Partial transformation of primary rat cells by the leftmost 4.5% fragment of adenovirus 5 DNA

Houweling, Ada; Elsen, Peter J. van den; Eb, A. J. Van Der

doi:10.1016/0042-6822(80)90054-9

Cited by 447 publications

(234 citation statements)

References 19 publications

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“…expression of the E1A and E1B oncogenes (Graham, 1984). While E1A-immortalized BRK cells often resemble the primary parental cells (Houweling et al, 1980;Shiroki et al, 1981;Bernards et al, 1986) the apparent morphological changes associated with complete transformation by E1A and E1B are induced by a combinatorial e ect of both E1B proteins (White and Cipriani, 1990). To test whether E4orf6 expression confers additional morphological changes to transformed rat cells expressing E1A and E1B, we compared the morphology of AB and ABS cells (Figure 3).…”

Section: Generation and Protein Analysis Of Transformed Brk Cellsmentioning

confidence: 99%

The adenovirus E4orf6 protein contributes to malignant transformation by antagonizing E1A-induced accumulation of the tumor suppressor protein p53

et al. 1999

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The adenovirus type 5 (Ad5) E4orf6 protein promotes focus formation of primary baby rat kidney (BRK) cells in cooperation with Ad5 E1 proteins. This activity is most likely related to the ability of the E4orf6 protein to bind to p53 and modulate its tumor suppressor functions. In this study we report that transformed BRK cells that stably express E4orf6 in addition to E1A and E1B (ABS cells) displayed multiple additional properties commonly associated with a high grade of oncogenic transformation compared to cells expressing only E1A and E1B (AB cells). These properties included morphological alterations, markedly enhanced growth rates and growth to much higher saturation densities. Following injection into nude mice ABS-derived tumors exhibited accelerated growth and, based on histopathological criteria, proofed to be much more malignant compared to tumors generated by AB cells. Interestingly, these highly transformed properties of ABS cells correlated with a dramatic reduction of p53 steady-state levels which inversely correlated with E4orf6 expression. From these results we conclude that expression of the Ad5 E4orf6 protein (i) confers additional transformed in vitro properties to primary rat cells expressing the Ad5 E1 proteins, and (ii) increases the tumorigenic and malignant potential of these cells in vivo. Our data suggest that the Ad5 E4orf6 protein enhances the intrinsic ability of E1-transformed rat cells to grow in a neoplastic state by completely inactivating p53 tumor suppressor function in combination with the E1A and E1B proteins.

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Section: Generation and Protein Analysis Of Transformed Brk Cellsmentioning

confidence: 99%

The adenovirus E4orf6 protein contributes to malignant transformation by antagonizing E1A-induced accumulation of the tumor suppressor protein p53

et al. 1999

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“…ElA alone can generate immortalized cell lines from primary cultures (14). It might be anticipated that the transcriptional regulatory activity of ElA with respect to cellular genes might be part of this process.…”

Section: Simon Et Al In Preparation)mentioning

confidence: 99%

“…Introduction of the ElA gene into primary cell cultures can lead to immortalization (14). In combination with E1B or other oncogenes, ElA expression can transform cells to an oncogenic state (9,23,43,49).…”

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confidence: 99%

Selective induction of human heat shock gene transcription by the adenovirus E1A gene products, including the 12S E1A product.

Simon¹,

Kitchener²,

Kao³

et al. 1987

Mol. Cell. Biol.

111

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We have previously shown that the human 70-kilodalton heat shock protein gene (hsp7O) is induced by the adenovirus ElA gene product and during the S-G2 phase of the cell cycle. In this study, we investigated the effect of ElA on the expression of other human hsp genes. A gene encoding one form of the hsp89 protein (hsp89a) was activated during an adenovirus infection with kinetics similar to those of activation of hsp7O. The induction required a functional ElA gene. However, the hsp89 transcript was not cell cycle regulated. Genes encoding another form of hsp89 and the hsp27 protein were not induced by ElA or during the cell cycle. Further examination of hsp7O expression revealed a greater complexity than previously seen. Si nuclease analysis using an hsp70 cDNA as well as a distinct hsp7O genomic clone demonstrated three related hsp70 transcripts; two were induced by ElA, and one was not. Both of the ElA-inducible genes were regulated during the cell cycle. All three were induced by heat shock. These results suggest common aspects of control among certain members of this family of cellular genes distinct from heat shock control. Finally, using viruses that express the individual ElA proteins, we found that the hsp70 gene is induced by the 12S and the 13S ElA products. The efficiency of induction by the 12S product was somewhat less than that by the 13S product but only by a factor of less than 2. This is in contrast to the induction of early viral genes, for which the 13S product is considerably more efficient than the 12S product.

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“…The E1 region contains two transcription blocks ± E1A and E1B (Boulanger and Blair, 1991). The E1A proteins are essential for transformation (Boulanger and Blair, 1991;Bayley and Mymryk, 1994) and may, on occasion, transform cells in the absence of co-operating oncogenes (Houweling et al, 1980;Gallimore et al, 1985b). It is generally considered that this activity of E1A is attributable to its interaction with important cellular components, many of which are involved in transcriptional regulation, such as pRb and the related p107 and p130, p300/CBP and the C-terminal binding protien (Boulanger and Blair, 1991;Bayley and Mymryk, 1994;Moran, 1994).…”

Section: Introductionmentioning

confidence: 99%

Definition of a major p53 binding site on Ad2E1B58K protein and a possible nuclear localization signal on the Ad12E1B54K protein

et al. 1999

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Previous studies have established that adenovirus 2/5 early region 1B (Ad E1B) 58K protein binds p53 strongly and co-localizes with it to cytoplasmic dense bodies whilst the homologous Ad12E1B54K protein binds only weakly and co-localizes primarily to the nucleus in Ad12E1 transformed cells. We have used these properties of the E1B proteins from di erent viral serotypes to map the p53 binding site on the Ad2/5 protein. A set of chimaeric genes was constructed containing di erent proportions of the Ad12 and Ad2E1B DNA. These, together with Ad12E1A and E1B19K DNA, were transfected into baby rat kidney cells and transformed lines isolated. From an examination of the properties of these Ad12/Ad2E1B fusion proteins in co-immunoprecipitation and subcellular localization experiments it has been concluded that the p53 binding site on Ad2E1B58K protein lies between amino acids 216 and 235 and that the homologous region on Ad12E1B54K protein also binds p53. In addition, a unique nuclear localization signal is located on Ad12E1B54K between residues 228 and 239. We suggest that primary structure di erences in these regions of the Ad2 and Ad12E1B proteins are responsible for the di erent subcellular localizations in AdE1 transformants.

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Partial transformation of primary rat cells by the leftmost 4.5% fragment of adenovirus 5 DNA

Cited by 447 publications

References 19 publications

The adenovirus E4orf6 protein contributes to malignant transformation by antagonizing E1A-induced accumulation of the tumor suppressor protein p53

The adenovirus E4orf6 protein contributes to malignant transformation by antagonizing E1A-induced accumulation of the tumor suppressor protein p53

Selective induction of human heat shock gene transcription by the adenovirus E1A gene products, including the 12S E1A product.

Definition of a major p53 binding site on Ad2E1B58K protein and a possible nuclear localization signal on the Ad12E1B54K protein

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