Abstract:
:The nuclear transport receptor importin-β/karyopherin-β1 is overexpressed in cancers that display genomic instability. It is regarded as a promising cancer target and inhibitors are being developed. In addition to its role in nucleo-cytoplasmic transport, importin-β regulates mitosis, but the programmes and pathways in which it operates are defined only in part. To unravel importin-β's mitotic functions we have developed cell lines expressing either wild-type or a mutant importin-β form in characterised residues required for nucleoporin binding. Both forms similarly disrupted spindle pole organisation, while only wild-type importin-β affected microtubule plus-end function and microtubule stability. A proteome-wide search for differential interactors identified a set of spindle regulators sensitive to mutations in the nucleoporin-binding region. Among those, HURP (hepatoma up-regulated protein) is an importin-β interactor and a microtubule-stabilising factor. We found that induction of wild type, but not mutant importin-β, under the same conditions that destabilise mitotic microtubules, delocalised HURP, indicating that the spatial distribution of HURP along the spindle requires importin-β's nucleoporin-binding residues. Concomitantly, importin-β overexpression sensitises cells to taxanes and synergistically increases mitotic cell death. Thus, the nucleoporin-binding domain is dispensable for importin-β function in spindle pole organisation, but regulates microtubule stability, at least in part via HURP, and renders cells vulnerable to certain microtubule-targeting drugs.
journal_name
Oncogenejournal_title
Oncogeneauthors
Verrico A,Rovella P,Di Francesco L,Damizia M,Staid DS,Le Pera L,Schininà ME,Lavia Pdoi
10.1038/s41388-019-0989-xsubject
Has Abstractpub_date
2020-01-01 00:00:00pages
454-468issue
2eissn
0950-9232issn
1476-5594pii
10.1038/s41388-019-0989-xjournal_volume
39pub_type
杂志文章相关文献
ONCOGENE文献大全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::Collagenase1 (MMP1) and stromelysin1 (MMP3) are extracellular proteolytic enzymes that degrade connective tissue macromolecules and basement membranes. Both genes are regulated by the Ets and Fos/Jun families of transcription factors/oncoproteins. Here, we show that two members of the Ets-family, Ets2 and Erg and thei...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1996-12-05 00:00:00
abstract::RNA polymerase (pol) III synthesizes a range of essential products, including tRNA, 5S rRNA and 7SL RNA, which are required for protein synthesis and trafficking. High rates of pol III transcription are necessary for cells to sustain growth. A wide range of transformed and tumour cell types have been shown to express ...
journal_title:Oncogene
pub_type: 杂志文章,评审
doi:10.1038/sj.onc.1207547
更新日期:2004-04-19 00:00:00
abstract::Prothymosin alpha (PT-alpha) is a nuclear protein involved in cell proliferation. Transcription of PT-alpha has been reported to be regulated by the c-myc gene in vitro. We identified PT-alpha as being overexpressed in a human colon cancer minus normal mucosa subtraction cDNA library. Northern blot (messenger RNA) ana...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1993-10-01 00:00:00
abstract::The aspartic protease cathepsin D (cath-D) is a key mediator of induced-apoptosis and its proteolytic activity has been generally involved in this event. During apoptosis, cath-D is translocated to the cytosol. Because cath-D is one of the lysosomal enzymes that requires a more acidic pH to be proteolytically active r...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1209221
更新日期:2006-03-23 00:00:00
abstract::The p21WAF1/CIP1/SDI1 gene is an important regulator of crucial cellular processes, including cell cycle control, cellular differentiation, and the response to genotoxic stress. Induction of p21 gene expression upon DNA damage is widely believed to be p53-dependent. In the present study we analysed the expression of p...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1201995
更新日期:1998-08-13 00:00:00
abstract::We previously showed that the proto-oncogene RON encodes the tyrosine kinase receptor for Macrophage Stimulating Protein (MSP), originally isolated as a chemotactic factor for peritoneal macrophages. To elucidate the biological role of MSP we studied the expression of the Ron receptor in vivo, and the response to the ...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1995-12-21 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::Nerve growth factor induces differentiation and survival of rat PC12 pheochromocytoma cells. The activation of the erk cascade has been implicated in transducing the multitude of signals induced by NGF. In order to explore the role of this signaling cascade in NGF mediated survival, differentiation and proliferation, ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1202524
更新日期:1999-03-25 00:00:00
abstract::Accumulating evidences have shown the association between aberrantly expressed microRNAs (miRs) and cancer, where these small regulatory RNAs appear to dictate the cell fate by regulating all the main biological processes. We demonstrated the responsibility of the circuitry connecting the oncomiR-221&222 with the tumo...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2015.357
更新日期:2016-06-09 00:00:00
abstract::Paxillin (PXN), a key component of the focal adhesion complex, has been associated with cancer progression, but the underlying mechanisms are poorly understood. The purpose of this study was to elucidate mechanisms by which PXN affects cancer growth and progression, which we addressed using cancer patient data, cell l...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/s41388-020-01517-3
更新日期:2021-01-01 00:00:00
abstract::We have evaluated the transcriptional activation of a human p21 promoter reporter construct by transfection of BRCA1 expression constructs into tumorigenic and nontumorigenic human breast cell lines. Two cell lines with wildtype p53 (MCF-7 and MCF10A) demonstrated transcriptional activation of the p21 promoter by full...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1204025
更新日期:2000-12-14 00:00:00
abstract::The degree of DNA methylation in the c-fos gene and its vicinity in liver, brain and spleen of mice of different ages was examined using methylation-sensitive restriction endonucleases. The gene had an invariable unmethylated domain from 1.8kb upstream of the cap site to the first intron. The domain was flanked on bot...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1989-08-01 00:00:00
