A functional analysis of PCNA-binding peptides derived from protein sequence, interaction screening and rational design.

Abstract:

:Proliferating cell nuclear antigen (PCNA) has no intrinsic enzymatic function, but functions as a sliding platform to mediate protein interactions with the DNA strand. Many proteins interact with PCNA through a small conserved motif with consensus QxxLxxFF. This work uses Schizosaccharomyces pombe and human cells to analyse the function of PCNA-binding peptides. Interacting peptides were identified using two-hybrid screening; one (pep102) binds directly to a physiologically relevant site on PCNA. The EGFP-pep102 overexpression phenotype is consistent with competitive blocking of PCNA-protein interactions. Various PCNA-binding peptides were all shown to inhibit PCNA function by competitive binding in both human and S. pombe cells as EGFP fusion proteins. The action of a p21(WAF1/Cip1)-derived peptide was complicated by the presence of additional functional domains and possible post-translational modification. The activity of pep102 was hampered by low expression in both model systems. The peptide derived from rational design (con1) was stable, highly active in inhibiting PCNA function both S. pombe and human cells and showed a high affinity for PCNA both in vitro and in vivo. These results validate the use of functional screening in yeast to identify peptide aptamers that are functional in mammalian cells; such aptamers provide excellent leads for small molecule antiproliferative therapies.

journal_name

Oncogene

journal_title

Oncogene

authors

Warbrick E

doi

10.1038/sj.onc.1209320

subject

Has Abstract

pub_date

2006-05-11 00:00:00

pages

2850-9

issue

20

eissn

0950-9232

issn

1476-5594

pii

1209320

journal_volume

25

pub_type

杂志文章

相关文献

ONCOGENE文献大全
  • Melanoma metastasis: new concepts and evolving paradigms.

    abstract::Melanoma progression is typically depicted as a linear and stepwise process in which metastasis occurs relatively late in disease progression. Significant evidence suggests that in a subset of melanomas, progression is much more complex and less linear in nature. Epidemiologic and experimental observations in melanoma...

    journal_title:Oncogene

    pub_type: 杂志文章,评审

    doi:10.1038/onc.2013.194

    authors: Damsky WE,Theodosakis N,Bosenberg M

    更新日期:2014-05-08 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

  • p53/BNIP3-dependent mitophagy limits glycolytic shift in radioresistant cancer.

    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

    authors: Chang HW,Kim MR,Lee HJ,Lee HM,Kim GC,Lee YS,Nam HY,Lee M,Jang HJ,Lee KE,Lee JC,Byun Y,Kim SW,Kim SY

    更新日期:2019-05-01 00:00:00

  • Detailed analysis of the basic domain of the E2F1 transcription factor indicates that it is unique among bHLH proteins.

    abstract::The E2F1 transcription factor binds to sites within the promoters of a number of cell cycle regulated genes through a basic-helix-loop-helix motif (bHLH). It is shown here that the basic region of E2F1 is distinct from that of all other bHLH proteins. The center of the basic region contains a helix breaking proline-gl...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:

    authors: Jordan KL,Haas AR,Logan TJ,Hall DJ

    更新日期:1994-04-01 00:00:00

  • Deregulated expression of E2F-1 induces cyclin A- and E-associated kinase activities independently from cell cycle position.

    abstract::The transcription factor E2F activates genes required for S phase, such as cyclin E and cyclin A. We show that, contrary to long term effects of E2F-1 overexpression, short ectopic overexpression of this transcription factor in logarithmically growing cells does neither affect the cell cycle distribution nor the cell ...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1201061

    authors: Soucek T,Pusch O,Hengstschläger-Ottnad E,Adams PD,Hengstschläger M

    更新日期:1997-05-15 00:00:00

  • Rad54 and Mus81 cooperation promotes DNA damage repair and restrains chromosome missegregation.

    abstract::Rad54 and Mus81 mammalian proteins physically interact and are important for the homologous recombination DNA repair pathway; however, their functional interactions in vivo are poorly defined. Here, we show that combinatorial loss of Rad54 and Mus81 results in hypersensitivity to DNA-damaging agents, defects on both t...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2016.16

    authors: Ghamrasni SE,Cardoso R,Li L,Guturi KK,Bjerregaard VA,Liu Y,Venkatesan S,Hande MP,Henderson JT,Sanchez O,Hickson ID,Hakem A,Hakem R

    更新日期:2016-09-15 00:00:00

  • IL-4 regulation of IL-6 production involves Rac/Cdc42- and p38 MAPK-dependent pathways in keratinocytes.

