Abstract:
:The phosphatase Cdc25A was shown to be a target of the transcription factor c-Myc. Myc-induced apoptosis appeared dependent on Cdc25A expression and Cdc25A over-expression could substitute for Myc-triggered apoptosis. These findings suggested that an important downstream component of Myc-mediated apoptosis was identified. However and in contrast, we recently reported that during TNFalpha-induced apoptosis, which required c-Myc function, Cdc25A was down-regulated in a human carcinoma cell line. We now provide evidence that Cdc25A rendered the non-transformed rat embryonic cell line 423 refractory to apoptosis, which was induced by serum deprivation and in absence of detectable c-myc levels. The survival promoting activity of cdc25A was abolished upon infection of cells with a full-length cdc25A antisense construct. To identify the signaling proteins mediating the survival function of the phosphatase, cdc25A- and akt- over-expressing pooled clones were exposed to selected chemicals, which inhibit or activate key proteins in signaling pathways. Inhibition of apoptosis by SU4984, NF023 and Rapamycin placed Cdc25A and Akt function downstream of FGF.R, PDGF.R, and compensated G-protein- and PP2A- activity. Interestingly, upon treatment with LY-294002, cdc25A- and akt- over-expressing clones exhibited similar apoptotic patterns as control cells, which indicates that neither Akt- nor Cdc25A-mediated survival functions are dependent on PI.3 kinase activity in rat 423 cells. In cdc25A-overexpressing cells increased levels of serine 473 phosphorylated Akt were found, which co-precipitated with Cdc25A and Raf1. Since activation of proteins requires dephosphorylation of particular residues in addition to site-specific phosphorylation, the anti-apoptotic effect of Cdc25A might derive from its participation in a multimeric protein complex with phosphoAkt and Raf1, two prominent components of survival pathways.
journal_name
Oncogenejournal_title
Oncogeneauthors
Fuhrmann G,Leisser C,Rosenberger G,Grusch M,Huettenbrenner S,Halama T,Mosberger I,Sasgary S,Cerni C,Krupitza Gdoi
10.1038/sj.onc.1204499subject
Has Abstractpub_date
2001-07-27 00:00:00pages
4542-53issue
33eissn
0950-9232issn
1476-5594journal_volume
20pub_type
杂志文章相关文献
ONCOGENE文献大全abstract::Metastatic growth in breast cancer (BC) has been proposed as an exclusive property of cancer stem cells (CSCs). However, formal proof of their identity as cells of origin of recurrences at distant sites and the molecular events that may contribute to tumor cell dissemination and metastasis development are yet to be el...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2014.5
更新日期:2015-02-05 00:00:00
abstract::Cells are under constant attack from genotoxins and rely on a multifaceted DNA damage response (DDR) network to maintain genomic integrity. Central to the DDR are the ATM and ATR kinases, which respond primarily to double-strand DNA breaks (DSBs) and replication stress, respectively. Optimal ATR signaling requires the...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2015.118
更新日期:2016-02-04 00:00:00
abstract::MicroRNAs (miRNAs) make up a novel class of gene regulators; they function as oncogenes or tumor suppressors by targeting tumor-suppressor genes or oncogenes. A recent study that analysed a large number of human cancer cell lines showed that miR-330 is a potential tumor-suppressor gene. However, the function and molec...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2009.192
更新日期:2009-09-24 00:00:00
abstract::Dlk/ZIP kinase is a newly discovered serine/threonine kinase which, due to its homology to DAP kinase, was named DAP like kinase, Dlk. This kinase is tightly associated with nuclear structures, it undergoes extensive autophosphorylation and phosphorylates myosin light chain and core histones H3, H2A and H4 in vitro. M...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1203170
更新日期:1999-12-02 00:00:00
abstract::BRCA1 and BRCA2 are breast cancer susceptibility genes. Mutations within BRCA1 and BRCA1 are responsible for most familial breast cancer cases. Targeted deletion of Brca1 or Brca2 in mice has revealed an essential function for their encoded products, BRCA1 and BRCA2, in cell proliferation during embryogenesis. Mouse m...
