p53-dependent senescence delays Emu-myc-induced B-cell lymphomagenesis.

Abstract:

:The effect of p53-dependent cell-cycle arrest and senescence on Emu-myc-induced B-cell lymphoma development remains controversial. To address this question, we crossed Emu-myc mice with the p53(515C) mutant mouse, encoding the mutant p53R172P protein that retains the ability to activate the cell-cycle inhibitor and senescence activator p21. Importantly, this mutant lacks the ability to activate p53-dependent apoptotic genes. Hence, Emu-myc mice that harbor two p53(515C) alleles are completely defective for p53-dependent apoptosis. Both Emu-myc::p53(515C/515C) and Emu-myc::p53(515C/+) mice survive significantly longer than Emu-myc::p53(+/-) mice, indicating the importance of the p53-dependent non-apoptotic pathways in B-cell lymphomagenesis. In addition, the p53(515C) allele is deleted in several Emu-myc::p53(515C/+) lymphomas, further emphasizing the functionality of p53R172P in tumor inhibition. Lymphomas from both Emu-myc::p53(515C/515C) and Emu-myc::p53(515C/+) mice retain the ability to upregulate p21, resulting in cellular senescence. Senescence-associated beta-galactosidase (SA beta-gal) activity was observed in lymphomas from Emu-myc::p53(+/+), Emu-myc::p53(515C/515C) and Emu-myc::p53(515C /+) mice but not in lymphomas isolated from Emu-myc::p53(+/-) mice. Thus, in the absence of p53-dependent apoptosis, the ability of p53R172P to induce senescence leads to a significant delay in B-cell lymphoma development.

journal_name

Oncogene

journal_title

Oncogene

authors

Post SM,Quintás-Cardama A,Terzian T,Smith C,Eischen CM,Lozano G

doi

10.1038/onc.2009.423

subject

Has Abstract

pub_date

2010-03-04 00:00:00

pages

1260-9

issue

9

eissn

0950-9232

issn

1476-5594

pii

onc2009423

journal_volume

29

pub_type

杂志文章

相关文献

ONCOGENE文献大全
  • Mutant fibroblast growth factor receptor 3 induces intracellular signaling and cellular transformation in a cell type- and mutation-specific manner.

    abstract::Although activating mutations of fibroblast growth factor receptor 3 (FGFR3) are frequent in bladder tumors, little information is available on their specific effects in urothelial cells or the basis for the observed mutation spectrum. We investigated the phenotypic and signaling consequences of three FGFR3 mutations ...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2009.280

    authors: di Martino E,L'Hôte CG,Kennedy W,Tomlinson DC,Knowles MA

    更新日期:2009-12-03 00:00:00

  • The role of MAP4 expression in the sensitivity to paclitaxel and resistance to vinca alkaloids in p53 mutant cells.

    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

    authors: Zhang CC,Yang JM,White E,Murphy M,Levine A,Hait WN

    更新日期:1998-03-26 00:00:00

  • SCF-mediated protein degradation and cell cycle control.

    abstract::The regulatory step in ubiquitin (Ub)-mediated protein degradation involves recognition and selection of the target substrate by an E3 Ub-ligase. E3 Ub-ligases evoke sophisticated mechanisms to regulate their activity temporally and spatially, including multiple post-translational modifications, combinatorial E3 Ub-li...

    journal_title:Oncogene

    pub_type: 杂志文章,评审

    doi:10.1038/sj.onc.1208614

    authors: Ang XL,Wade Harper J

    更新日期:2005-04-18 00:00:00

  • Pleiotropic regulation of macrophage polarization and tumorigenesis by formyl peptide receptor-2.