    abstract::The stress-activated pathways leading to activation of p38 MAP kinase (p38 MAPK) and c-jun N-terminal kinases (JNK) have been shown to be activated by pro-inflammatory cytokines, physical and chemical stresses as well as a variety of hematopoietic growth factors. One exception is interleukin (IL)-4, which does not act...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1203458

    authors: Wery-Zennaro S,Zugaza JL,Letourneur M,Bertoglio J,Pierre J

    更新日期:2000-03-16 00:00:00

  • Oxidative metabolism, gap junctions and the ionizing radiation-induced bystander effect.

    abstract::Evidence accumulated over the past two decades has indicated that exposure of cell populations to ionizing radiation results in significant biological effects occurring in both the irradiated and nonirradiated cells in the population. This phenomenon, termed the 'bystander response', has been shown to occur both in vi...

    journal_title:Oncogene

    pub_type: 杂志文章,评审

    doi:10.1038/sj.onc.1206961

    authors: Azzam EI,de Toledo SM,Little JB

    更新日期:2003-10-13 00:00:00

  • Association of RACK1 and PKCbeta with the common beta-chain of the IL-5/IL-3/GM-CSF receptor.

    abstract::Granulocyte macrophage colony stimulating factor (GM-CSF), interleukin-3 (IL-3) and interleukin-5 (IL-5 belong to a family of cytokines that regulate proliferation, differentiation and function of haematopoietic cells. Their receptor consists of a ligand specific alpha-chain and a signal transducing beta-chain (betac)...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1202896

    authors: Geijsen N,Spaargaren M,Raaijmakers JA,Lammers JW,Koenderman L,Coffer PJ

    更新日期:1999-09-09 00:00:00

  • Murine WNT11 is a secreted glycoprotein that morphologically transforms mammary epithelial cells.

    abstract::Wnt genes encode a set of structurally related cell surface glycoproteins that appear to have roles in cell-cell signalling. The ectopic expression of several murine Wnt genes has been implicated in the transformation of mammary epithelial and the onset of mammary tumours. Wnt11 is expressed in the developing embryo i...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:

    authors: Christiansen JH,Monkley SJ,Wainwright BJ

    更新日期:1996-06-20 00:00:00

  • Antibody targeting of anaplastic lymphoma kinase induces cytotoxicity of human neuroblastoma.

    abstract::Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase aberrantly expressed in neuroblastoma, a devastating pediatric cancer of the sympathetic nervous system. Germline and somatically acquired ALK aberrations induce increased autophosphorylation, constitutive ALK activation and increased downstream signaling....

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2011.647

    authors: Carpenter EL,Haglund EA,Mace EM,Deng D,Martinez D,Wood AC,Chow AK,Weiser DA,Belcastro LT,Winter C,Bresler SC,Vigny M,Mazot P,Asgharzadeh S,Seeger RC,Zhao H,Guo R,Christensen JG,Orange JS,Pawel BR,Lemmon MA,Mossé

    更新日期:2012-11-15 00:00:00

  • MicroRNA-377 suppresses initiation and progression of esophageal cancer by inhibiting CD133 and VEGF.

    abstract::Esophageal cancer is one of the most lethal cancers worldwide with poor survival and limited therapeutic options. The discovery of microRNAs created a new milestone in cancer research. miR-377 is located in chromosome region 14q32, which is frequently deleted in esophageal squamous cell carcinoma (ESCC), but the biolo...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2017.29

    authors: Li B,Xu WW,Han L,Chan KT,Tsao SW,Lee NPY,Law S,Xu LY,Li EM,Chan KW,Qin YR,Guan XY,He QY,Cheung ALM

    更新日期:2017-07-13 00:00:00

  • TRIB3 confers radiotherapy resistance in esophageal squamous cell carcinoma by stabilizing TAZ.

    abstract::Radioresistance becomes the major obstacle to reduce tumor recurrence and improve prognosis in the treatment of esophageal squamous cell carcinoma (ESCC). Thus new strategies for radioresistant ESCC are urgently needed. Herein, we reported that tribbles pseudokinase 3 (TRIB3) serves as a key regulator of radioresistan...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/s41388-020-1245-0

    authors: Zhou S,Liu S,Lin C,Li Y,Ye L,Wu X,Jian Y,Dai Y,Ouyang Y,Zhao L,Liu M,Song L,Xi M

    更新日期:2020-04-01 00:00:00

  • Functional inactivation of Cdk9 through oligomerization chain reaction.

    abstract::The oligomerization chain reaction (OCR) strategy is a recently described technique for inactivation of target proteins that function as homoassociate complexes. This novel strategy is based on the fusion of self-associating coiled-coil (CC) domain of the nuclear factor promyelocytic leukemia (PML) to target proteins....

