Random mutagenesis of PDZ(Omi) domain and selection of mutants that specifically bind the Myc proto-oncogene and induce apoptosis.

Abstract:

:Omi is a mammalian serine protease that is localized in the mitochondria and released to the cytoplasm in response to apoptotic stimuli. Omi induces cell death in a caspase-dependent manner by interacting with the X-chromosome linked inhibitor of apoptosis protein, as well as in a caspase-independent way that relies on its proteolytic activity. Omi is synthesized as a precursor polypeptide and is processed to an active serine protease with a unique PDZ domain. PDZ domains recognize the extreme carboxyl terminus of target proteins. Internal peptides that are able to fold into a beta-finger are also reported to bind some PDZ domains. Using a modified yeast two-hybrid system, PDZ(Omi) mutants were isolated by their ability to bind the carboxyl terminus of human Myc oncoprotein in yeast as well as in mammalian cells. One such PDZ(m) domain (PDZ-M1), when transfected into mammalian cells, was able to bind to endogenous Myc protein and induce cell death. PDZ-M1-induced apoptosis was entirely dependent on the presence of Myc protein and was not observed when c-myc null fibroblasts were used. Our studies indicate that the PDZ domain of Omi can provide a prototype that could easily be exploited to target specifically and inactivate oncogenes by binding to their unique carboxyl terminus.

journal_name

Oncogene

journal_title

Oncogene

authors

Junqueira D,Cilenti L,Musumeci L,Sedivy JM,Zervos AS

doi

10.1038/sj.onc.1206359

subject

Has Abstract

pub_date

2003-05-08 00:00:00

pages

2772-81

issue

18

eissn

0950-9232

issn

1476-5594

pii

1206359

journal_volume

22

pub_type

杂志文章

相关文献

ONCOGENE文献大全
  • Paclitaxel-induced apoptosis in BJAB cells proceeds via a death receptor-independent, caspases-3/-8-driven mitochondrial amplification loop.

    abstract::Caspase-8 is a key effector of death-receptor-triggered apoptosis. In a previous study, we demonstrated, however, that caspase-8 can also be activated in a death receptor-independent manner via the mitochondrial apoptosis pathway, downstream of caspase-3. Here, we show that caspases-3 and -8 mediate a mitochondrial am...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1206280

    authors: von Haefen C,Wieder T,Essmann F,Schulze-Osthoff K,Dörken B,Daniel PT

    更新日期:2003-04-17 00:00:00

  • Identification of expressed genes characterizing long-term survival in malignant glioma patients.

    abstract::Better understanding of the underlying biology of malignant gliomas is critical for the development of early detection strategies and new therapeutics. This study aimed to define genes associated with survival. We investigated whether genes coupled with a class prediction model could be used to define subgroups of hig...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1209585

    authors: Yamanaka R,Arao T,Yajima N,Tsuchiya N,Homma J,Tanaka R,Sano M,Oide A,Sekijima M,Nishio K

    更新日期:2006-09-28 00:00:00

  • WAVE3, an actin-polymerization gene, is truncated and inactivated as a result of a constitutional t(1;13)(q21;q12) chromosome translocation in a patient with ganglioneuroblastoma.

    abstract::Neuroblastoma (Nb) is a malignancy of the sympathetic nervous system which affects children in their first decade. It is the most common extra-cranial solid tumor in children with an incidence of approximately 1 in 8-10 000 live births annually and accounts for approximately 10% of all children's cancers. Ganglioneuro...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1205734

    authors: Sossey-Alaoui K,Su G,Malaj E,Roe B,Cowell JK

    更新日期:2002-08-29 00:00:00

  • The phosphatidylinositol 3' kinase pathway is required for the survival signal of leukocyte tyrosine kinase.

    abstract::Leukocyte tyrosine kinase (LTK) is a receptor tyrosine kinase which belongs to the insulin receptor superfamily and is mainly expressed in pre-B lymphocytes and neuronal tissues. Recently, we demonstrated that LTK utilizes Shc and IRS-1 as two major substrates and while both equally activate the Ras pathway, only IRS-...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1201153

    authors: Ueno H,Honda H,Nakamoto T,Yamagata T,Sasaki K,Miyagawa K,Mitani K,Yazaki Y,Hirai H

    更新日期:1997-06-26 00:00:00

  • Cancer whole-genome sequencing: present and future.

    abstract::Recent explosive advances in next-generation sequencing technology and computational approaches to massive data enable us to analyze a number of cancer genome profiles by whole-genome sequencing (WGS). To explore cancer genomic alterations and their diversity comprehensively, global and local cancer genome-sequencing ...

    journal_title:Oncogene

    pub_type: 杂志文章,评审

    doi:10.1038/onc.2015.90

    authors: Nakagawa H,Wardell CP,Furuta M,Taniguchi H,Fujimoto A

    更新日期:2015-12-03 00:00:00

  • An integrative analysis reveals functional targets of GATA6 transcriptional regulation in gastric cancer.

