Nuclear factor III, a novel sequence-specific DNA-binding protein from HeLa cells stimulating adenovirus DNA replication

Pruijn, Ger J. M.; Driel, W. Van; Vliet, Peter C. van der

doi:10.1038/322656a0

Cited by 250 publications

(146 citation statements)

References 31 publications

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“…The nuclei were suspended in the same buffer also containing 1 mM EDTA. Nuclear proteins were extracted by the addition of 5 M KCl to a final concentration of 0.3 M. After centrifugation the final supernatant was adjusted to 0.1 M KCl by the addition of buffer A100 [20,21].…”

Section: Preparation Of Cell Extractsmentioning

confidence: 99%

Identification of a key regulatory element for the basal activity of the human insulin-like growth factor II gene promoter P3

Rietveld

Holthuizen

Sussenbach

1997

Biochemical Journal

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Transcription of the human insulin-like growth factor II (IGF-II) gene is under the control of four promoters (P1-P4) that are differentially active during growth and development. Promoter 3 (P3) is the most active promoter during fetal development as well as in most adult tissues. P3 is also the most active promoter in tumour tissues and cell lines expressing IGF-II. Transient transfections of HeLa and Hep3B cells with truncated promoter constructs revealed that the region between -289 and -183 relative to the transcription start site supports basal promoter activity in both cell lines. Footprint experiments showed that the region between positions -192 and -172 (P3-4) is the only element bound by nuclear proteins. P3-4 is bound by five proteins, of which three proteins (proteins 3, 4 and 5) bind specifically and are expressed at the same levels in HeLa and Hep3B cells. Electrophoretic mobility shift assays and differential footprint experiments revealed the presence of two protein-binding regions within the P3-4 element. Proteins 4 and 5 bind box A (-193 to -188), whereas box B (-183 to -172) is bound by protein 3. From transcription experiments in vitro it can be concluded that Box A is essential for P3 activity. Box A is part of a region 11 dG residues long and is protected by proteins 4 and 5 that bind a contiguous set of six dG residues. DNA-binding of proteins 4 and 5 to box A requires the presence of Zn2+ ions. Thus structural and functional analysis reveals that the P3-4 element is a key regulatory element of P3 that contains two separate binding sites for proteins essential for the basal activity of IGF-II P3.

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Section: Preparation Of Cell Extractsmentioning

confidence: 99%

Identification of a key regulatory element for the basal activity of the human insulin-like growth factor II gene promoter P3

Rietveld

Holthuizen

Sussenbach

1997

Biochemical Journal

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“…The purification procedures for DBP [33], the complex of pTP and the Ad DNA polymerase (pTP-pol [34]), NFI [35], NFIII [13] and HeLa cytosol [36] were as described. The C-terminal 39 kDa DBP fragment was prepared by digestion with chymotrypsin in 2 M NaC1 [37] followed by DNA-cellulose chromatography.…”

Section: In Vitro Dna Replication Assaymentioning

confidence: 99%

“…The 3'-OH group of dCMP functions as primer for further DNA chain elongation [9][10][11]. Two cellular proteins, nuclear factors I and III (NFI and NFIII) greatly enhance the rate of initiation by binding specifically to the origin [12][13][14]. Recognition sequences for NFI and NFIII in the Ad2 origin are closely spaced and their relative position is rather critical [8,15,16].…”

Section: Introductionmentioning

confidence: 99%

Adenovirus DNA replication in vitro: Duplication of single-stranded DNA containing a panhandle structure

Leegwater

Rombouts

Vliet

1988

Biochimica et Biophysica Acta (BBA) - Gene Structure and Expres

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Adenovirus DNA replicates by displacement of one of the parental strands followed by duplication of the displaced parental single strand (complementary strand synthesis). Displacement synthesis has been performed in a reconstituted system composed of viral and cellular proteins, employing either the viral DNA-terminal protein complex as template or linearized plasmids containing the origin. Previously, evidence was obtained that in vivo complementary strand synthesis requires formation of a panhandle structure originating from hybridization of the inverted terminal repeats. To study the conditions for complementary strand synthesis in vitro, we have constructed an artificial panhandle molecule that contains a double-stranded inverted terminal repetition (ITR) region and a single-stranded loop derived from the left and right terminal Xma I fragments of Ad2. Such a molecule appeared to be an efficient template and could initiate by the same protein-priming mechanism as double-stranded DNA, employing the precursor terminal protein. The efficiency of both types of template was comparable. Like for replication of the duplex molecule initiation of panhandle replication was stimulated by nuclear factors I and III, proteins that bind to specific double-stranded regions of the ITR. The Ad DNA-binding protein is essential and the 39 kDa C-terminal domain of this protein that harbors the DNA-binding properties is sufficient for its function. These results support the hypothesis that panhandle formation is required for duplication of the displaced strand.

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“…However, some cellular nuclear proteins (factors I and II) have been identified that are complementary to the initiation and elongation of Ad-DNA replication. 29,30 Viral particle assembly Assembly of the Ad virion generally has been described as consisting of the following steps: (a) formation of the major structural unit of capsid, (i.e., capsomers of hexon and penton), (b) assembly of empty capsids, (c) insertion of viral DNA into capsids, and (d) proteolytic cleavage of maturation. 3 During this process, the encapsidation mechanism of viral genome into viral particles is the most critical step and is of interest for the development of Ad vectors.…”

Section: Viral Dna Replicationmentioning

confidence: 99%

Development and application of adenoviral vectors for gene therapy of cancer

Zhang¹

1999

Cancer Gene Ther

165

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For successful gene vaccination and therapy of cancer, it is essential to develop gene delivery vectors that can meet clinical and social requirements. The need for improved vectors was clearly manifested during the peak of the first wave of gene therapy. Adenoviral (Ad) vectors have recently drawn the attention of many of those involved in the field of gene therapy for cancer because of their practical advantages and application potential. Many experiments, innovations, preclinical studies, and clinical trials have generated an overwhelming amount of data and literature concerning this vector system. It is hoped that the comprehensive review presented here, which includes the principles, potential, capacity, and limitations of the current Ad systems, will help to further the rational development of the system. The literature in this article is organized in an attempt to emphasize Ad vector development in the aspects of technical approaches, practical hurdles and strategies to overcome them, significant experimental results, recent advances, future directions, etc. The technical range of this review covers details that are intended to serve as a reference for advanced technical readers and provide a foundation for initiates in the field of Ad vector gene therapy. The material presented here is also intended for nontechnical persons who want to have an overview of the significance and potential of the technology.

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Nuclear factor III, a novel sequence-specific DNA-binding protein from HeLa cells stimulating adenovirus DNA replication

Cited by 250 publications

References 31 publications

Identification of a key regulatory element for the basal activity of the human insulin-like growth factor II gene promoter P3

Identification of a key regulatory element for the basal activity of the human insulin-like growth factor II gene promoter P3

Adenovirus DNA replication in vitro: Duplication of single-stranded DNA containing a panhandle structure

Development and application of adenoviral vectors for gene therapy of cancer

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