Literature DB >> 2136708

The state of cellular differentiation determines the activity of the adenovirus E1A enhancer element: evidence for negative regulation of enhancer function.

R S Herbst1, M Pelletier, E M Boczko, L E Babiss.   

Abstract

Most of the eucaryotic enhancer elements so far described consist of multiple DNA binding sites for proteins that act either synergistically or antagonistically to modulate the rate of transcription. In this report, we show that the activity of the adenovirus E1A enhancer element is suppressed in virus-infected undifferentiated rodent fetal fibroblast cells (CREF and F111 cells) and primary rat liver hepatocytes that have lost their fully differentiated phenotype (dedifferentiated). This contrasts with the results obtained for virus-infected differentiated or partially dedifferentiated rodent hepatocytes or hepatoma cell lines and human HeLa cells, in which deletion of the E1A enhancer domain greatly reduces the rate of E1A gene transcription. An in vitro quantitation of the nuclear proteins (from HeLa and CREF cells) that interact with and modulate the activity of the E1A enhancer revealed similar binding activities for the E2f and ATF proteins. However, an AP3-like (phi AP3) activity was present at a 10- to 20-fold higher concentration in CREF cells than in HeLa cells, and removal of this phi AP3-binding site on the viral genome resulted in an increase in the rate of E1A gene transcription in virus-infected CREF cells. Together, these results demonstrated that the factors which positively regulate enhancer function were present in CREF cells and that the phi AP3 factor was acting to suppress the activity of the E1A enhancer. Furthermore, the level of this factor was found to increase to even higher levels in CREF cells treated with 12-O-tetradecanoylphorbol-13-acetate, and this induction resulted in a further suppression in the rate of E1A gene transcription. On the basis of these observations, we propose that E1A expression is negatively regulated by the phi AP3 factor in undifferentiated rodent fetal fibroblast cells and that this could be an important mechanism that distinguishes between establishment of the differentiated cell versus transformed cell phenotypes.

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Year:  1990        PMID: 2136708      PMCID: PMC249075     

Source DB:  PubMed          Journal:  J Virol        ISSN: 0022-538X            Impact factor:   5.103


  62 in total

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Journal:  Cell       Date:  1977-04       Impact factor: 41.582

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Journal:  Cell       Date:  1986-04-25       Impact factor: 41.582

Review 4.  Trans-acting protein factors and the regulation of eukaryotic transcription: lessons from studies on DNA tumor viruses.

Authors:  N C Jones; P W Rigby; E B Ziff
Journal:  Genes Dev       Date:  1988-03       Impact factor: 11.361

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Authors:  B Ondek; L Gloss; W Herr
Journal:  Nature       Date:  1988-05-05       Impact factor: 49.962

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Journal:  Nucleic Acids Res       Date:  1988-04-11       Impact factor: 16.971

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Authors:  L A Chodosh; A S Baldwin; R W Carthew; P A Sharp
Journal:  Cell       Date:  1988-04-08       Impact factor: 41.582

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Journal:  Nucleic Acids Res       Date:  1980-01-11       Impact factor: 16.971

9.  5-Bromo-2'-deoxyuridine potentiation of transformation of rat-embryo cells induced in vitro by 3-methylcholanthrene: induction of rat leukemia virus gs antigen in transformed cells.

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Journal:  Proc Natl Acad Sci U S A       Date:  1973-08       Impact factor: 11.205

10.  A liver-specific DNA-binding protein recognizes multiple nucleotide sites in regulatory regions of transthyretin, alpha 1-antitrypsin, albumin, and simian virus 40 genes.

Authors:  R H Costa; D R Grayson; K G Xanthopoulos; J E Darnell
Journal:  Proc Natl Acad Sci U S A       Date:  1988-06       Impact factor: 11.205

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  10 in total

1.  pRB binds to and modulates the transrepressing activity of the E1A-regulated transcription factor p120E4F.

Authors:  L Fajas; C Paul; O Zugasti; L Le Cam; J Polanowska; E Fabbrizio; R Medema; M L Vignais; C Sardet
Journal:  Proc Natl Acad Sci U S A       Date:  2000-07-05       Impact factor: 11.205

2.  The efficiency of adenovirus transformation of rodent cells is inversely related to the rate of viral E1A gene expression.

Authors:  G R Adami; L E Babiss
Journal:  J Virol       Date:  1990-07       Impact factor: 5.103

3.  Human papillomavirus E6E7-mediated adenovirus cell killing: selectivity of mutant adenovirus replication in organotypic cultures of human keratinocytes.

Authors:  C Balagué; F Noya; R Alemany; L T Chow; D T Curiel
Journal:  J Virol       Date:  2001-08       Impact factor: 5.103

4.  Comparison between E1A gene from oncogenic and non-oncogenic adenoviruses in cellular transformation (Ad E1A conserved region).

Authors:  V Leclére; I Huvent; P Verwaerde; C Cousin; J C D'Halluin
Journal:  Arch Virol       Date:  1993       Impact factor: 2.574

5.  Induced expression of the endogenous beta interferon gene in adenovirus type 5-transformed rat fibroblasts.

Authors:  U Nielsch; R Pine; S G Zimmer; L E Babiss
Journal:  J Virol       Date:  1992-04       Impact factor: 5.103

6.  p21 Promotes oncolytic adenoviral activity in ovarian cancer and is a potential biomarker.

Authors:  Magdalena B Flak; Claire M Connell; Claude Chelala; Kyra Archibald; Michael A Salako; Katrina J Pirlo; Michelle Lockley; Sally P Wheatley; Frances R Balkwill; Iain A McNeish
Journal:  Mol Cancer       Date:  2010-07-03       Impact factor: 27.401

7.  Regulation of a human cytomegalovirus immediate-early gene (US3) by a silencer-enhancer combination.

Authors:  A R Thrower; G C Bullock; J E Bissell; M F Stinski
Journal:  J Virol       Date:  1996-01       Impact factor: 5.103

8.  Activation of adenovirus early promoters and lytic phase in differentiated strata of organotypic cultures of human keratinocytes.

Authors:  Francisco Noya; Cristina Balagué; N Sanjib Banerjee; David T Curiel; Thomas R Broker; Louise T Chow
Journal:  J Virol       Date:  2003-06       Impact factor: 5.103

9.  Repression of adenovirus E1A enhancer activity by a novel zinc finger-containing DNA-binding protein related to the GLI-Kruppel protein.

Authors:  C Fognani; G Della Valle; L E Babiss
Journal:  EMBO J       Date:  1993-12-15       Impact factor: 11.598

10.  Changes in NF-kappa B and ISGF3 DNA binding activities are responsible for differences in MHC and beta-IFN gene expression in Ad5- versus Ad12-transformed cells.

Authors:  U Nielsch; S G Zimmer; L E Babiss
Journal:  EMBO J       Date:  1991-12       Impact factor: 11.598

  10 in total

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