    abstract::Lineage-restricted transcription factors (TFs) are frequently mutated or overexpressed in cancer and contribute toward malignant behaviors; however, the molecular bases of their oncogenic properties are largely unknown. As TF activities are difficult to inhibit directly with small molecules, the genes and pathways the...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2013.517

    authors: Sulahian R,Casey F,Shen J,Qian ZR,Shin H,Ogino S,Weir BA,Vazquez F,Liu XS,Hahn WC,Bass AJ,Chan V,Shivdasani RA

    更新日期:2014-12-04 00:00:00

  • Structural analysis of the human nov proto-oncogene and expression in Wilms tumor.

    abstract::We have cloned and sequenced the nov gene (novH) which is the homolog of the chicken nov proto-oncogene overexpressed in avian nephroblastomas. The novH gene is highly conserved and encodes a putative IGF-binding protein similar to that of chicken. We report that relative to autologous normal kidney expression of novH...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:

    authors: Martinerie C,Huff V,Joubert I,Badzioch M,Saunders G,Strong L,Perbal B

    更新日期:1994-09-01 00:00:00

  • Involvement of EGF receptor and c-Src in the survival signals induced by TGF-beta1 in hepatocytes.

    abstract::Transforming growth factor beta1 (TGF-beta1) belongs to a family of polypeptide factors, whose cytostatic and apoptotic functions help restrain the growth of mammalian cells. Although solid data established the role of TGF-beta's as suppressor factors in tumorigenic processes, in the context of an advanced stage of di...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1208664

    authors: Murillo MM,del Castillo G,Sánchez A,Fernández M,Fabregat I

    更新日期:2005-06-30 00:00:00

  • Activation of the Ras signalling pathway in human breast cancer cells overexpressing erbB-2.

    abstract::The c-erbB-2 proto-oncogene encodes a receptor tyrosine kinase (RTK) closely related to the epidermal growth factor receptor (EGFR). Overexpression of erbB-2 occurs in approximately 20% of human breast tumours, where increased expression correlates with poor patient prognosis. The EGFR is coupled to the Ras signalling...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:

    authors: Janes PW,Daly RJ,deFazio A,Sutherland RL

    更新日期:1994-12-01 00:00:00

  • Knock in of the AKT1 E17K mutation in human breast epithelial cells does not recapitulate oncogenic PIK3CA mutations.

    abstract::An oncogenic mutation (G49A:E17K) in the AKT1 gene has been described recently in human breast, colon, and ovarian cancers. The low frequency of this mutation and perhaps other selective pressures have prevented the isolation of human cancer cell lines that harbor this mutation thereby limiting functional analysis. He...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2009.516

    authors: Lauring J,Cosgrove DP,Fontana S,Gustin JP,Konishi H,Abukhdeir AM,Garay JP,Mohseni M,Wang GM,Higgins MJ,Gorkin D,Reis M,Vogelstein B,Polyak K,Cowherd M,Buckhaults PJ,Park BH

    更新日期:2010-04-22 00:00:00

  • Polyoma virus disrupts ARF signaling to p53.

    abstract::Polyoma virus (Py) differs from other small DNA tumor viruses in not encoding a protein that inactivates p53. The complete Py early region encoding the large T-antigen (PyLT), middle T-antigen (PyMT) and small T-antigen (PyST) will transform primary rodent cells and REF52 cells, but PyMT, the main Py oncogene, by itse...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1204717

    authors: Lomax M,Fried M

    更新日期:2001-08-16 00:00:00

  • Cyclin E in breast tumors is cleaved into its low molecular weight forms by calpain.

    abstract::Abundant levels of the hyperactive low molecular weight (LMW) forms of cyclin E contribute to deregulation of Cdk2 in breast tumors, but the mechanism through which they arise is not fully understood. Here, we explored the hypothesis that post-translational processing by a protease generates the LMW forms of cyclin E ...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1206166

    authors: Wang XD,Rosales JL,Magliocco A,Gnanakumar R,Lee KY

    更新日期:2003-02-06 00:00:00

  • Bcl-2 targeted to the endoplasmic reticulum can inhibit apoptosis induced by Myc but not etoposide in Rat-1 fibroblasts.

    abstract::Bcl-2 is a key inhibitor of a broad range of apoptotic pathways, yet neither the mechanism of action nor the role of Bcl-2 subcellular localization are well understood. The subcellular localization of Bcl-2 includes the mitochondrial membrane as well as the contiguous membrane of the endoplasmic reticulum and nuclear ...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1202716

    authors: Lee ST,Hoeflich KP,Wasfy GW,Woodgett JR,Leber B,Andrews DW,Hedley DW,Penn LZ

