Evidence for interaction of different eukaryotic transcriptional activators with distinct cellular targets

Martin, Katherine J.; Lillie, James W.; Green, Michael R.

doi:10.1038/346147a0

Cited by 225 publications

(205 citation statements)

References 41 publications

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“…Though such structures are known to be involved in protein-DNA interactions, TFIIB itself has no detectable DNA binding activity (26,31). Rather, as is supported by our data, it seems more likely that the finger region functions as a protein-protein interaction surface, much like the potential metal-binding domain found in the adenovirus E1a protein that appears to mediate contacts with TBP important for transcriptional activation (23,45). The zinc finger is conserved in TFIIB homologs from Saccharomyces cerevisiae to humans (9,52), and the TFIIB-like factor BRF1 (also known as TDS4 or PCF4), involved in transcription by RNAP III, also has the potential to form a zinc finger through N-terminal sequences (8,13,44).…”

Section: Discussionmentioning

confidence: 57%

A Direct Interaction between a Glutamine-Rich Activator and the N Terminus of TFIIB Can Mediate Transcriptional Activation In Vivo

Colgan

Ashali

Manley

1995

Molecular and Cellular Biology

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Studies examining the mechanism by which transcriptional activators function have suggested that the general transcription factor IIB (TFIIB) can be a target for certain regulatory proteins. For example, we showed previously that expression of a mutant form of TFIIB can specifically inhibit activation in vivo mediated by the strong, glutamine-rich activator protein GAL4-ftzQ. Using transient cotransfection assays, we have defined the regions in both GAL4-ftzQ and TFIIB that are required for activity in vivo and provide evidence that a potential zinc finger structure at the N terminus of TFIIB is necessary for the observed functional interaction between the two proteins. Using a protein binding assay, we have demonstrated that GAL4-ftzQ can specifically interact with TFIIB in vitro. This interaction requires the same regions in both molecules necessary for function in vivo and is reduced or eliminated by mutations predicted to disrupt the zinc finger in TFIIB. These results support the idea that a direct interaction between a regulatory protein and TFIIB can be important for transcriptional activation in vivo and, combined with previous data of others, suggest that different activators can function by contacting distinct regions of TFIIB.Initiation of transcription by RNA polymerase II (RNAP II) occurs through a complex set of interactions involving promoter DNA, a set of general transcription factors, and genespecific regulatory proteins. Promoters recognized by RNAP II usually consist of two classes of sequence elements in order to accomodate these interactions. Core, or basal, promoter elements include the TATA box and the initiator, which, individually or in tandem, can support the assembly of the general transcription factors into functional preinitiation complexes (for reviews, see references 5, 56, and 64). Core promoter elements are usually surrounded by members of the second class of promoter sequences, which consists of elements recognized by gene-specific factors that function to regulate the assembly and/or activity of the general transcription machinery (35,49,58).Principally through fractionation and reconstitution of transcription in vitro, the factors constituting the RNAP II general transcription machinery have been isolated and characterized (for reviews see references 6, 17, and 70). These general, or basal, transcription factors, designated TFIIA, -B, -D, -E, -F, and -H, were once thought to all be necessary in addition to the polymerase for transcription, but studies using a variety of promoters and/or more purified systems have suggested that several of these factors may be dispensible under certain conditions (19,25,39,51,59,60). The general factors can form preinitiation complexes on core promoter elements in vitro by way of an ordered assembly pathway involving protein-DNA and protein-protein contacts (7, 61). For TATA-containing promoters, this assembly process begins with the binding of TFIID to the TATA element, which may be facilitated by TFIIA, and is followed by the association of T...