journal_title:Oncogene
pub_type: 杂志文章,评审
doi:10.1038/sj.onc.1203968
更新日期:2000-12-11 00:00:00
abstract::Progesterone receptor (PR) is usually co-localized with estrogen receptor (ER) in normal mammary cells. It is not known whether ER/PR-negative human breast cancer arises from an ER/PR-negative cell or from an ER/PR-positive cell that later lost ER/PR. Using intraductal injection of a lentivirus to deliver both an onco...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2015.465
更新日期:2016-08-04 00:00:00
abstract::Polyomavirus infection of adolescent athymic female mice causes a high incidence of mammary adenocarcinomas. We have examined the role of ovarian hormones, age and mammary gland developmental stage at infection on subsequent tumor induction, viral replication and gene expression. Ovariectomy (OVX) of adolescent mice 1...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1995-11-02 00:00:00
abstract::Germline mutations in the p53 tumor suppressor gene are associated with the Li-Fraumeni syndrome, characterized by childhood sarcoma, leukemia and early onset breast cancer and has occasionally been found also in familial breast-ovarian cancer. Most mutations found are of missense type and located in the central regio...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1996-07-18 00:00:00
abstract::Mouse Developmental Kinase 1 (MDK1) is a receptor tyrosine kinase of the eck/eph subfamily expressed in a variety of tissues during early mouse embryogenesis. To obtain further insight into the function of MDK1, we determined identity and localisation of its physiological ligand(s). Staining whole embryos with fusion ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1200800
更新日期:1997-01-09 00:00:00
abstract::Terminal differentiation of skeletal myoblasts is accompanied by down-regulation of vimentin and beta-, gamma-actins and up-regulation of desmin and sarcomeric alpha-actin(s). To investigate whether the normal decline in expression of vimentin and beta-, gamma-actins was coupled to withdrawal of proliferating myoblast...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1989-07-01 00:00:00
abstract::Fanconi anemia is a hereditary cancer susceptibility disorder characterized at the cellular level by spontaneous chromosomal instability and specific hypersensitivity to DNA cross-linking agents such as mitomycin C. This phenotype suggests a possible role for the Fanconi anemia proteins in the repair of DNA lesions in...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1205656
更新日期:2002-07-25 00:00:00
abstract::Germline BAP1 mutations predispose to several cancers, in particular malignant mesothelioma. Mesothelioma is an aggressive malignancy generally associated with professional exposure to asbestos. However, to date, we found that none of the mesothelioma patients carrying germline BAP1 mutations were professionally expos...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2015.243
更新日期:2016-04-14 00:00:00
abstract::Mice transgenic for the leukemia oncogene E2A-PBX1 invariably develop lethal, high-grade T-cell lymphomas by 5 months of age. In this study, retroviral insertional mutagenesis was employed to identify oncogenes that cooperate with the E2A-PBX1 transgene in lymphomagenesis. Neonatal retroviral infection substantially r...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1201670
更新日期:1997-11-27 00:00:00
abstract::The biological outcome of TMPRSS2:ERG chromosomal translocations in prostate cancer (PC) remains poorly understood. To address this, we compared the transcriptional effects of TMPRSS2:ERG expression in a transgenic mouse model with those of ERG knockdown in a TMPRSS2:ERG-positive PC cell line. This reveals that ERG re...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2014.308
更新日期:2015-07-01 00:00:00
abstract::To investigate the relationship between the local configuration of a gene and its level of expression, we constructed a rat cell line, Hy5, carrying a mutant polyomavirus middle T oncogene (pmt) whose overexpression converted the cells to the transformed state. The structure of the transgene was such that pmt was able...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1994-03-01 00:00:00
abstract::MSH2 and MLH1 have a central role in correcting mismatches in DNA occurring during DNA replication and have been implicated in the engagement of apoptosis induced by a number of cytotoxic anticancer agents. The function of MLH1 is not clearly defined, although it is required for mismatch repair (MMR) and engagement of...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1206252
更新日期:2003-02-13 00:00:00
abstract::DAL-1 (differentially expressed in adenocarcinoma of the lung)/4.1B is a tumor suppressor gene on human chromosome 18p11.3 whose expression is lost in >50% of primary non-small-cell lung carcinomas. Based on sequence similarity, DAL-1/4.1B has been assigned to the Protein 4.1 superfamily whose members interact with pl...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1208057
更新日期:2004-10-14 00:00:00
