Several different upstream promoter elements can potentiate transactivation by the BPV-1 E2 protein.

Ham, Jonathan; Dostatni, Nathalie; Arnos, F; Yaniv, Moshe

doi:10.1002/j.1460-2075.1991.tb07843.x

Cited by 45 publications

(48 citation statements)

References 61 publications

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“…2 Previous studies have shown that a core promoter must contain at least two elements to be able to respond to E2 and that such elements, the TATA box, the initiator element, or a binding site for an upstream promoter factor, are interchangeable to a large extent (33). Therefore E2 requires the co-operation of at least one additional DNA binding proximal promoter factor, such as Sp1, or other factors that interact with papillomavirus promoters, such as AP-1, Oct-1, NF-1/CTF, or USF for the activation of a minimal TATA box promoter (28,34). Epithelial-specific functions of some of these factors have emerged.…”

Section: Discussionmentioning

confidence: 99%

An Enhanced Epithelial Response of a Papillomavirus Promoter to Transcriptional Activators

Vance¹,

Campo²,

Morgan³

1999

Journal of Biological Chemistry

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Section: Discussionmentioning

confidence: 99%

An Enhanced Epithelial Response of a Papillomavirus Promoter to Transcriptional Activators

Vance¹,

Campo²,

Morgan³

1999

Journal of Biological Chemistry

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“…Plasmid pC18-SP1-luc (a kind gift of G. Steger, Institute of Virology, Cologne, Germany) consists of four synthetic E2 binding sites (5Ј-CTAGACCGAAAACGGTG-3Ј) and two synthetic SP1 binding sites (5Ј-GATCTAAACCCCGCCCAGCCG-3Ј) upstream of a minimal adenovirus major late promoter composed of the TATA box and the initiator element inserted into the luciferase reporter plasmid pALuc (G. Steger, unpublished data). Plasmid pC18-luc, which is comparable to plasmid pC18 (19), was constructed by removing the SP1 binding sites from pC18-SP1-luc by BamHI digestion. E2 and SP1 binding sites were deleted from plasmid pC18-luc by digesting with HindIII and BamHI, filling in the ends with Klenow polymerase, and religating the fragments.…”

Section: Methodsmentioning

confidence: 99%

The E8 Domain Confers a Novel Long-Distance Transcriptional Repression Activity on the E8^E2C Protein of High-Risk Human Papillomavirus Type 31

Stubenrauch

Zobel

Iftner

2001

J Virol

102

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Infections with high-risk human papillomaviruses (HPVs) are the major risk factor for the development of anogenital cancers. Viral E2 proteins are involved in viral DNA replication and regulation of transcription. Repression of the viral P97 promoter by E2 proteins has been implicated in the modulation of the immortalization capacity and DNA replication properties of high-risk HPVs. Analysis of the cis and trans requirements for repression of the HPV type 31 (HPV31) P97 promoter, however, revealed striking differences between the full-length E2 and the E8ˆE2C fusion protein which were due to conserved residues W6 and K7 of the E8 domain. In contrast to E2, E8ˆE2C completely inhibited the P97 promoter from a single promoter-distal E2 binding site. This novel long-distance repression activity of the E8 domain also enabled E8ˆE2C to inhibit the HPV6a P2 promoter and minimal-promoter constructs containing E2 binding sites. Thus, E8ˆE2C may represent the master repressor of viral gene expression during a high-risk HPV infection, and changes in the activity of E8ˆE2C might contribute to the progression of high-risk HPV-induced lesions.The replication cycle of human papillomaviruses (HPVs) can be divided into two stages. In the basal cell layer of the epidermis, which is composed of division-competent keratinocytes, HPVs establish a persistent, nonproductive infection in which viral DNA genomes are replicated as extrachromosomal elements at low levels and only early viral genes are transcribed. The productive viral replication cycle occurs upon differentiation of infected keratinocytes, which results in highlevel replication of viral genomes, induction of late-gene transcription, and synthesis of infectious virions (22,49).Infections with a subset of HPV types dramatically increase the risk for the development of malignancies of the anogenital tract, and these types have been designated as high-risk HPVs (56,57). Within this group, high-risk HPV type 16 (HPV16), HPV18, and HPV31 have been most intensively studied at the molecular level. Expression of the early E6 and E7 gene products of high-risk HPVs is sufficient to immortalize normal human keratinocytes (NHKs), the natural target cells for HPVs (34). This property is not shared by E6 and E7 genes from low-risk HPV6 and HPV11 and is therefore regarded as being relevant to the carcinogenic potential of high-risk HPVs (34). The exact molecular events that lead to malignant progression of high-risk HPV-induced lesions are still largely unknown.Several lines of evidence suggest that transcriptional modulation of early viral gene expression is a central regulatory event. In the absence of viral gene products, HPV early-gene transcription is activated by a variety of host cell transcription factors, which interact with regulatory sequences located upstream of the major early promoter of high-risk HPV16, -18, and -31, designated P97 for HPV16 and -31 and P105 for HPV18 (22). The basal activity of HPV early promoters can be further modulated by viral E2 proteins, which are s...