    更新日期:1999-06-10 00:00:00

  • Poly(ADP-ribose)-dependent regulation of Snail1 protein stability.

    abstract::Snail1 is a master regulator of the epithelial-mesenchymal transition (EMT) and has been implicated in key tumor biological processes such as invasion and metastasis. It has been previously shown that poly(ADP-ribose) polymerase-1 (PARP-1) knockdown, but not PARP inhibition, downregulates the expression of Snail1. In ...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2011.153

    authors: Rodríguez MI,González-Flores A,Dantzer F,Collard J,de Herreros AG,Oliver FJ

    更新日期:2011-10-20 00:00:00

  • Hepatic tumor-stroma crosstalk guides epithelial to mesenchymal transition at the tumor edge.

    abstract::The tumor-stroma crosstalk is a dynamic process fundamental in tumor development. In hepatocellular carcinoma (HCC), the progression of malignant hepatocytes frequently depends on transforming growth factor (TGF)-beta provided by stromal cells. TGF-beta induces an epithelial to mesenchymal transition (EMT) of oncogeni...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2009.253

    authors: van Zijl F,Mair M,Csiszar A,Schneller D,Zulehner G,Huber H,Eferl R,Beug H,Dolznig H,Mikulits W

    更新日期:2009-11-12 00:00:00

  • EGFR-STAT3 signaling promotes formation of malignant peripheral nerve sheath tumors.

    abstract::Malignant peripheral nerve sheath tumors (MPNSTs) develop sporadically or in the context of neurofibromatosis type 1. Epidermal growth factor receptor (EGFR) overexpression has been implicated in MPNST formation, but its precise role and relevant signaling pathways remain unknown. We found that EGFR overexpression pro...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2012.579

    authors: Wu J,Patmore DM,Jousma E,Eaves DW,Breving K,Patel AV,Schwartz EB,Fuchs JR,Cripe TP,Stemmer-Rachamimov AO,Ratner N

    更新日期:2014-01-09 00:00:00

  • Site-specific DNA methylation by a complex of PU.1 and Dnmt3a/b.

    abstract::The Ets transcription factor PU.1 is a hematopoietic master regulator essential for the development of myeloid and B-cell lineages. As we previously reported, PU.1 sometimes represses transcription on forming a complex with mSin3A-histone deacetyl transferase-MeCP2. Here, we show an interaction between PU.1 and DNA me...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1209272

    authors: Suzuki M,Yamada T,Kihara-Negishi F,Sakurai T,Hara E,Tenen DG,Hozumi N,Oikawa T

    更新日期:2006-04-20 00:00:00

  • p53 point mutation in HPV negative human cervical carcinoma cell lines.

    abstract::Clinical and experimental evidence is consistent with a key role for transforming human papilloma viruses (HPVs) in the aetiology of anogenital carcinoma. Cervical carcinoma does, however, occasionally occur in the absence of HPV sequences (Riou et al., 1990). We have used a direct cDNA/PCR sequencing protocol to anal...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:

    authors: Crook T,Wrede D,Vousden KH

    更新日期:1991-05-01 00:00:00

  • Diverse roles of STING-dependent signaling on the development of cancer.

    abstract::Stimulator of interferon genes (STING) is a cellular sensor that controls cytosolic DNA-activated innate immune signaling. We have previously demonstrated that STING-deficient mice are resistant to carcinogen-induced skin cancer, similar to myeloid differentiation primary response gene 88 (MyD88) deficient mice, since...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2014.457

    authors: Ahn J,Konno H,Barber GN

    更新日期:2015-10-08 00:00:00

  • Pim kinase-dependent inhibition of c-Myc degradation.

    abstract::Pim kinases are found to be highly expressed in leukemia, lymphoma, prostate and pancreatic cancer. Bitransgenic mice overexpressing either Pim-1 or Pim-2 and c-Myc succumb to pre-B-cell lymphoma at a strikingly accelerated speed. Despite that Pim-1/Pim-2 has long been recognized as a strong synergistic partner with c...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2008.123

    authors: Zhang Y,Wang Z,Li X,Magnuson NS

    更新日期:2008-08-14 00:00:00

  • To replicate or not to replicate: achieving selective oncolytic virus replication in cancer cells through translational control.

    abstract::To ensure that their mRNAs are translated and that the viral proteins necessary for assembling the next generation of infectious progeny are produced, viruses must effectively seize control of the translational machinery within their host cells. In many cases, the ability to productively engage host translational comp...

    journal_title:Oncogene

    pub_type: 杂志文章,评审

    doi:10.1038/sj.onc.1209053

    authors: Mohr I

    更新日期:2005-11-21 00:00:00

  • Failure of senescent cells to phosphorylate the RB protein.