    abstract::Cancer cells recruit monocytes, macrophages and other inflammatory cells by producing abundant chemoattractants and growth factors, such as macrophage colony-stimulating factor (M-CSF/CSF-1) and monocyte chemoattractant protein-1 (MCP-1/CCL2), to promote tumor growth and dissemination. An understanding of the mechanis...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2011.112

    authors: Li Y,Cai L,Wang H,Wu P,Gu W,Chen Y,Hao H,Tang K,Yi P,Liu M,Miao S,Ye D

    更新日期:2011-09-08 00:00:00

  • Alterations in the common fragile site gene Parkin in ovarian and other cancers.

    abstract::The cloning and characterization of the common fragile site (CFS) FRA6E (6q26) identified Parkin, the gene involved in the pathogenesis of many cases of juvenile, early-onset and, rarely, late-onset Parkinson's disease, as the third large gene to be localized within a large CFS. Initial analyses of Parkin indicated th...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1207072

    authors: Denison SR,Wang F,Becker NA,Schüle B,Kock N,Phillips LA,Klein C,Smith DI

    更新日期:2003-11-13 00:00:00

  • Expression of normal and mutant ras proteins in human acute leukemia.

    abstract::The expression of normal and mutant ras genes in human acute leukemias was assessed by the direct analysis of p21ras polypeptides, using immunoprecipitation with monoclonal antibodies. High-resolution two-dimensional gel electrophoresis permits the identification of a wide array of activated ras alleles encoding prote...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:

    authors: Shen WP,Aldrich TH,Venta-Perez G,Franza BR Jr,Furth ME

    更新日期:1987-05-01 00:00:00

  • Low doses of decitabine improve the chemotherapy efficacy against basal-like bladder cancer by targeting cancer stem cells.

    abstract::Low dose treatment with the DNA methylation inhibitor decitabine has been shown to be applicable for the management of certain types of cancer. However, its antitumor effect and mechanisms are context dependent and its activity has never been systematically studied in bladder cancer treatment. We used mouse models, cu...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/s41388-019-0799-1

    authors: Wu M,Sheng L,Cheng M,Zhang H,Jiang Y,Lin S,Liang Y,Zhu F,Liu Z,Zhang Y,Zhang X,Gao Q,Chen D,Li J,Li Y

    更新日期:2019-07-01 00:00:00

  • Integrative analysis of genomic amplification-dependent expression and loss-of-function screen identifies ASAP1 as a driver gene in triple-negative breast cancer progression.

    abstract::The genetically heterogeneous triple-negative breast cancer (TNBC) continues to be an intractable disease, due to lack of effective targeted therapies. Gene amplification is a major event in tumorigenesis. Genes with amplification-dependent expression are being explored as therapeutic targets for cancer treatment. In ...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/s41388-020-1279-3

    authors: He J,McLaughlin RP,van der Beek L,Canisius S,Wessels L,Smid M,Martens JWM,Foekens JA,Zhang Y,van de Water B

    更新日期:2020-05-01 00:00:00

  • Endoglin (CD105): a powerful therapeutic target on tumor-associated angiogenetic blood vessels.

    abstract::Among surface molecules expressed on endothelial cells, endoglin (CD105) is emerging as a prime vascular target for antiangiogenetic cancer therapy. CD105 is a cell membrane glycoprotein mainly expressed on endothelial cells and overexpressed on tumor-associated vascular endothelium, which functions as an accessory co...

    journal_title:Oncogene

    pub_type: 杂志文章,评审

    doi:10.1038/sj.onc.1206813

    authors: Fonsatti E,Altomonte M,Nicotra MR,Natali PG,Maio M

    更新日期:2003-09-29 00:00:00

  • Elimination of chronic lymphocytic leukemia cells in stromal microenvironment by targeting CPT with an antiangina drug perhexiline.

    abstract::Chronic lymphocytic leukemia (CLL) is the most common adult leukemia in the western countries and is currently incurable due, in part, to difficulty in eliminating the leukemia cells protected by stromal microenvironment. Based on previous observations that CLL cells exhibit mitochondrial dysfunction and altered lipid...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2016.103

    authors: Liu PP,Liu J,Jiang WQ,Carew JS,Ogasawara MA,Pelicano H,Croce CM,Estrov Z,Xu RH,Keating MJ,Huang P