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“…Repression of HPV gene expression by the E2 activator protein occurs when E2 binding sites are overlapping with the binding sites for cellular transcription factors necessary for promoter activity. In contrast to natural HPV promoter-enhancer constellations E2 can strongly activate synthetic promoters containing several E2 binding sites upstream of a promoter, although specific differences in the mode of activation between the E2 proteins of different types may exist (18,27,61). In addition to its role in regulation of gene expression, E2 is also necessary for viral DNA replication.…”

mentioning

confidence: 99%

Cooperative Activation of Human Papillomavirus Type 8 Gene Expression by the E2 Protein and the Cellular Coactivator p300

Müller

Ritzkowsky

Steger

2002

J Virol

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The E2 proteins of papillomaviruses (PV) bind to the coactivator CBP/p300 as do many other transcription factors, but the precise role of CBP/p300 in E2-specific functions is not yet understood. We show that the E2 protein of human PV type 8 (HPV8) directly binds to p300. Activation of HPV8 gene expression by low amounts of HPV8 E2 was stimulated up to sevenfold by coexpression of p300. The interaction between E2 and p300 may play a role in differentiation-dependent activation of PV gene expression, since we can show that the expression level of p300 increases during keratinocyte differentiation. Surprisingly, sequence-specific binding of E2 to its recognition sites within the regulatory region of HPV8 is not necessary for this cooperation, indicating that E2 can be recruited to the promoter via protein-protein interaction. HPV8 E2 binds via its N-terminal activation domain (AD), its C-terminal DNA binding domain (DBD), and its internal hinge region to p300 in vitro. Transient-transfection assays revealed that the AD is necessary and sufficient for cooperative activation with p300. However, we provide evidence that the interaction of the hinge and the DBD of HPV8 E2 with p300 may contribute. Our data suggest an important role of p300 in regulation of HPV8 gene expression and reveal a new mechanism by which E2 may be recruited to a promoter to activate transcription without sequence specific DNA binding.Papillomaviruses (PV) infect the basal cells of the skin or the mucosa, causing proliferative lesions like warts or dysplasias. PV require differentiating keratinocytes to replicate their DNA. The expression of the structural proteins is restricted to some of the most-differentiated keratinocytes. This cell tropism is due to the involvement of transcription factors specifically expressed in these cells. In addition to ubiquitously expressed and keratinocyte-specific cellular transcription factors, viral gene expression is also modulated by the viral E2 protein. The E2 protein binds via its carboxy (C)-terminal DNA binding domain (DBD) and dimerization domain to the 12-bp palindromic sequence ACCN 6 GGT mostly located within the regulatory region, also called the long control region or noncoding region (NCR) of the PV genome. In the case of bovine PV type 1 (BPV1), the long control region contains 12 E2 binding sites, which mediate a strong activation of several BPV1 promoters by E2 (48-50). Human PV (HPV) types infecting the genital mucosa contain four E2 binding sites in conserved positions. Here, only a moderate activation by E2 could be detected, and E2 repressed HPV gene expression in most cases. This repression is mediated by binding to two promoter-proximal E2 binding sites, as revealed by transient transfections of cervical carcinoma cell lines and immortalized skin keratinocytes (10,52,58,59). Repression of HPV gene expression by the E2 activator protein occurs when E2 binding sites are overlapping with the binding sites for cellular transcription factors necessary for promoter activity. In contrast to nat...

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Several different upstream promoter elements can potentiate transactivation by the BPV-1 E2 protein.

Cited by 45 publications

References 61 publications

An Enhanced Epithelial Response of a Papillomavirus Promoter to Transcriptional Activators

An Enhanced Epithelial Response of a Papillomavirus Promoter to Transcriptional Activators

The E8 Domain Confers a Novel Long-Distance Transcriptional Repression Activity on the E8^E2C Protein of High-Risk Human Papillomavirus Type 31

Cooperative Activation of Human Papillomavirus Type 8 Gene Expression by the E2 Protein and the Cellular Coactivator p300

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