    abstract::The product of the RB susceptibility gene has been shown to be differentially phosphorylated during the cell cycle, suggesting a role in the regulation of cell cycle progression. We examined the expression and phosphorylation status of the RB protein in senescent Syrian hamster embryo cells. Both phosphorylated and un...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:

    authors: Futreal PA,Barrett JC

    更新日期:1991-07-01 00:00:00

  • GSK3 beta mediates suppression of cyclin D2 expression by tumor suppressor PTEN.

    abstract::PTEN, encoding a lipid phosphatase, is a tumor suppressor gene and is mutated in various types of cancers. It is reported to regulate G1 to S phase transition of the cell cycle by influencing the expression, protein stability and subcellular location of cyclin D1. Here, we provide evidence that PTEN modulates the tran...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1210033

    authors: Huang W,Chang HY,Fei T,Wu H,Chen YG

    更新日期:2007-04-12 00:00:00

  • Tamoxifen induces p21WAF1 and p27KIP1 expression in estrogen receptor-negative lung cancer cells.

    abstract::Tamoxifen (Tam), besides its action as an anti-estrogen, also inhibits cell proliferation of estrogen receptor (ER)-negative cancer cells by an unknown mechanism. In this study, we used ER-negative lung cancer cells to clarify such ER-independent inhibitory effect of Tam. We found that Tam induced G1 growth arrest in ...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1202755

    authors: Lee TH,Chuang LY,Hung WC

    更新日期:1999-07-22 00:00:00

  • Identification of Elf-1 and B61 as high affinity ligands for the receptor tyrosine kinase MDK1.

    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

    authors: Ciossek T,Ullrich A

    更新日期:1997-01-09 00:00:00

  • C-myb proto-oncogene: evidence for intermolecular recombination of coding sequences.

    abstract::We have characterized a novel chicken c-myb exon whose sequences are specifically expressed in thymic cells. In situ hybridization experiments indicate that this thymus-specific coding exon is localized on a small chromosome, distinct from the large acrocentric chromosome 3 on which we recently mapped the bulk of 15 e...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:

    authors: Vellard M,Soret J,Viegas-Pequignot E,Galibert F,Nguyen VC,Dutrillaux B,Perbal B

    更新日期:1991-04-01 00:00:00

  • G-Quadruplex stabilization by telomestatin induces TRF2 protein dissociation from telomeres and anaphase bridge formation accompanied by loss of the 3' telomeric overhang in cancer cells.

    abstract::Inhibition of telomerase activity by telomerase inhibitors induces a gradual loss of telomeres, and this in turn causes cancer cells to enter to a crisis stage. Here, we report the telomerase inhibitor telomestatin, which is known to stabilize G-quadruplex structures at 3' single-stranded telomeric overhangs (G-tails)...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1209217

    authors: Tahara H,Shin-Ya K,Seimiya H,Yamada H,Tsuruo T,Ide T

    更新日期:2006-03-23 00:00:00

  • MYB regulates the DNA damage response and components of the homology-directed repair pathway in human estrogen receptor-positive breast cancer cells.

    abstract::Over 70% of human breast cancers are estrogen receptor-positive (ER+), most of which express MYB. In these and other cell types, the MYB transcription factor regulates the expression of many genes involved in cell proliferation, differentiation, tumorigenesis, and apoptosis. So far, no clear link has been established ...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/s41388-019-0789-3

    authors: Yang RM,Nanayakkara D,Kalimutho M,Mitra P,Khanna KK,Dray E,Gonda TJ

    更新日期:2019-06-01 00:00:00

  • siRNA screening identifies differences in the Fanconi anemia pathway in BALB/c-Trp53+/- with susceptibility versus C57BL/6-Trp53+/- mice with resistance to mammary tumors.

    abstract::BALB/c mice heterozygous for Trp53 develop a high proportion of spontaneous mammary tumors, a phenotype distinct from other mouse strains. BALB/c-Trp53+/- female mice, thus, resemble the hereditary Li-Fraumeni syndrome (LFS) characterized by early-onset of breast cancer, even though LFS involves TP53 mutations, which ...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2013.38

    authors: Böhringer M,Obermeier K,Griner N,Waldraff D,Dickinson E,Eirich K,Schindler D,Hagen M,Jerry DJ,Wiesmüller L

    更新日期:2013-11-28 00:00:00

  • Activation of NF-kappa B/Rel by Tax involves degradation of I kappa B alpha and is blocked by a proteasome inhibitor.

    abstract::The tax gene product of the human T-cell leukemia virus type I (HTLV-I) induces the nuclear expression and biological function of the NF-kappa B/Rel family of host transcription factors although the underlying mechanism remains unclear. In the present study, we demonstrate that Tax-mediated activation of NF-kappa B/Re...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:

    authors: Maggirwar SB,Harhaj E,Sun SC

    更新日期:1995-09-07 00:00:00