Abstract:
:The role of cbl-b in signaling by the epidermal growth factor receptor (EGFR) was studied and compared with c-cbl. We demonstrate in vivo, that cbl-b, like c-cbl, is phosphorylated and recruited to the EGFR upon EGF stimulation and both cbl proteins can bind to the Grb2 adaptor protein. To investigate the functional role of cbl proteins in EGFR signaling, we transfected cbl-b or c-cbl into 32D cells overexpressing the EGFR (32D/EGFR). This cell line is absolutely dependent on exogenous IL-3 or EGF for sustained growth. 32D/EGFR cells overexpressing cbl-b showed markedly inhibited growth in EGF compared to c-cbl transfectants and vector controls. This growth inhibition by cbl-b was the result of a dramatic increase in the number of cells undergoing apoptosis. Consistent with this finding, cbl-b overexpression markedly decreased the amplitude and duration of AKT activation upon EGF stimulation compared to either vector controls or c-cbl overexpressing cells. In addition, the duration of EGF mediated MAP kinase and Jun kinase activation in cells overexpressing cbl-b is shortened. These data demonstrate that cbl-b inhibits EGF-induced cell growth and that cbl-b and c-cbl have distinct roles in EGF mediated signaling.
journal_name
Oncogenejournal_title
Oncogeneauthors
Ettenberg SA,Keane MM,Nau MM,Frankel M,Wang LM,Pierce JH,Lipkowitz Sdoi
10.1038/sj.onc.1202499subject
Has Abstractpub_date
1999-03-11 00:00:00pages
1855-66issue
10eissn
0950-9232issn
1476-5594journal_volume
18pub_type
杂志文章相关文献
ONCOGENE文献大全abstract::Transcription from the rat transforming growth factor alpha (TGF-alpha) promoter initiates at multiple sites within a 200-bp G+C-rich region that lacks TATA and CAAT motifs but contains multiple potential binding sites for the transcription factor Sp1. In the present study, we used deletion analysis to establish the 5...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1992-09-01 00:00:00
abstract::Atypical protein kinase C (aPKC) and Lethal giant larvae (Lgl) regulate apical-basal polarity in Drosophila and mammalian epithelia. At the apical domain, aPKC phosphorylates and displaces Lgl that, in turn, maintains aPKC inactive at the basolateral region. The mutual exclusion of these two proteins seems to be cruci...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1210389
更新日期:2007-08-30 00:00:00
abstract::p27Kip1 plays an important role in cell cycle progression by negatively regulating the activity of cyclin-Cdk complexes. To understand how p27Kip1 functions, the level and subcellular location of p27Kip1 in Swiss/3T3 cells following serum stimulation of quiescent cells was examined. Surprisingly, p27Kip1 was observed ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1202912
更新日期:1999-09-16 00:00:00
abstract::The product of the proto-oncogene fos is a nuclear phosphoprotein. We have investigated if nuclear location of Fos protein is mediated by a nuclear targeting sequence. We show that the cytoplasmic chicken pyruvate kinase protein translocates to the nucleus if fused to the 22 amino acid Fos basic region (amino acids 13...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1991-11-01 00:00:00
abstract::Ferritin is the major intracellular iron storage protein that sequesters excess free iron to minimize generation of iron-catalysed reactive oxygen species. We previously demonstrated that expression of ferritin heavy chain (ferritin H) was induced by pro-oxidants, which is a part of cellular antioxidant response to pr...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1208901
更新日期:2005-11-17 00:00:00
abstract::Frequent allelic losses of chromosome 3p in lung cancer have been reported in a number of studies, and we previously demonstrated that 3p21.3 is one of the common regions of deletion in lung cancers and renal cell carcinomas. To further define a region containing the putative tumor suppressor gene, we performed Southe...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1993-02-01 00:00:00
abstract::Proapoptotic nuclear receptor family member Nur77 translocates from the nucleus to the mitochondria, where it interacts with Bcl-2 to trigger apoptosis. Nur77 translocation is induced by certain apoptotic stimuli, including the synthetic retinoid-related 6-[3-(1-adamantyl)-4-hydroxyphenyl]-2-naphthalenecarboxylic acid...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1209358
更新日期:2006-05-18 00:00:00
abstract::Oncoprotein C-MYC is overexpressed in human metastatic melanomas and melanoma-derived cells where it is required for the suppression of oncogene-induced senescence (OIS). The genetic events that maintain high levels of C-MYC in melanoma cells and their role in OIS are unknown. Here we report that C-MYC in cells from s...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2011.339
更新日期:2012-03-22 00:00:00
abstract::Alternative splicing is a widespread process contributing to structural transcript variation and proteome diversity. In cancer, the splicing process is commonly disrupted, resulting in both functional and non-functional end-products. Cancer-specific splicing events are known to contribute to disease progression; howev...
