The E295K DNA polymerase beta gastric cancer-associated variant interferes with base excision repair and induces cellular transformation.

Abstract:

:Approximately 30% of human tumors examined for mutations in polymerase beta (pol beta) appear to express pol beta variant proteins (D. Starcevic, S. Dalal, and J. B. Sweasy, Cell Cycle 3:998-1001, 2004). Many of these variants result from a single amino acid substitution. We have previously shown that the K289M and I260M colon and prostate cancer variants, respectively, induce cellular transformation most likely due to sequence-specific mutator activity (S. Dalal et al., Biochemistry 44:15664-15673, 2005; T. Lang et al., Proc. Natl. Acad. Sci. USA 101:6074-6079, 2004; J. B. Sweasy et al., Proc. Natl. Acad. Sci. USA 102:14350-14355, 2005). In the work described here, we show that the E295K gastric carcinoma pol beta variant acts in a dominant-negative manner by interfering with base excision repair. This leads to an increase in sister chromatid exchanges. Expression of the E295K variant also induces cellular transformation. Our data suggest that unfilled gaps are channeled into a homology-directed repair pathway that could lead to genomic instability. The results indicate that base excision repair is critical for maintaining genome stability and could therefore be a tumor suppressor mechanism.

journal_name

Mol Cell Biol

authors

Lang T,Dalal S,Chikova A,DiMaio D,Sweasy JB

doi

10.1128/MCB.01883-06

subject

Has Abstract

pub_date

2007-08-01 00:00:00

pages

5587-96

issue

15

eissn

0270-7306

issn

1098-5549

pii

MCB.01883-06

journal_volume

27

pub_type

杂志文章
  • Mutant mouse models reveal the relative roles of E2F1 and E2F3 in vivo.

    abstract::The E2F1, -2, and -3 transcription factors are key downstream targets of the retinoblastoma protein (pRB) tumor suppressor that drive expression of proliferation-associated genes. Here we use mutant mouse strains to investigate E2F3's role in vivo. We show that E2F3 is essential for embryonic viability in the pure 129...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.22.8.2663-2672.2002

    authors: Cloud JE,Rogers C,Reza TL,Ziebold U,Stone JR,Picard MH,Caron AM,Bronson RT,Lees JA

    更新日期:2002-04-01 00:00:00

  • Targeted disruption of the idol gene alters cellular regulation of the low-density lipoprotein receptor by sterols and liver x receptor agonists.

    abstract::Previously, we identified the E3 ubiquitin ligase Idol (inducible degrader of the low-density lipoprotein [LDL] receptor [LDLR]) as a posttranscriptional regulator of the LDLR pathway. Idol stimulates LDLR degradation through ubiquitination of its C-terminal domain, thereby limiting cholesterol uptake. Here we report ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.01469-10

    authors: Scotti E,Hong C,Yoshinaga Y,Tu Y,Hu Y,Zelcer N,Boyadjian R,de Jong PJ,Young SG,Fong LG,Tontonoz P

    更新日期:2011-05-01 00:00:00

  • Critical role for a single leucine residue in leukemia induction by E2A-PBX1.

    abstract::In roughly 5% of cases of acute lymphoblastic leukemia, a chromosomal translocation leads to expression of the oncogenic protein E2A-PBX1. The N-terminal portion of E2A-PBX1, encoded by the E2A gene, is identical in sequence to the corresponding portion of the E proteins E12/E47 and includes transcriptional activation...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.02025-05

    authors: Bayly R,Murase T,Hyndman BD,Savage R,Nurmohamed S,Munro K,Casselman R,Smith SP,LeBrun DP

    更新日期:2006-09-01 00:00:00

  • Dual regulation of c-Myc by p300 via acetylation-dependent control of Myc protein turnover and coactivation of Myc-induced transcription.

