A transcriptional repressor encoded by BPV-1 shares a common carboxy-terminal domain with the E2 transactivator

Lambert, Paul F.; Spalholz, Barbara A.; Howley, Peter M.

doi:10.1016/0092-8674(87)90663-5

Cited by 266 publications

(238 citation statements)

References 31 publications

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“…For example, in the lysis/lysogeny switch of bacteriophage λ, cro and repressor compete for related sites in the rightward operator 28 . In eukaryotes, a number of regulatory proteins have been shown to be members of protein families with related DNA-binding specificities [29][30][31][32][33][34][35][36][37] . In fact, a member of the nuclear hormone receptor family, thyroid hormone receptor, was recently shown to mediate negative effects on transcription from oestrogen-responsive DNA elements, apparently by competing with oestrogen receptor for binding to the elements 38 .…”

Section: Discussionmentioning

confidence: 99%

Activation and repression of transcription by homoeodomain-containing proteins that bind a common site

Jaynes

O’Farrell

1988

Nature

223

148

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The product of the fushi tarazu (ftz) gene is shown to be a site-dependent activator of transcription. In vitro-defined binding sites act as ftz-dependent enhancers in cultured cells. Another homoeodomain-containing protein, the engrailed gene product, competes for homoeodomainbinding sites and counteracts ftz activation.GENETIC analysis in Drosophila melanogaster has identified a group of regulatory genes that participate in embryonic pattern formation 1,2 . Many of these genes encode a 60 amino-acid sequence, the homoeodomain, that is highly conserved through evolution [3][4][5] . This domain contains a putative helix-turn-helix motif 6 such as that found in a number of bacterial regulators 7 , and possesses a sequence-specific DNA-binding activity 8,9 . Numerous regulatory interactions occur among homoeodomain-encoding genes during development. For example, a combination of segmentation and homoeotic gene products, many of which contain homoeodomains 1 , specify the developmental fates of cells in striped patterns 10,11 . Furthermore, homoeodomain-containing proteins (homoeodomain proteins) regulate both each other 12 and downstream (`cytodifferentiation' 13 ) genes. Consequently, it has been attractive to think of homoeodomain proteins as direct regulators of transcription. Due to the complexity of cross-regulatory interactions however, mutations altering or eliminating one homoeodomain protein generally change the expression patterns of many other regulators, confounding efforts to distinguish direct from indirect regulation. Additionally, suspected target genes contain large cis-acting control regions that respond, directly or indirectly, to complex combinations of regulators [14][15][16][17] . As a result, identification of target genes directly regulated by homoeodomain proteins has been problematic.Previous studies have documented instances in which homoeodomain proteins control transcription. The enhancer activity of a DNA fragment from the ftz gene, a homoeodomaincontaining member of the pair-rule class of segmentation genes, suggested that the ftz gene product (ftz) activates its own expression in the embryo 18 . In a different approach a Drosophila tissue culture system was used to show that the Ultrabithorax (Ubx) gene product induces expression of its own promoter, and inhibits the Antennapedia (Antp) (P1) promoter (M. Krasnow and D. S. Hogness, personal communication, see ref. 19 for summary). In these cases however, the complexity of the regulatory circuitry and of the responding control regions leaves open the possibility that the homoeodomain proteins produce these transcriptional effects through intermediaries. To circumvent the complexities of natural target genes, we chose to use binding sites identified in vitro to build homoeodomain-responsive promoters. We find that ftz is a potent activator of transcription from these promoters in cultured cells.During sequential subdivision of the Drosophila embryo to produce segmentally repeating patterns, combinations of regulatory gene prod...