abstract::Normal function of the p53 gene is integral to the cellular response to genotoxic stress. One prediction arising from this is that p53 deficiency results in an increased mutation frequency. However, limited evidence has been produced in support of this idea. In order to further investigate the in vivo role of p53 in s...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1201040
更新日期:1997-05-01 00:00:00
abstract::Individuals affected with the Gorlin syndrome inherit a germ-line mutation of the patched (Ptc1) developmental gene and, analogously to Ptc1 heterozygous mice, show an increased susceptibility to spontaneous tumor development. Human and mouse Ptc1 heterozygotes (Ptc1(+/-)) are also hypersensitive to ionizing radiation...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1205973
更新日期:2002-10-24 00:00:00
abstract::Guanine nucleotide exchange factors from the Dbl family are proto-oncogenic proteins that activate small GTPases of the Rho family. Here we report the characterization of GEF720, a novel Dbl-like protein related to p115Rho-GEF. GEF720 activated RhoA both in our recently developed Yeast Exchange Assay and in biochemica...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1204921
更新日期:2001-11-01 00:00:00
abstract::In a large proportion of familial and sporadic cases of Hirschsprung disease (HSCR) mutations in the RET (rearranged during transfection) protooncogene have been described. We have investigated the structure of the RET gene promoter and have analysed a region of approximately 1000 nucleotides in its promoter and 5'-up...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1202165
更新日期:1998-11-19 00:00:00
abstract::tal-1 deletions are caused by a site specific recombination, which exclusively occurs in 12-26% of T-cell acute lymphoblastic leukemias (T-ALL). In a previous study on a large series of T-ALL we demonstrated an apparent preferential occurrence of tal-1 deletions in CD3- and CD3+ alpha beta lineage T-ALL with TcR-delta...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1994-07-01 00:00:00
abstract::Poly(ADP-ribose) polymerase 1 (PARP1) is a DNA damage sensor, which upon activation, recruits downstream proteins by poly(ADP-ribosyl)ation (PARylation). However, it remains largely unclear how PARP1 activity is regulated. Interestingly, the data obtained through this study revealed that PARP1 was co-immunoprecipitate...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/s41388-018-0506-7
更新日期:2019-02-01 00:00:00
abstract::Tbx3 is a member of the T-box family of transcription factors. Mutations in Tbx3 cause ulnar-mammary syndrome, an autosomal dominant disorder characterized by upper limb defects, apocrine-gland defects including mammary hypoplasia, and tooth, hair and genital defects. In cell culture, Tbx3 and its close relative Tbx2 ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1205476
更新日期:2002-05-30 00:00:00
abstract::The balance between acetylation and deacetylation of histone and nonhistone proteins controls gene expression in a variety of cellular processes, with transcription being activated by acetyltransferases and silenced by deacetylases. We report here the formation and enzymatic characterization of a complex between the a...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1207327
更新日期:2004-03-18 00:00:00
abstract::The chicken c-ets-1 locus encodes two transcription factors, p54c-ets-1 and p68c-ets-1 that differ in their N-termini, encoded respectively by the I54 and alpha beta exons. p68c-ets-1 equivalents are only found in birds and reptiles while p54c-ets-1 is widely conserved in vertebrates, from amphibians to mammals. Thus,...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1994-11-01 00:00:00
abstract::Urothelial carcinoma (UC) carcinogenesis has been hypothesized to occur through epigenetic repression of tumor-suppressor genes (TSGs). By quantitative real-time polymerase chain reaction array, we found that one potential TSG, angiopoietin-like 4 (ANGPTL4), was expressed at very low levels in all bladder cancer cell ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2017.375
更新日期:2018-02-01 00:00:00
abstract::Homozygous mutations of the recessive oncogene lethal-(2) giant larvae (l(2)gl) of Drosophila melanogaster cause lethal neoplasms of the imaginal discs and the brain hemisphere. A 13-kb DNA segment spanning the l(2)gl+ locus has been inserted into P element vectors and used for P-mediated transformation. The P-l(2)gl+...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1987-05-01 00:00:00
abstract::Although cell invasion is a necessary early step in cancer metastasis, its regulation is not well understood. We have previously shown, in human prostate cancer, that transforming growth factor beta (TGFbeta)-mediated increases in cell invasion are dependent upon activation of the serine/threonine kinase, p38 MAP kina...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1209337
更新日期:2006-05-18 00:00:00
abstract::Members of the src family of tyrosine kinases are composed of amino acid sequences which can be divided into three regions: the unique amino-terminal 80 residues; the next 180 residues of conserved but non-catalytic sequence; and the catalytic carboxy-terminal half of the molecule. To characterize the elements that re...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1992-02-01 00:00:00