    abstract::The c-Myc oncoprotein (Myc) controls cell fate by regulating gene transcription in association with a DNA-binding partner, Max. While Max lacks a transcription regulatory domain, the N terminus of Myc contains a transcription activation domain (TAD) that recruits cofactor complexes containing the histone acetyltransfe...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.25.23.10220-10234.2005

    authors: Faiola F,Liu X,Lo S,Pan S,Zhang K,Lymar E,Farina A,Martinez E

    更新日期:2005-12-01 00:00:00

  • Jun is phosphorylated by several protein kinases at the same sites that are modified in serum-stimulated fibroblasts.

    abstract::c-jun is a member of the family of immediate-early genes whose expression is induced by factors such as serum stimulation, phorbol ester, and differentiation signals. Here we show that increased Jun synthesis after serum stimulation is accompanied by a concomitant increase in phosphorylation. Several serine-threonine ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.12.10.4694

    authors: Baker SJ,Kerppola TK,Luk D,Vandenberg MT,Marshak DR,Curran T,Abate C

    更新日期:1992-10-01 00:00:00

  • Transposition of the yeast retroviruslike element Ty3 is dependent on the cell cycle.

    abstract::Host cell cycle genes provide important functions to retroviruses and retroviruslike elements. To define some of these functions, the cell cycle dependence of transposition of the yeast retroviruslike element Ty3 was examined. Ty3 is unique among retroviruslike elements because of the specificity of its integration, w...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.14.12.8229

    authors: Menees TM,Sandmeyer SB

    更新日期:1994-12-01 00:00:00

  • Expression of the Aplysia californica rho gene in Escherichia coli: purification and characterization of its encoded p21 product.

    abstract::A new family of highly conserved genes, designated rho, has recently been isolated and characterized (P. Madaule and R. Axel, Cell 41:31-40, 1985). These genes have been found in Saccharomyces cerevisiae, Drosophila melanogaster, rats, and humans, and their 21,000-dalton products are highly homologous. The rho p21 pro...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.7.10.3620

    authors: Anderson PS,Lacal JC

    更新日期:1987-10-01 00:00:00

  • The hnRNA-binding proteins hnRNP L and PTB are required for efficient translation of the Cat-1 arginine/lysine transporter mRNA during amino acid starvation.

    abstract::The response to amino acid starvation involves the global decrease of protein synthesis and an increase in the translation of some mRNAs that contain an internal ribosome entry site (IRES). It was previously shown that translation of the mRNA for the arginine/lysine amino acid transporter Cat-1 increases during amino ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.01774-08

    authors: Majumder M,Yaman I,Gaccioli F,Zeenko VV,Wang C,Caprara MG,Venema RC,Komar AA,Snider MD,Hatzoglou M

    更新日期:2009-05-01 00:00:00

  • Interaction of p53 with its consensus DNA-binding site.

    abstract::We have analyzed the specific interaction of murine p53 with the consensus DNA-binding sequence 5'-AGACATGCCT-AGACATGCCT-3'. We used segments of p53 lacking the C-terminal, nonspecific DNA-binding domain because the presence of an autonomous nonspecific DNA-binding domain in wild-type p53 would complicate analysis of ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.15.4.2157

    authors: Wang Y,Schwedes JF,Parks D,Mann K,Tegtmeyer P

    更新日期:1995-04-01 00:00:00

  • Guanine nucleotide activation of, and competition between, RAS proteins from Saccharomyces cerevisiae.

    abstract::In the yeast Saccharomyces cerevisiae, yeast RAS proteins are potent activators of adenylate cyclase. In the present work we measured the activity of adenylate cyclase in membranes from Saccharomyces cerevisiae which overexpress this enzyme. The response of the enzyme to added RAS2 proteins bound with various guanine ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.7.6.2128

    authors: Field J,Broek D,Kataoka T,Wigler M

    更新日期:1987-06-01 00:00:00

  • Generation of a variant t(2;8) translocation of Burkitt's lymphoma by site-specific recombination via the kappa light-chain joining signals.