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Section: Discussionmentioning

confidence: 99%

Activation and repression of transcription by homoeodomain-containing proteins that bind a common site

Jaynes

O’Farrell

1988

Nature

223

148

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“…Multiple initiation sites were mapped around nt 2440 and nt 3080 (Ahola et al, 1987;Baker & HoMey, 1987), the latter giving rise to transcripts potentially encoding the E2 transcriptional repressor protein (Lambert et aL, 1987). In BPV-4, a second ATG codon is found in the E20RF at nt 3149, and a third at nt 3158 (Fig.…”

Section: Protein-coding Potential Of the Minor Transcriptsmentioning

confidence: 99%

Mapping of Two Novel Transcripts of Bovine Papillomavirus Type 4

1988

Journal of General Virology

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SUMMARYA cDNA library was synthesized using RNA from bovine papillomavirus type 4 (BPV-4)-induced papillomas. The major viral transcript was characterized by sequencing of its cDNA, primer extension mapping and S 1 nuclease protection studies. The transcript initiates at multiple sites between nucleotide (nt) 777 and nt 902, contains a splice junction between nt 1016 and nt 3376 and terminates at nt 4034, using the early polyadenylation signal at nt 4009. Sequencing of viral cDNAs and mRNA revealed deviations from the reported genomic sequence between nt 3412 and nt 3460. These resulted in a temporary frameshift, abolished the translation termination codon of the E5a open reading flame (ORF), and introduced a new termination codon in the E40RF. The new uninterrupted E50RF was found to have greater homology to the E40RFs of other papillomaviruses than to their E50RFs. The E50RF of BPV-4 is joined to a five codon ORF in the leader exon of the major transcript, in the same way as the E40RF in the major transcripts of BPV-1 and human papillomavirus type 11. On this basis, it has been redesignated E4, and the viral genomic sequence revised. Two novel transcriptional promoters of BPV-4 were defined: a putative controller of the multiple major RNA start sites around nt 870 and a minor TATA box at nt 691. In addition, minor early region transcripts were mapped which initiate between nt 3071 and nt 3152. None of these transcripts utilizes the splice site at nt 3376. These messages may express E2-encoded functions.

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“…The protein is also required in association with the viral El protein for replication (22,23). In addition to the full-length E2 protein, BPV-1 expresses two functional N-terminally truncated polypeptides which may antagonise the activity of the full-length *To whom correspondence should be addressed transcriptional activator and have a role in autoregulation of viral transcription and replication (24)(25)(26)(27).…”

Section: Introductionmentioning

confidence: 99%

Kinetic and equilibrium binding studies of the human papillomavirus type-16 transcription regulatory protein E2 interacting with core enhancer elements

Sanders

Maitland

1994

Nucl Acids Res

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The human papillomaviruses (HPVs) are a family of DNA viruses which cause benign tumours of the skin and mucosa that infrequently progress to malignant carcinoma. The E2 open reading frame of HPV is thought to encode a papillomavirus-specific transcription factor which also has a role in viral replication. The E2 proteins of all papillomaviruses studied to date have been shown to bind specifically to the common conserved sequence ACC(N)6GGT found at multiple locations in their genomes. In the case of HPV-16, a 'high risk' genital papillomavirus, the E2 protein is thought to negatively regulate expression of the major viral transforming genes E6 and E7, which have been directly implicated in the oncogenic process. However, little information exists concerning the relative or absolute affinities of the native HPV-16 protein for its palindromic recognition sequences; moreover, interpretation of any transcription or replication phenomena attributed to this protein is more complicated in the absence of such data. Here we describe the overexpression, purification and characterisation of the C-terminal 89 amino acids of the protein encompassing the DNA binding/dimerisation domain. We show that the recombinant protein purified from E.coli by a combination of non-group-specific chromatography steps retains high biological activity and is able to bind to all sites in the HPV-16 genome with high affinity ( -8x 10-11 M). In addition, kinetic studies show that the E2 -DNA complexes are very stable, with half-lives ranging from 2.15 to greater than 240 min, and that nucleotides internal and external to the conserved palindrome appear to influence stability.

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A transcriptional repressor encoded by BPV-1 shares a common carboxy-terminal domain with the E2 transactivator

Cited by 266 publications

References 31 publications

Activation and repression of transcription by homoeodomain-containing proteins that bind a common site

Activation and repression of transcription by homoeodomain-containing proteins that bind a common site

Mapping of Two Novel Transcripts of Bovine Papillomavirus Type 4

Kinetic and equilibrium binding studies of the human papillomavirus type-16 transcription regulatory protein E2 interacting with core enhancer elements

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