journal_title:Oncogene
pub_type: 杂志文章,评审
doi:10.1038/onc.2015.318
更新日期:2016-05-12 00:00:00
abstract::As apoptosis defects limit efficacy of anticancer agents, autophagy has been proposed as a novel strategy for radiotherapy enhancement. We previously showed that caspase-3/7 inhibition induces autophagy and promotes radiosensitivity in vitro and in vivo. Therefore, we further investigated the mechanism by which radiat...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2010.74
更新日期:2010-06-03 00:00:00
abstract::Superior cervical ganglia 10 (SCG10), as a microtubule (MT) destabilizer, maintains MT homeostasis and has a critical role in neuronal development, but its function in tumorigenesis has not been characterized. In the present study, we demonstrated that p21-activated kinase 4 (PAK4)-mediated SCG10 phosphorylation regul...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2013.296
更新日期:2014-06-19 00:00:00
abstract::Ras-GRF, a guanine-nucleotide exchange factor that activates Ras p21, was tested for its ability to couple to either tyrosine kinase or heterotrimeric G protein signal transduction pathways. Ras-GRF failed to bind the SH2 and SH3 containing adaptor protein Grb2, either in vitro or in vivo. Furthermore, Ras-GRF did not...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1995-05-18 00:00:00
abstract::Increased cancer stem cell content during development of resistance to tamoxifen in breast cancer is driven by multiple signals, including Sox2-dependent activation of Wnt signalling. Here, we show that Sox2 increases and estrogen reduces the expression of the transcription factor Sox9. Gain and loss of function assay...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/s41388-018-0656-7
更新日期:2019-04-01 00:00:00
abstract::The DNA-binding, transcriptional activation and transforming activities of the Myc protein require dimerization with Max. Max can form also homodimers which are able to bind the same DNA sequence as Myc/Max heterodimers and suppress Myc-induced transcription and transformation. We have recently identified a naturally ...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1995-08-03 00:00:00
abstract::Apoptin, a protein of the chicken anemia virus (CAV), represents a novel potential anticancer therapeutic, because it induces apoptotic death specifically in tumor but not normal cells. The cellular localization appears to be crucial for apoptin's selective toxicity. In normal cells apoptin remains in the cytoplasm, w...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1209923
更新日期:2007-03-08 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::Loss of genetic material, including loss of loci on chromosome arms 6q, 9p, and 10q, occurs frequently in cutaneous melanoma but infrequently in benign melanocytic nevi or other melanocytic lesions, suggesting that these genetic alterations are important in the development and progression of melanoma. To examine wheth...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1200203
更新日期:1998-04-30 00:00:00
abstract::Recognition and elimination of malignant cells by cytotoxic T lymphocytes depends on antigenic peptides generated by proteasomes. It has been established that impairment of the immunoproteasome subunits, that is, PSMB8, PSMB9 and PSMB10 (PSMBs), is critical for malignant cells to escape immune recognition. We report h...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2013.224
更新日期:2014-05-22 00:00:00
abstract::Ras proteins activate Raf and PI-3 kinases, as well as exchange factors for RalA and RalB GTPases. Many previous studies have reported that the Ral-signaling cascade contributes positively to Ras-mediated oncogenesis. Here, using a bioengineered tissue model of early steps in Ras-induced human squamous cell carcinoma ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2009.307
更新日期:2010-01-07 00:00:00
abstract::A proportion of familial breast cancer has recently been shown by genetic linkage analysis to map to chromosome l3q12 (Wooster et al, 1994). This locus contains a tumor suppressor gene BRCA2, mutations in which lead to tumorigenesis. Genetic alterations at this locus have also been shown in pancreatic adenocarcinoma a...
journal_title:Oncogene
pub_type:
doi:
更新日期:1996-07-04 00:00:00
abstract::The gfi-1 gene encodes a zinc finger containing protein that is specifically expressed in T-lymphocytes and is a frequent target of proviral insertion in T-cell lymphoma provoked by infection with MoMuLV--a non acute transforming retrovirus. Expression of a gfi-1 transgene targeted to T-cells by the lck proximal promo...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1202191
更新日期:1998-11-19 00:00:00
abstract::The cellular transcription factor Brn-3a differentially regulates different human papilloma virus (HPV)-16 variants that are associated with different risks of progression to cervical carcinoma in infected humans. The upstream regulatory regions (URRs) of high- and intermediate-risk HPV-16 variants are activated by th...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2010.33
更新日期:2010-05-06 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::We have previously shown (Smith et al., 1994) that antibodies raised against the growth arrest and DNA damage inducible protein Gadd45 co-precipitate proliferating cell nuclear antigen (PCNA), a protein involved in DNA replication and repair. Here we demonstrate that Gadd45 can directly bind to PCNA using a Far-wester...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1995-11-16 00:00:00
abstract::Uracil in DNA results from deamination of cytosine, resulting in mutagenic U : G mispairs, and misincorporation of dUMP, which gives a less harmful U : A pair. At least four different human DNA glycosylases may remove uracil and thus generate an abasic site, which is itself cytotoxic and potentially mutagenic. These e...
journal_title:Oncogene
pub_type: 杂志文章,评审
doi:10.1038/sj.onc.1205996
更新日期:2002-12-16 00:00:00
abstract::Pancreatic ductal adenocarcinoma (PDAC) is a deadly disease and a major health problem in the United States. While the cytokine TGF-β has been implicated in PDAC development, it can exert both pro-tumorigenic and anti-tumorigenic effects that are highly context dependent and incompletely understood. Using three-dimens...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/s41388-018-0264-6
更新日期:2018-08-01 00:00:00
abstract::We have compared the DNase I hypersensitivity of the regulatory region of two estrogen-regulated genes, pS2 and cathepsin D in hormone-dependent and -independent breast carcinoma cell lines. This strategy allowed the identification of two important control regions, one in pS2 and the other in cathepsin D genes. In the...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1202317
更新日期:1999-01-14 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::We isolated three related cDNA clones from a mouse cerebellar library; the type I cDNA was identical to the gene encoding the apoptosis-associated tyrosine kinase (AATYK), whose expression in myeloid precursor cells is increased during growth arrest or apoptosis. Low levels of AATYK mRNA expression were seen in adult ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1204210
更新日期:2001-03-01 00:00:00
abstract::We previously reported that overexpression of the 24 kDa basic fibroblast factor (or FGF-2) isoform provides protection from the cytotoxic effect of ionizing radiation (IR). DNA double-strand breaks (DSB), the IR-induced lethal lesions, are mainly repaired in human cells by non-homologous end joining system (NHEJ). NH...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1205838
更新日期:2002-09-19 00:00:00