    abstract::We analyzed the Burkitt's lymphoma line BL64 in which a reciprocal translocation joins the immunoglobulin kappa light-chain locus on chromosome 2 to the c-myc gene on chromosome 8. The breakpoints on the two marker chromosomes 8+ and 2p- occurred 5' of the Js segment within the conserved nonamer and heptamer recombina...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.7.6.2037

    authors: Hartl P,Lipp M

    更新日期:1987-06-01 00:00:00

  • Anaplastic lymphoma kinase is a dependence receptor whose proapoptotic functions are activated by caspase cleavage.

    abstract::Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase, initially discovered as part of the NPM-ALK fusion protein, resulting from the t(2;5) translocation that is frequently associated with anaplastic large-cell lymphomas. The native ALK protein is normally expressed in the developing and, at a weaker level, ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.01515-05

    authors: Mourali J,Bénard A,Lourenço FC,Monnet C,Greenland C,Moog-Lutz C,Racaud-Sultan C,Gonzalez-Dunia D,Vigny M,Mehlen P,Delsol G,Allouche M

    更新日期:2006-08-01 00:00:00

  • trans-spliceosomal U6 RNAs of Crithidia fasciculata and Leptomonas seymouri: deviation from the conserved ACAGAG sequence and potential base pairing with spliced leader RNA.

    abstract::U6 RNA genes from the trypanosomatids Crithidia fasciculata and Leptomonas seymouri have been isolated and sequenced. As in Trypanosoma brucei, the U6 RNA genes in both C. fasciculata and L. seymouri are arranged in close linkage with upstream tRNA genes. The U6 RNA sequences from C. fasciculata and L. seymouri deviat...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.14.7.4565

    authors: Xu GL,Wieland B,Bindereif A

    更新日期:1994-07-01 00:00:00

  • Ki-67 Contributes to Normal Cell Cycle Progression and Inactive X Heterochromatin in p21 Checkpoint-Proficient Human Cells.

    abstract::The Ki-67 protein is widely used as a tumor proliferation marker. However, whether Ki-67 affects cell cycle progression has been controversial. Here we demonstrate that depletion of Ki-67 in human hTERT-RPE1, WI-38, IMR90, and hTERT-BJ cell lines and primary fibroblast cells slowed entry into S phase and coordinately ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.00569-16

    authors: Sun X,Bizhanova A,Matheson TD,Yu J,Zhu LJ,Kaufman PD

    更新日期:2017-08-11 00:00:00

  • E2F3 loss has opposing effects on different pRB-deficient tumors, resulting in suppression of pituitary tumors but metastasis of medullary thyroid carcinomas.

    abstract::The E2F transcription factors are key downstream targets of the retinoblastoma protein (pRB) tumor suppressor. We have previously shown that E2F3 plays a critical role in mediating the mitogen-induced activation of E2F-responsive genes and contributes to both the inappropriate proliferation and the p53-dependent apopt...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.23.18.6542-6552.2003

    authors: Ziebold U,Lee EY,Bronson RT,Lees JA

    更新日期:2003-09-01 00:00:00

  • Differential interactions of specific nuclear factor I isoforms with the glucocorticoid receptor and STAT5 in the cooperative regulation of WAP gene transcription.

    abstract::The distal region (-830 to -720 bp) of the rat whey acidic protein (WAP) gene contains a composite response element (CoRE), which has been demonstrated previously to confer mammary gland-specific and hormonally regulated WAP gene expression. Point mutations in the binding sites for specific transcription factors prese...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.21.20.6859-6869.2001

    authors: Mukhopadhyay SS,Wyszomierski SL,Gronostajski RM,Rosen JM

    更新日期:2001-10-01 00:00:00

  • Mitosis-specific phosphorylation of nucleolin by p34cdc2 protein kinase.