    更新日期:2016-10-27 00:00:00

  • SPARC, an extracellular matrix protein with tumor-suppressing activity in human ovarian epithelial cells.

    abstract::SPARC, also termed osteonectin, BM-40 and 43K protein, is an acidic, cysteine-rich component of the extracellular matrix that has been shown to be directly regulated by progesterone and dexamethasone and indirectly by cytokines. By RNA fingerprinting technique, we cloned a SPARC homolog from the normal human ovarian s...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:

    authors: Mok SC,Chan WY,Wong KK,Muto MG,Berkowitz RS

    更新日期:1996-05-02 00:00:00

  • Oncology studies using siRNA libraries: the dawn of RNAi-based genomics.

    abstract::High-throughput, human cell-based applications of RNA-mediated interference (RNAi) have emerged in recent years as perhaps the most powerful of a 'second wave' of functional genomics technologies. The available reagents and methodologies for RNAi screening studies now enable a wide range of different scopes and scales...

    journal_title:Oncogene

    pub_type: 杂志文章,评审

    doi:10.1038/sj.onc.1208072

    authors: Sachse C,Echeverri CJ

    更新日期:2004-11-01 00:00:00

  • Cyclin D1 and D3 associate with the SCF complex and are coordinately elevated in breast cancer.

    abstract::D-type cyclins are important cell cycle regulators that promote cellular proliferation in response to growth factors by inactivation of the retinoblastoma protein (Rb). Cyclin D1 has been shown to be overexpressed in several cancer types and to act as an oncogene in breast cancers. As D-type cyclins are rate limiting ...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1202511

    authors: Russell A,Thompson MA,Hendley J,Trute L,Armes J,Germain D

    更新日期:1999-03-18 00:00:00

  • β-catenin S45F mutation results in apoptotic resistance.

    abstract::Wnt/β-catenin signaling is one of the key cascades regulating embryogenesis and tissue homeostasis; it has also been intimately associated with carcinogenesis. This pathway is deregulated in several tumors, including colorectal cancer, breast cancer, and desmoid tumors. It has been shown that CTNNB1 exon 3 mutations a...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/s41388-020-1382-5

    authors: Braggio D,Zewdu A,Londhe P,Yu P,Lopez G,Batte K,Koller D,Costas Casal de Faria F,Casadei L,Strohecker AM,Lev D,Pollock RE

    更新日期:2020-08-01 00:00:00

  • PKA signaling drives mammary tumorigenesis through Src.

    abstract::Protein kinase A (PKA) hyperactivation causes hereditary endocrine neoplasias; however, its role in sporadic epithelial cancers is unknown. Here, we show that heightened PKA activity in the mammary epithelium generates tumors. Mammary-restricted biallelic ablation of Prkar1a, which encodes for the critical type-I PKA ...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2014.41

    authors: Beristain AG,Molyneux SD,Joshi PA,Pomroy NC,Di Grappa MA,Chang MC,Kirschner LS,Privé GG,Pujana MA,Khokha R

    更新日期:2015-02-26 00:00:00

  • The EBV-encoded LMP1 protein inhibits p53-triggered apoptosis but not growth arrest.

    abstract::We have previously shown that exogenous wild type p53 induces apoptosis in the Burkitt lymphoma line BL41 that carries endogenous mutant p53, using a temperature sensitive p53 construct expressed as mutant p53 at 37 degrees C and wild type p53 at 32 degrees C (Ramqvist et al., Oncogene, 8, 1495-1500, 1993). We also fo...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:

    authors: Okan I,Wang Y,Chen F,Hu LF,Imreh S,Klein G,Wiman KG

    更新日期:1995-09-21 00:00:00

  • Histone deacetylase associated with mSin3A mediates repression by the acute promyelocytic leukemia-associated PLZF protein.

