironment of glioblastoma (GBM) contains high levels of inflammatory cytokine interleukin 6 (IL-6), which contributes to promote tumour progression and invasion. The common epidermal growth factor receptor variant III (EGFRvIII) mutation in GBM is associated with significantly higher levels of IL-6. Further...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2014.225
更新日期:2015-05-28 00:00:00
abstract::Genetic mutations in BRCA1, which is crucial for the process of DNA repair and maintenance of genomic integrity, are known to increase markedly the risk of breast and ovarian cancers. Clinical genetic testing has been used to identify new BRCA1 variants; however, functional assessment and determination of their pathog...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/s41388-019-0968-2
更新日期:2020-01-01 00:00:00
abstract::Accumulating evidences indicate that p120 catenin, a member of the E-cadherin (E-CD)/catenin adhesion complex, plays a role in tumor invasion. To establish the expression pattern of p120 in breast cancer, we analysed 326 breast tissue biopsies by tissue microarray. Most of the lobular tumors (88%) showed exclusive cyt...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1207439
更新日期:2004-04-22 00:00:00
abstract::Acute promyelocytic leukemia (APL) is characterized by the expansion of malignant myeloid cells blocked at the promyelocytic stage of hemopoietic development, and is associated with reciprocal chromosomal translocations always involving the retinoic acid receptor alpha (RARalpha) gene on chromosome 17. As a consequenc...
journal_title:Oncogene
pub_type: 杂志文章,评审
doi:10.1038/sj.onc.1203088
更新日期:1999-09-20 00:00:00
abstract::Histone modifications such as acetylation, methylation and phosphorylation have been implicated in fundamental cellular processes such as epigenetic regulation of gene expression, organization of chromatin structure, chromosome segregation, DNA replication and DNA repair. Males absent on the first (MOF) is responsible...
journal_title:Oncogene
pub_type: 杂志文章,评审
doi:10.1038/sj.onc.1210607
更新日期:2007-08-13 00:00:00
abstract::Silencing of the MLH1 gene by promoter hypermethylation is the mechanism underlying the microsatellite instability (MSI) phenotype in endometrial cancers. However, the profile of CpG methylation in a wide range of MLH1 promoters in endometrial cancers and in the normal endometrium is largely unknown. The present study...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1206365
更新日期:2003-04-17 00:00:00
abstract::Cell cycle checkpoints ensure genome integrity and are frequently compromised in human cancers. A therapeutic strategy being explored takes advantage of checkpoint defects in p53-deficient tumors in order to sensitize them to DNA-damaging agents by eliminating Chk1-mediated checkpoint responses. Using mouse models, we...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2012.84
更新日期:2013-01-31 00:00:00
abstract::The retinoblastoma protein (pRB) has the dual capability to negatively regulate both E2F-induced cell cycle entry and E2F1-induced apoptosis. In this report, we characterize a unique pRB-E2F1 interaction. Using mutagenesis to disrupt E2F1 binding, we find that the ability of pRB to regulate E2F1-induced apoptosis is d...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1210803
更新日期:2008-03-06 00:00:00
abstract::Hepatocellular carcinoma (HCC) is the fifth leading cause of cancer-related mortality in the United States. Exploring the mechanism of HCC and identifying ideal targets is critical. In the present study, we demonstrated metabolism dysfunction might be a key diver for the development of HCC. The mitochondrial amidoxime...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/s41388-020-01417-6
更新日期:2020-09-01 00:00:00
abstract::rho genes have been found in both lower and higher eucaryotes. They code for proteins of 21 kDa, highly conserved in evolution, which belong to the superfamily of ras GTPases. Among the members of this superfamily there are proteins with a regulatory function, such as ras, and proteins involved in vesicular traffickin...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1993-05-01 00:00:00
abstract::Neuroblastoma is the second most common pediatric malignancy, characterized by a high rate of unexplained spontaneous remissions. Much progress has been made in understanding neuroblastoma differentiation triggered by certain agents such as retinoic acid. However, little is known about the signalling pathways that lea...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1208494
更新日期:2005-05-05 00:00:00
abstract::Heat shock protein 110 (HSP110) is induced by different stresses and, through its anti-apoptotic and chaperoning properties, helps cells survive these adverse situations. In colon cancers, HSP110 is abnormally abundant. We have recently shown that colorectal cancer patients with microsatellite instability (MSI) had an...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2016.403
更新日期:2017-04-20 00:00:00
abstract::The p53 tumor suppressor protein is frequently mutated in human tumors. It is thought that the p53 pathway is indirectly impaired in the remaining tumors, for example by overexpression of its important regulators Mdm2 and Mdm4, making them attractive targets for the development of anti-cancer agents. Recent studies ha...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2009.522
更新日期:2010-04-22 00:00:00
abstract::Cancer development results from deregulated control of stem cell populations and alterations in their surrounding environment. Notch signaling is an important form of direct cell-cell communication involved in cell fate determination, stem cell potential and lineage commitment. The biological function of this pathway ...
journal_title:Oncogene
pub_type: 杂志文章,评审
doi:10.1038/onc.2008.225
更新日期:2008-09-01 00:00:00
abstract::The REL gene is amplified in many human B-cell lymphomas and we have previously shown that expression of REL from a retroviral vector can malignantly transform chicken spleen cells in vitro. To identify REL protein functions necessary for malignant transformation, we have performed deletion analysis on REL sequences e...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1206801
更新日期:2003-10-09 00:00:00
abstract::Recent evidence has implicated the transmembrane co-receptor neuropilin-1 (NRP1) in cancer progression. Primarily known as a regulator of neuronal guidance and angiogenesis, NRP1 is also expressed in multiple human malignancies, where it promotes tumor angiogenesis. However, non-angiogenic roles of NRP1 in tumor progr...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2016.482
更新日期:2017-06-15 00:00:00