    abstract::Nucleolin is a ubiquitous multifunctional protein involved in preribosome assembly and associated with both nucleolar chromatin in interphase and nucleolar organizer regions on metaphasic chromosomes in mitosis. Extensive nucleolin phosphorylation by a casein kinase (CKII) occurs on serine in growing cells. Here we re...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.10.7.3607

    authors: Belenguer P,Caizergues-Ferrer M,Labbé JC,Dorée M,Amalric F

    更新日期:1990-07-01 00:00:00

  • A palindromic regulatory site within vertebrate GATA-1 promoters requires both zinc fingers of the GATA-1 DNA-binding domain for high-affinity interaction.

    abstract::GATA-1, a transcription factor essential for the development of the erythroid lineage, contains two adjacent highly conserved zinc finger motifs. The carboxy-terminal finger is necessary and sufficient for specific binding to the consensus GATA recognition sequence: mutant proteins containing only the amino-terminal f...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.16.5.2238

    authors: Trainor CD,Omichinski JG,Vandergon TL,Gronenborn AM,Clore GM,Felsenfeld G

    更新日期:1996-05-01 00:00:00

  • Sedimentation analysis of polyadenylation-specific complexes.

    abstract::Precursor RNA containing the adenovirus L3 polyadenylation site is assembled into a 50S complex upon incubation with HeLa nuclear extract at 30 degrees C. The cofactor and sequence requirements for 50S complex formation are similar to those of the in vitro polyadenylation reaction. Assembly of this complex requires AT...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.8.1.226

    authors: Moore CL,Skolnik-David H,Sharp PA

    更新日期:1988-01-01 00:00:00

  • Transcriptional activation of the human epidermal growth factor receptor promoter by human p53.

    abstract::The human epidermal growth factor receptor (EGFR) promoter is activated by both wild-type and tumor-derived mutant p53. In this communication, we demonstrate that EGFR promoter sequence requirements for transactivation by wild-type and mutant p53 are different. Transient-expression assays with EGFR promoter deletions ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.16.11.6009

    authors: Ludes-Meyers JH,Subler MA,Shivakumar CV,Munoz RM,Jiang P,Bigger JE,Brown DR,Deb SP,Deb S

    更新日期:1996-11-01 00:00:00

  • Monoubiquitination of Cancer Stem Cell Marker CD133 at Lysine 848 Regulates Its Secretion and Promotes Cell Migration.

    abstract::CD133, a widely known marker of cancer stem cells, was recently found in extracellular vesicles. However, the mechanisms underlying CD133 translocation to the extracellular space remain largely unknown. Here we report that CD133 is monoubiquitinated. Ubiquitination occurs primarily on complex glycosylated CD133. The l...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.00024-18

    authors: Yang F,Xing Y,Li Y,Chen X,Jiang J,Ai Z,Wei Y

    更新日期:2018-07-16 00:00:00

  • Characterization of a family of related cellular transcription factors which can modulate human immunodeficiency virus type 1 transcription in vitro.

    abstract::LBP-1 is a cellular protein which binds strongly to sequences around the human immunodeficiency virus type 1 (HIV-1) initiation site and weakly over the TATA box. We have previously shown that LBP-1 represses HIV-1 transcription by inhibiting the binding of TFIID to the TATA box. Four similar but distinct cDNAs encodi...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.14.3.1776

    authors: Yoon JB,Li G,Roeder RG

    更新日期:1994-03-01 00:00:00

  • A genetic analysis of the E2F1 gene distinguishes regulation by Rb, p107, and adenovirus E4.

    abstract::The cellular transcription factor E2F appears to be a target for the regulatory action of the retinoblastoma tumor suppressor gene product. The recent isolation of the E2F1 cDNA clone, which encodes a polypeptide with properties characteristic of E2F, has now allowed a more detailed analysis of the regulation of E2F f...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.13.10.6314

    authors: Cress WD,Johnson DG,Nevins JR

    更新日期:1993-10-01 00:00:00

  • c-myc Internal ribosome entry site activity is developmentally controlled and subjected to a strong translational repression in adult transgenic mice.