    abstract::The PLZF gene was identified first by its fusion with the retinoic acid receptor alpha gene in the t(11;17) translocation associated with a retinoic acid resistant form of acute promyelocytic leukemia (APL). It encodes a krüppel-like zinc finger protein with a POZ domain shared with a subset of regulatory proteins inc...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1202043

    authors: David G,Alland L,Hong SH,Wong CW,DePinho RA,Dejean A

    更新日期:1998-05-14 00:00:00

  • Upregulation of IKKalpha/IKKbeta by integrin-linked kinase is required for HER2/neu-induced NF-kappaB antiapoptotic pathway.

    abstract::Constitutively active HER2/neu activates nuclear factor kappa-B (NF-kappaB) in cells and induces their resistance to apoptotic stimuli such as tumor necrosis factor-alpha (TNF-alpha). Here, we show that integrin-linked kinase (ILK), the crucial signal transducer in the integrin pathway, is involved in HER2/neu-mediate...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1207485

    authors: Makino K,Day CP,Wang SC,Li YM,Hung MC

    更新日期:2004-05-06 00:00:00

  • G-proteins in growth and apoptosis: lessons from the heart.

    abstract::The acute contractile function of the heart is controlled by the effects of released nonepinephrine (NE) on cardiac adrenergic receptors. NE can also act in a more chronic fashion to induce cardiomyocyte growth, characterized by cell enlargement (hypertrophy), increased protein synthesis, alterations in gene expressio...

    journal_title:Oncogene

    pub_type: 杂志文章,评审

    doi:10.1038/sj.onc.1204275

    authors: Adams JW,Brown JH

    更新日期:2001-03-26 00:00:00

  • Central roles of apoptotic proteins in mitochondrial function.

    abstract::Mitochondria have been classically characterized as organelles with responsibility for cellular energy production in the form of ATP, but they are also the organelles through which apoptotic signaling occurs. Cell stress stimuli can result in outer membrane permeabilization, after which mitochondria release numerous p...

    journal_title:Oncogene

    pub_type: 杂志文章,评审

    doi:10.1038/onc.2012.348

    authors: Kilbride SM,Prehn JH

    更新日期:2013-05-30 00:00:00

  • The rapid destabilization of p53 mRNA in immortal chicken embryo fibroblast cells.

    abstract::The steady-state levels of p53 mRNA were dramatically lower in immortal chicken embryo fibroblast (CEF) cell lines compared to primary CEF cells. In the presence of cycloheximide (CHX), the steady-state levels of p53 mRNA markedly increased in immortal CEF cell lines, similar to levels found in primary cells. The de n...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1204664

    authors: Kim H,You S,Foster LK,Farris J,Foster DN

    更新日期:2001-08-23 00:00:00

  • PKCmu prevents CD95-mediated apoptosis and enhances proliferation in pancreatic tumour cells.

    abstract::Loss of growth control and a marked resistance to apoptosis are considered major mechanisms driving tumour progression. Protein kinases C (PKC) have been shown to be important in the regulation of proliferation and apoptosis. In this report, we investigated the role of the PKC-like kinase PKCmu in the control of these...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1207001

    authors: Trauzold A,Schmiedel S,Sipos B,Wermann H,Westphal S,Röder C,Klapper W,Arlt A,Lehnert L,Ungefroren H,Johannes FJ,Kalthoff H

    更新日期:2003-12-04 00:00:00

  • The FEN1 E359K germline mutation disrupts the FEN1-WRN interaction and FEN1 GEN activity, causing aneuploidy-associated cancers.

    abstract::Polymorphisms and somatic mutations in Flap Endonuclease 1 (FEN1), an essential enzyme involved in DNA replication and repair, can lead to functional deficiencies of the FEN1 protein and a predisposition to cancer. We identified a FEN1 germline mutation that changed residue E359 to K in a patient whose family had a hi...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2014.19

    authors: Chung L,Onyango D,Guo Z,Jia P,Dai H,Liu S,Zhou M,Lin W,Pang I,Li H,Yuan YC,Huang Q,Zheng L,Lopes J,Nicolas A,Chai W,Raz D,Reckamp KL,Shen B