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Section: Discussionmentioning

confidence: 57%

A Direct Interaction between a Glutamine-Rich Activator and the N Terminus of TFIIB Can Mediate Transcriptional Activation In Vivo

Colgan

Ashali

Manley

1995

Molecular and Cellular Biology

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“…E1A CR3 functions as a strong activation domain (AD) when tethered to a promoter by fusion to the Gal4 DNA-binding domain (Lillie and Green, 1989;Martin et al, 1990). This AD function is essential for activation of early viral promoters by the authentic E1A protein (Webster and Ricciardi, 1991).…”

Section: E1a Conserved Region 3 Activation Of Early Viral Gene Expresmentioning

confidence: 99%

Recent lessons in gene expression, cell cycle control, and cell biology from adenovirus

2005

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Adenovirus continues to be an important model system for investigating basic aspects of cell biology. Interactions of several cellular proteins with E1A conserved regions (CR) 1 and 2, and inhibition of apoptosis by E1B proteins are required for oncogenic transformation. CR2 binds RB family members, de-repressing E2F transcription factors, thus activating genes required for cell cycling. E1B-19K is a BCL2 homolog that binds and inactivates proapoptotic BAK and BAX. E1B-55K binds p53, inhibiting its transcriptional activation function. In productively infected cells, E1B-55K and E4orf6 assemble a ubiquitin ligase with cellular proteins Elongins B and C, Cullin 5 and RBX1 that polyubiquitinates p53 and one or more subunits of the MRN complex involved in DNA doublestrand break repair, directing them to proteosomal degradation. E1A CR3 activates viral transcription by interacting with the MED23 Mediator subunit, stimulating preinitiation complex assembly on early viral promoters and probably also the rate at which they initiate transcription. The viral E1B-55K/E4orf6 ubiquitin ligase is also required for efficient viral late protein synthesis in many cell types, but the mechanism is not understood. E1A CR1 binds several chromatin-modifying complexes, but how this contributes to stimulation of cellular DNA synthesis and transformation is not clear. E1A CR4 binds the CtBP corepressor, but the mechanism by which this modulates the frequency of transformation remains to be determined. Clearly, adenovirus has much left to teach us about fundamental cellular processes.

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“…The E70RF was fused with the Gal4 DNA-binding domain by transferring the HindlII-BamHI Gal4-containing fragment from Gal4VP16 (Martin et al, 1990) to pJ4f~16E7, then infilling the BamHI site to obtain fusion in the correct reading frame. The plasmids VP16-Rb and VP16-107 were constructed using fully sequenced PCR-derived products as follows.…”

Section: Trans-activation Of the Adenovirus E2 Promoter By Human Papimentioning

confidence: 99%

Trans-activation of the adenovirus E2 promoter by human papillomavirus type 16 E7 is mediated by retinoblastoma-dependent and -independent pathways

Carlotti

Crawford²

1993

Journal of General Virology

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In common with the adenovirus E1A and simian virus 40 large T oncoproteins, the E7 protein of human papiUomavirus (HPV) type 16 interacts with the retinoblastoma (Rb) tumour suppressor protein (pRb). The functional importance of this interaction for protein was investigated by analysis of the transactivating function of E7 at the adenovirus E2 promoter in a set of breast tumour cell lines. Trans-activation by HPV-16 E7 in two pRb-deficient cell lines demonstrated that pRb is not essential for E7-mediated transactivation, but reconstitution of Rb expression indicated the existence of an Rb-mediated pathway of E7 transactivation. This pathway results from suppression by E7 of a trans-repressing function encoded by the Rb gene. The E7 protein is shown to be capable of interacting in vivo with the Rb-related protein p107. Furthermore, analysis of a fusion construct between the amino terminus of Rb and the carboxy terminus of p107 suggests that, in common with pRb, the p107 protein trans-represses the adenovirus E2 early promoter.Therefore it is proposed that the pRb-independent pathway of E7 trans-activation is a consequence of the suppression of trans-repression by p107.

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Evidence for interaction of different eukaryotic transcriptional activators with distinct cellular targets

Cited by 225 publications

References 41 publications

A Direct Interaction between a Glutamine-Rich Activator and the N Terminus of TFIIB Can Mediate Transcriptional Activation In Vivo

A Direct Interaction between a Glutamine-Rich Activator and the N Terminus of TFIIB Can Mediate Transcriptional Activation In Vivo

Recent lessons in gene expression, cell cycle control, and cell biology from adenovirus

Trans-activation of the adenovirus E2 promoter by human papillomavirus type 16 E7 is mediated by retinoblastoma-dependent and -independent pathways

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