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1206785

    authors: Napolitano G,Mazzocco A,Fraldi A,Majello B,Lania L

    更新日期:2003-07-31 00:00:00

  • The β-catenin/TCF-4-LINC01278-miR-1258-Smad2/3 axis promotes hepatocellular carcinoma metastasis.

    abstract::Hepatocellular carcinoma (HCC) metastasis is largely responsible for HCC-associated recurrence and mortality. We aimed to identify metastasis-related long non-coding RNAs (lncRNAs) to understand the molecular mechanism of HCC metastasis. We first identified that miR-1258 was downregulated in HCC tissues both in The Ca...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/s41388-020-1307-3

    authors: Huang WJ,Tian XP,Bi SX,Zhang SR,He TS,Song LY,Yun JP,Zhou ZG,Yu RM,Li M

    更新日期:2020-06-01 00:00:00

  • Studying the pathogenesis of BCR-ABL+ leukemia in mice.

    abstract::Animal models of BCR-ABL+ leukemias have provided important new knowledge about the molecular pathophysiology of these diseases, and answered questions that are difficult or impossible to address using BCR-ABL-expressing cell lines or primary Ph+ leukemia samples from patients. The power of mouse models lies in their ...

    journal_title:Oncogene

    pub_type: 杂志文章,评审

    doi:10.1038/sj.onc.1206091

    authors: Van Etten RA

    更新日期:2002-12-09 00:00:00

  • Kinase activity-independent suppression of p73alpha by AMP-activated kinase alpha (AMPKalpha).

    abstract::Although p73alpha induces many of the same cellular events as p53, it is structurally distinct from p53 in that it possesses a unique COOH-terminal domain. To dissect the function of this domain, we performed yeast two-hybrid screening of a HeLa cDNA library using residues 552-636 of p73alpha as bait. Among the clones...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2008.452

    authors: Lee YG,Lee SW,Sin HS,Kim EJ,Um SJ

    更新日期:2009-02-19 00:00:00

  • Akt inhibitor A-443654 induces rapid Akt Ser-473 phosphorylation independent of mTORC1 inhibition.

    abstract::Rapamycin, a natural product inhibitor of the Raptor-mammalian target of rapamycin complex (mTORC1), is known to induce Protein kinase B (Akt/PKB) Ser-473 phosphorylation in a subset of human cancer cell lines through inactivation of S6K1, stabilization of insulin receptor substrate (IRS)-1, and increased signaling th...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1210343

    authors: Han EK,Leverson JD,McGonigal T,Shah OJ,Woods KW,Hunter T,Giranda VL,Luo Y

    更新日期:2007-08-16 00:00:00

  • The non-catalytic domain of ras-GAP inhibits transformation induced by G protein coupled receptors.

    abstract::We have studied the relationship between ras-GAP and G protein coupled receptors in a proliferative setting comprised of NIH3T3 expressing transfected muscarinic receptors (mAChRs). GAP expression plasmids were engineered to encode wild-type GAP, its carboxyl-terminal catalytic domain, a mutant lacking a portion of th...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:

    authors: Xu N,McCormick F,Gutkind JS

    更新日期:1994-02-01 00:00:00

  • AP2α controls the dynamic balance between miR-126&126* and miR-221&222 during melanoma progression.

    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

    authors: Felli N,Errico MC,Pedini F,Petrini M,Puglisi R,Bellenghi M,Boe A,Felicetti F,Mattia G,De Feo A,Bottero L,Tripodo C,Carè A

    更新日期:2016-06-09 00:00:00

  • Frequent loss of heterozygosity on chromosome 14 occurs in advanced colorectal carcinomas.

    abstract::The current model for colorectal tumorigenesis defines four specific mutations (activation of a ras proto-oncogene and inactivation of the APC, p53 and DCC tumor-suppressor genes) that accumulate in a colonic epithelial cell as it progresses towards a carcinoma. However, further mutations must be needed for progressio...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:

    authors: Young J,Leggett B,Ward M,Thomas L,Buttenshaw R,Searle J,Chenevix-Trench G

    更新日期:1993-03-01 00:00:00

  • Chromatin structure of the regulatory regions of pS2 and cathepsin D genes in hormone-dependent and -independent breast cancer cell lines.