abstract::The role of p53 in genotoxic therapy-induced metabolic shift in cancers is not yet known. In this study, we investigated the role of p53 in the glycolytic shift in head and neck squamous cell carcinoma cell lines following irradiation. Isogenic p53-null radioresistant cancer cells established through cumulative irradi...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/s41388-019-0697-6
更新日期:2019-05-01 00:00:00
abstract::Using a combination of raf and myc oncogenes co-expressed by the recombinant retrovirus J-2 we have generated and characterized a cell line which very efficiently supports the growth of B-cells and B-cell hybridomas. Murine spleen cells were cultured under in vitro immunization conditions favoring the short term proli...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1990-09-01 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::Pin1 regulates a subset of phosphoproteins by isomerizing phospho-Ser/Thr-Pro motifs via a 'post-phosphorylation' mechanism. Here, we characterize TR3 as a novel Pin1 substrate, and the mitogenic function of TR3 depends on Pin1-induced isomerization. There are at least three phospho-Ser-Pro motifs on TR3 that bind to ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2011.463
更新日期:2012-06-07 00:00:00
abstract::The metastasis-associated protein 1 (MTA1) is overexpressed in various human cancers and is closely connected with aggressive phenotypes; however, little is known about the transcriptional regulation of the MTA1 gene. This study identified the MTA1 gene as a target of p53-mediated transrepression. The MTA1 promoter co...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2012.2
更新日期:2012-12-06 00:00:00
abstract::Hepatocyte nuclear factor 4alpha (HNF4alpha) is a tissue-specific transcription factor known to regulate a large number of genes in hepatocytes and pancreatic beta cells. Although HNF4alpha is highly expressed in some sections of the kidney, little is known about its role in this organ and about HNF4alpha-regulated ge...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1208794
更新日期:2005-09-22 00:00:00
abstract::Amplified segments of the long arm of chromosome 12 are frequently observed in human sarcomas. In most cases there are separate amplified regions around the MDM2 and CDK4 genes. Here we show recurrent amplification of a third region encompassing HMGIC, a human architectural transcription factor gene. Reduced amplifica...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1201135
更新日期:1997-06-19 00:00:00
abstract::The sirtuins (SIRT 1-7) comprise a family of NAD⁺-dependent protein-modifying enzymes with activities in lysine deacetylation, adenosinediphospho(ADP)-ribosylation, and/or deacylation. These enzymes are involved in the cell's stress response systems and in regulating gene expression, DNA damage repair, metabolism and ...
journal_title:Oncogene
pub_type: 杂志文章,评审
doi:10.1038/onc.2013.120
更新日期:2014-03-27 00:00:00
abstract::The role of intracellular Ca2+ pools in the regulation of growth factor signal transduction pathways and mitogenesis is not well understood. We have examined the roles of basal and transiently mobilized Ca2+ in the regulation of MAP kinases by EGF. To assess the influence of Ca2+ transients we utilized Plcg1-/- and Pl...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1203517
更新日期:2000-03-30 00:00:00
abstract::The Notch ligand delta-like ligand 4 (DLL4) is an essential component expressed by endothelial tip cells during angiogenic sprouting. We have described a conceptually novel therapeutic strategy for targeting tumor angiogenesis and endothelial tip cells based on DNA vaccination against DLL4. Immunization with DLL4-enco...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2010.176
更新日期:2010-07-29 00:00:00
abstract::Amplification and rearrangements of the epidermal growth factor receptor (EGFR) gene are frequently found in glioblastoma multiforme (GBM). The most common variant is EGFR variant III (EGFRvIII). Research suggests that EGFRvIII could be a marker for a cancer stem cell or tumor-initiating population. If amplification a...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2012.280
更新日期:2013-05-23 00:00:00
abstract::The p53 tumor suppressor protein plays a central role in maintaining genomic integrity by occupying a nodal point in the DNA damage control pathway. Here it integrates a wide variety of signals, responding in one of several ways, that is, cell cycle arrest, senescence or programmed cell death (apoptosis). Mutations in...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1209952
更新日期:2007-03-08 00:00:00
abstract::Evidence from murine fibroblast models and human breast cancer cells indicates that c-Src and human EGF receptor (HER1) synergize to enhance neoplastic growth of mammary epithelial cells. To investigate whether interactions between c-Src and other HER family members may also play a role in breast tumor progression, we...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1204205
更新日期:2001-03-22 00:00:00
abstract::We have previously reported that there is a high incidence of microsatellite instability (MSI) and germline mismatch repair gene mutation in colorectal cancer arising from young Hong Kong Chinese. Most of the germline mutations involve hMSH2, which is different from the mutation spectrum in the Western population. It ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1204376
更新日期:2001-05-24 00:00:00
abstract::To investigate the mechanisms of colorectal carcinogenesis, we searched for genes regulated by adenomatous polyposis coli gene product (APC) and identified a novel gene, termed HELAD1 (helicase, APC down-regulated 1). A recombinant polypeptide representing the ATPases associated with cellular activities (AAA) domain o...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1205751
更新日期:2002-09-12 00:00:00
abstract::Ufo/Axl belongs to a new family of receptor tyrosine kinases with an extracellular structure similar to that of neural cell adhesion molecules. In order to elucidate intracellular signaling, the cytoplasmic moiety of Ufo/Axl was used to screen an expression library according to the CORT (cloning of receptor targets) m...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1201123
更新日期:1997-06-05 00:00:00
abstract::We previously reported the presence of mitotic check-point impairment in about 40% of lung cancer cell lines. To gain an insight into the molecular basis of this impairment, we examined 49 lung cancer specimens for alterations in the hMAD1 mitotic checkpoint gene and identified a somatic, non-conservative missense mut...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1203141
更新日期:1999-11-25 00:00:00