    更新日期:2015-02-12 00:00:00

  • MEMO1, a new IRS1-interacting protein, induces epithelial-mesenchymal transition in mammary epithelial cells.

    abstract::MEMO1 (mediator of ErbB2-driven cell motility 1) regulates HER2-dependent cell migration. Increased MEMO1 expression is associated with cancer aggressiveness. Here, we found that MEMO1 is also involved in breast carcinogenesis via regulating insulin-like growth factor-I receptor-dependent signaling events. We showed t...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2012.327

    authors: Sorokin AV,Chen J

    更新日期:2013-06-27 00:00:00

  • Transcript map and complete genomic sequence for the 310 kb region of minimal allele loss on chromosome segment 11p15.5 in non-small-cell lung cancer.

    abstract::Molecular, functional, and clinical analyses strongly suggest that chromosome segment 11p15.5 contains a gene involved in lung cancer pathogenesis. The critical region of allele loss is 310 kb in size. We used our contig of P1-phage artificial chromosome (PAC) clones together with newly identified bacterial artificial...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1205027

    authors: Zhao B,Bepler G

    更新日期:2001-12-06 00:00:00

  • TAp63gamma (p51A) and dNp63alpha (p73L), two major isoforms of the p63 gene, exert opposite effects on the vascular endothelial growth factor (VEGF) gene expression.

    abstract::Tumor suppressor p53 has been shown to repress expression of vascular endothelial growth factor (VEGF), an endothelial cell-specific mitogen and a key mediator of tumor angiogenesis. The p63 gene, recently identified as a p53-relative, encodes multiple isoforms with structural and functional similarities and differenc...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1205330

    authors: Senoo M,Matsumura Y,Habu S

    更新日期:2002-04-11 00:00:00

  • SUV39H1 regulates the progression of MLL-AF9-induced acute myeloid leukemia.

    abstract::Epigenetic regulations play crucial roles in leukemogenesis and leukemia progression. SUV39H1 is the dominant H3K9 methyltransferase in the hematopoietic system, and its expression declines with aging. However, the role of SUV39H1 via its-mediated repressive modification H3K9me3 in leukemogenesis/leukemia progression ...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/s41388-020-01495-6

    authors: Chu Y,Chen Y,Guo H,Li M,Wang B,Shi D,Cheng X,Guan J,Wang X,Xue C,Cheng T,Shi J,Yuan W

    更新日期:2020-12-01 00:00:00

  • Isolation of expressed sequences that include a gene for familial breast cancer (BRCA2) and other novel transcripts from a five megabase region on chromosome 13q12.

    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:

    authors: Jacob AN,Kandpal G,Kandpal RP

    更新日期:1996-07-04 00:00:00

  • Narrow spectrum of infrequent p53 mutations and absence of MDM2 amplification in Ewing tumours.

    abstract::The p53 and MDM2 genes are part of a physiological pathway frequently impaired in human cancer. With the exception of tumours occasionally associated with hereditary predisposition, childhood malignancies have not been studied in detail yet. This is the first report on the analysis of p53 and MDM2 in a group of non-he...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:

    authors: Kovar H,Auinger A,Jug G,Aryee D,Zoubek A,Salzer-Kuntschik M,Gadner H

    更新日期:1993-10-01 00:00:00

  • DNA adduct burden and tobacco carcinogenesis.

    abstract::DNA adducts associated with tobacco smoking could provide a marker of biologically effective dose of tobacco carcinogens and improve individual cancer risk prediction. A significant number of clinical and epidemiologic studies have reported associations of increased DNA adduct levels with the occurrence of the prevale...

    journal_title:Oncogene

    pub_type: 杂志文章,评审

    doi:10.1038/sj.onc.1205799

    authors: Wiencke JK

    更新日期:2002-10-21 00:00:00