    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

    authors: Giamarchi C,Solanas M,Chailleux C,Augereau P,Vignon F,Rochefort H,Richard-Foy H

    更新日期:1999-01-14 00:00:00

  • TIPUH1 encodes a novel KRAB zinc-finger protein highly expressed in human hepatocellular carcinomas.

    abstract::To achieve a better understanding of mechanisms that underlie hepatocarcinogenesis and to identify novel target molecules for diagnosis and therapy of hepatocellular carcinoma (HCC), we previously analysed gene-expression profiles of 20 HCC tissues on a cDNA microarray. Among the genes upregulated in the tumor tissues...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1209517

    authors: Silva FP,Hamamoto R,Furukawa Y,Nakamura Y

    更新日期:2006-08-17 00:00:00

  • LOT1 is a growth suppressor gene down-regulated by the epidermal growth factor receptor ligands and encodes a nuclear zinc-finger protein.

    abstract::We previously reported cloning the rLot1 gene, and its human homolog (hLOT1), through analysis of differential gene expression in normal and malignant rat ovarian surface epithelial cells. Both human and rat ovarian carcinoma cell lines exhibited lost or decreased expression of this gene. Interestingly, the LOT1 gene ...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1203067

    authors: Abdollahi A,Bao R,Hamilton TC

    更新日期:1999-11-11 00:00:00

  • BS69, an adenovirus E1A-associated protein, inhibits the transcriptional activity of c-Myb.

    abstract::The carboxyl terminus of c-Myb contains a negative regulatory domain that is absent in the v-Myb oncoprotein, but conserved among all the known Myb proteins of animals. This domain inhibits transcriptional activation by c-Myb in animal cells, but not in budding yeast, suggesting that additional protein(s) present in a...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1204048

    authors: Ladendorff NE,Wu S,Lipsick JS

    更新日期:2001-01-04 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

  • Glycolysis gatekeeper PDK1 reprograms breast cancer stem cells under hypoxia.

    abstract::Glycolysis is critical for cancer stem cell reprogramming; however, the underlying regulatory mechanisms remain elusive. Here, we show that pyruvate dehydrogenase kinase 1 (PDK1) is enriched in breast cancer stem cells (BCSCs), whereas depletion of PDK1 remarkably diminishes ALDH+ subpopulations, decreases stemness-re...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2017.368

    authors: Peng F,Wang JH,Fan WJ,Meng YT,Li MM,Li TT,Cui B,Wang HF,Zhao Y,An F,Guo T,Liu XF,Zhang L,Lv L,Lv DK,Xu LZ,Xie JJ,Lin WX,Lam EW,Xu J,Liu Q

    更新日期:2018-02-22 00:00:00

  • Stabilization of prolactin receptor in breast cancer cells.

    abstract::The role of the hormone prolactin (PRL) in the pathogenesis of breast cancer is mediated by its cognate receptor (PRLr). Ubiquitin-dependent degradation of the PRLr that negatively regulates PRL signaling is triggered by PRL-mediated phosphorylation of PRLr on Ser349 followed by the recruitment of the beta-transducin ...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1209214

    authors: Li Y,Clevenger CV,Minkovsky N,Kumar KG,Raghunath PN,Tomaszewski JE,Spiegelman VS,Fuchs SY

    更新日期:2006-03-23 00:00:00

  • Canonical WNT signalling determines lineage specificity in Wilms tumour.

    abstract::Wilms tumours (WTs) have two distinct types of histology with or without ectopic mesenchymal elements, suggesting that WTs arise from either the mesenchymal or epithelial nephrogenic lineages. Regardless of the presence or absence of CTNNB1 mutations, nuclear accumulation of beta-catenin is often observed in WTs with ...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2008.455

    authors: Fukuzawa R,Anaka MR,Weeks RJ,Morison IM,Reeve AE

    更新日期:2009-02-26 00:00:00

  • Activation of p53 by roscovitine-mediated suppression of MDM2 expression.

    abstract::The p53 tumor suppressor is regulated by the MDM2 oncoprotein. Overexpression of MDM2 maintains p53 at low levels and contributes to the functional inactivation of p53 in a subset of tumors. We found that treatment with roscovitine and olomoucin, which were originally developed as cyclin-dependent kinase (CDK) inhibit...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1204412

    authors: Lu W,Chen L,Peng Y,Chen J

    更新日期:2001-05-31 00:00:00