Abstract:
:ErbB4, a member of the epidermal growth factor receptor family, plays a role in normal breast and breast cancer development by regulating mammary epithelial cell proliferation, survival and differentiation. In this study, we show that WWP1, a C2-WW-HECT type E3 ubiquitin ligase, binds, ubiquitinates and destructs ErbB4-CYT1, but much less efficiently for CYT2, isoforms (both JMa and JMb). The protein-protein interaction occurs primarily between the first and third WW domains of WWP1 and the second PY motif of ErbB4. Knockdown of WWP1 by two different small interfering RNAs increases the endogenous ErbB4 protein levels in both MCF7 and T47D breast cancer cell lines. In addition, overexpression of the wild type, but not the catalytic inactive WWP1, dramatically decreases the endogenous ErbB4 protein levels in MCF7. Importantly, we found that WWP1 negatively regulates the heregulin-beta1-stimulated ErbB4 activity as measured by the serum response element report assay and the BRCA1 mRNA expression. After a systematic screening of all WWP1 family members by small interfering RNA, we found that AIP4/Itch and HECW1/NEDL1 also negatively regulate the ErbB4 protein expression in T47D. Interestingly, the protein expression levels of both WWP1 and ErbB4 are higher in estrogen receptor-alpha-positive than in estrogen receptor-alpha-negative breast cancer cell lines. These data suggest that WWP1 and its family members suppress the ErbB4 expression and function in breast cancer.
journal_name
Oncogenejournal_title
Oncogeneauthors
Li Y,Zhou Z,Alimandi M,Chen Cdoi
10.1038/onc.2009.162subject
Has Abstractpub_date
2009-08-20 00:00:00pages
2948-58issue
33eissn
0950-9232issn
1476-5594pii
onc2009162journal_volume
28pub_type
杂志文章相关文献
ONCOGENE文献大全abstract::There is a large body of evidence suggesting the connexin gap junction proteins appear to act as tumor suppressors, and their tumor inhibitory effect is usually attributed to their main function of cell coupling through gap junctions. However, some cancer cells (e.g. the rat bladder carcinoma BC31 cell line) are cell-...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1203340
更新日期:2000-01-27 00:00:00
abstract::Bracken fern is the environmental co-carcinogen of BPV-4 in the induction of neoplasias of the upper alimentary canal of cattle. The flavonoid quercetin is one of the most potent and best characterised mutagens present in the fern. We have shown that transfection with BPV-4 DNA and exposure to a single dose of quercet...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1201796
更新日期:1998-05-28 00:00:00
abstract::Many lines of evidence indicate that connexin genes expressing gap junction (GJ) proteins inhibit tumor cell proliferation. However, the precise molecular mechanisms remain unclear. In this study, we show that overexpression of connexin43 (Cx43) suppressed proliferation of human osteosarcoma U2OS cells through inhibit...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1204563
更新日期:2001-07-12 00:00:00
abstract::Beta-transducin repeats-containing proteins (beta-TrCP) serve as the substrate recognition subunits for the SCFbeta-TrCP E3 ubiquitin ligases. These ligases ubiquitinate specifically phosphorylated substrates and play a pivotal role in the regulation of cell division and various signal transduction pathways, which, in...
journal_title:Oncogene
pub_type: 杂志文章,评审
doi:10.1038/sj.onc.1207389
更新日期:2004-03-15 00:00:00
abstract::The gene for von Recklinghausen neurofibromatosis type 1 (NF1) was recently identified by positional cloning and found to encode a protein with sequence similarity to a family of eucaryotic GTPase-activating proteins (GAPs). Expression of the NF1-GAP-related domain (NF1GRD) has been shown to complement yeast strains d...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1993-03-01 00:00:00
abstract::Genetic and biochemical evidence suggest that conserved region 3 (CR3) of the adenovirus Ela polypeptide can provide two distinct and separable functions: an N-terminal transcriptional activation region and a C-terminal promoter targeting region. It is thought that the promoter targeting region of Ela CR3 interacts wi...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1994-12-01 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::Mutations in p53 change the sensitivity to cancer chemotherapeutic drugs. Whereas many drugs, including the vinca alkaloids, often become less effective when p53 is transcriptionally inactivated, several, most notably paclitaxel, may become more effective. In studying the underlying mechanism(s), we found that increas...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1201658
更新日期:1998-03-26 00:00:00
abstract::The Epstein-Barr virus latency-associated membrane protein LMP2A has been shown to activate the survival kinase Akt in epithelial and B cells in a phosphoinositide 3-kinase-dependent fashion. In this study, we demonstrate that the signalling scaffold Shb associates through SH2 and PTB domain interactions with phosphor...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1210298
更新日期:2007-07-26 00:00:00
abstract::Malignant mesotheliomas (MMs) are very aggressive tumors that respond poorly to standard chemotherapeutic approaches. The phosphatidylinositol 3-kinase (PI3K)/AKT pathway has been implicated in tumor aggressiveness, in part by mediating cell survival and reducing sensitivity to chemotherapy. Using antibodies recognizi...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1208744
更新日期:2005-09-08 00:00:00
abstract::Imatinib-acquired resistance related to the presence of secondary point mutations has become a frequent event in gastrointestinal stromal tumors. Here, transient transfection experiments with plasmids carrying two different KIT-acquired point mutations were performed along with immunoprecipitation of total protein ext...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1209639
更新日期:2006-10-05 00:00:00
abstract::The eph gene encodes a putative receptor tyrosine kinase for an as yet unknown ligand. Some human cancer cells have been found to overexpress eph mRNAs without gene amplification. We show here that NIH3T3 cells acquire tumorigenic ability in nude mice and make colonies in soft agar with a viral LTR (Long Terminal Repe...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1990-03-01 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::Exposure of CV-1P cells to hypoxic conditions results in reversible cell cycle arrest concomitant with accumulation of pRB in the hypophosphorylated, growth suppressive form. Similar to cell cycle arrest induced by serum starvation, we show here that hypoxia-induced arrest is accompanied by a decrease in pRB-directed ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1202159
更新日期:1998-11-05 00:00:00
abstract::CD97, a member of the adhesion family of G-protein-coupled receptors (GPCRs), complexes with and potentiates lysophosphatidic acid (LPA) receptor signaling to the downstream effector RHOA. We show here that CD97 was expressed in a majority of thyroid cancers but not normal thyroid epithelium and that the level of CD97...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2012.301
更新日期:2013-05-30 00:00:00
abstract::The function of Bcl-2 family members on the endoplasmic reticulum has received increasing attention in recent years. The endoplasmic reticulum is the major organelle involved in intracellular calcium homeostasis and calcium signaling, including calcium signals that mediate apoptosis induction by anticancer drugs. But ...