    abstract::The expression of c-myc proto-oncogene, a key regulator of cell proliferation and apoptosis, is controlled at different transcriptional and posttranscriptional levels. In particular, the c-myc mRNA contains an internal ribosome entry site (IRES) able to promote translation initiation independently from the classical c...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.21.5.1833-1840.2001

    authors: Créancier L,Mercier P,Prats AC,Morello D

    更新日期:2001-03-01 00:00:00

  • Multiple cis-acting sequence elements are required for efficient splicing of simian virus 40 small-t antigen pre-mRNA.

    abstract::We have determined the effects of a number of mutations in the small-t antigen mRNA intron on the alternative splicing pattern of the simian virus 40 early transcript. Expansion of the distance separating the small-t pre-mRNA lariat branch point and the shared large T-small t 3' splice site from 18 to 29 nucleotides (...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.8.9.3582

    authors: Fu XY,Colgan JD,Manley JL

    更新日期:1988-09-01 00:00:00

  • Induction of RNA editing at heterologous sites by sequences in apolipoprotein B mRNA.

    abstract::An RNA editing mechanism modifies apolipoprotein B (apo-B) mRNA in the intestine by converting cytosine at nucleotide (nt) 6666 to uracil. To define the sequence requirements for editing, mutant apo-B RNAs were analyzed for the ability to be edited in vitro by enterocyte extracts. Editing was detected by a sensitive a...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.13.12.7288

    authors: Driscoll DM,Lakhe-Reddy S,Oleksa LM,Martinez D

    更新日期:1993-12-01 00:00:00

  • Effects of rho kinase and actin stress fibers on sustained extracellular signal-regulated kinase activity and activation of G(1) phase cyclin-dependent kinases.

    abstract::We recently reported that Rho kinase is required for sustained ERK signaling and the consequent mid-G(1) phase induction of cyclin D1 in fibroblasts. The results presented here indicate that these Rho kinase effects are mediated by the formation of stress fibers and the consequent clustering of alpha5beta1 integrin. M...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章,收录出版

    doi:10.1128/mcb.23.12.4283-4294.2003

    authors: Roovers K,Assoian RK

    更新日期:2003-06-01 00:00:00

  • Posttranscriptional regulation of chicken ccn2 gene expression by nucleophosmin/B23 during chondrocyte differentiation.

    abstract::CCN2/CTGF is a multifunctional factor that plays a crucial role in the growth and differentiation of chondrocytes. The chicken ccn2 gene is regulated not only at the transcriptional level but also by the interaction between a posttranscriptional element in the 3' untranslated region (3'-UTR) and a cofactor. In the pre...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.00495-08

    authors: Mukudai Y,Kubota S,Kawaki H,Kondo S,Eguchi T,Sumiyoshi K,Ohgawara T,Shimo T,Takigawa M

    更新日期:2008-10-01 00:00:00

  • Differential DNA binding by monomeric, homodimeric, and potentially heteromeric forms of the thyroid hormone receptor.

    abstract::Binding of the thyroid hormone receptor (TR) to thyroid hormone-responsive elements (TREs) is crucial for regulation of gene expression by thyroid hormone. The TR binds to each half-site of a palindromic TRE separately, as a monomer, or simultaneously, as a homodimer. In addition, the TR monomer interacts with a 42-kD...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.11.10.5005

    authors: Lazar MA,Berrodin TJ,Harding HP

    更新日期:1991-10-01 00:00:00

  • Salmonella Engages Host MicroRNAs To Modulate SUMOylation: a New Arsenal for Intracellular Survival.

    abstract::Posttranslational modifications (PTMs) can alter many fundamental properties of a protein. One or combinations of them have been known to regulate the dynamics of many cellular pathways and consequently regulate all vital processes. Understandably, pathogens have evolved sophisticated strategies to subvert these mecha...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.00397-15

    authors: Verma S,Mohapatra G,Ahmad SM,Rana S,Jain S,Khalsa JK,Srikanth CV

    更新日期:2015-09-01 00:00:00