journal_title:Oncogene
pub_type: 杂志文章,评审
doi:10.1038/sj.onc.1207519
更新日期:2004-04-12 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::Cyclooxygenase (COX)-2 is upregulated in hepatocellular carcinoma (HCC). However, the direct causative effect of COX-2 in spontaneous HCC formation remains unknown. We thus investigate the role and molecular pathogenesis of COX-2 in HCC by using liver-specific COX-2 transgenic (TG) mice. We found spontaneous HCC forma...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2017.73
更新日期:2017-08-01 00:00:00
abstract::Treatment of mouse (12)1/CA cells with adriamycin or irradiation with U.V.C. induces p53-dependent transcription of a beta-galactosidase reporter and the endogenous p21/Waf1/Cip1 gene. Despite the induction of Waf1, the cells arrest only transiently in G1 or G2, then resume growth and eventually undergo apoptosis. In ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1201104
更新日期:1997-05-29 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::There is now much evidence to suggest that the p53 tumour suppressor protein functions to monitor the integrity of the genome. When DNA damage is detected, p53 suppresses cell growth to allow repair or directs the cell into apoptosis. The mechanism of action of p53 is as yet unclear but recent evidence has accumulated...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1995-10-05 00:00:00
abstract::Epithelial-to-mesenchymal transition (EMT) promotes cell motility, which is important for the metastasis of malignant cells, and blocks CD95-mediated apoptotic signaling triggered by immune cells and chemotherapeutic regimens. CD95L, the cognate ligand of CD95, can be cleaved by metalloproteases and released as a solu...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2014.55
更新日期:2015-02-19 00:00:00
abstract::Murine radiation-induced acute myeloid leukaemia (AML) is characterized by loss of one copy of chromosome 2. Previously, we positioned the critical haematopoietic-specific transcription factor PU.1 within a minimally deleted region. We now report a high frequency (>65%) of missense mutation at codon 235 in the DNA-bin...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1208422
更新日期:2005-05-19 00:00:00
abstract::We report here the nucleic acid sequence and deduced amino acid sequence of a cDNA for TIS7, a gene induced by mitogens in 3T3 cells and by nerve growth factor in PC12 pheochromocytoma cells. A fragment of the TIS7 gene has previously been cloned from murine fibroblast cells infected with Newcastle Disease Virus. The ...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1989-10-01 00:00:00
abstract::The intrinsic mitochondrial apoptotic pathway acts through two core pro-apoptotic proteins Bax (Bcl2-associated X protein) and Bak (Bcl2-antagonist/killer 1). Although Bax and Bak seem to have redundant roles in apoptosis, accumulating evidence also suggests that they might not be interchangeable under certain conditi...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2011.497
更新日期:2012-06-28 00:00:00
abstract::A better understanding of the link between cellular metabolism and tumorigenesis is needed. Here, we report characterization of a novel protein named coiled-coil helix tumor and metabolism 1 (CHTM1). We have found that CHTM1 is associated with cancer and cellular metabolism. CHTM1 localizes to mitochondria and cytosol...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/s41388-017-0051-9
更新日期:2018-04-01 00:00:00
abstract::Most cases of breast cancer (BrCa) mortality are due to vascular metastasis. BrCa cells must intravasate through endothelial cells (ECs) to enter a blood vessel in the primary tumor and then adhere to ECs and extravasate at the metastatic site. In this study we demonstrate that inhibition of hypoxia-inducible factor (...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2011.365
更新日期:2012-04-05 00:00:00
abstract::SMARCB1 (Snf5/Ini1/Baf47) is a potent tumor suppressor, the loss of which serves as the diagnostic feature in malignant rhabdoid tumors (MRT) and atypical teratoid/rhabdoid tumors (AT/RT), two highly aggressive forms of pediatric neoplasms. SMARCB1 is a core subunit of Swi/Snf chromatin remodeling complexes, and loss ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2013.261
更新日期:2014-06-05 00:00:00
abstract::Unique hybrids (HINS and CANS lines) between macrophages and a myeloma cell line, NS1 initially expressed myeloma functions but later expressed active macrophage functions together with constitutive expression of c-fos gene. Enhancement of c-fos transcription was also observed in activated mouse peritoneal macrophages...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1988-05-01 00:00:00
abstract::The Mucin 1 (MUC1) protein is overexpressed in various cancers and mediates chemotherapy resistance. However, the mechanism is not fully understood. Given that most chemotherapeutic drugs disrupt ER homeostasis as part of their toxicity, and MUC1 expression is regulated by proteins involved in ER homeostasis, we inves...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/s41388-020-1225-4
更新日期:2020-04-01 00:00:00