scholarly journals Adenovirus type 5 E1A gene products act as transformation suppressors of the neu oncogene.

1991 ◽  
Vol 11 (3) ◽  
pp. 1745-1750 ◽  
Author(s):  
D H Yu ◽  
K Scorsone ◽  
M C Hung
Keyword(s):  
Nude Mice ◽  
Adenovirus Type ◽  
Transformed Cells ◽  
Gene Products ◽  
Early Region ◽  
Transforming Activity ◽  
Neu Oncogene ◽  
E1a Gene ◽  
Adenovirus Type 5

The adenovirus type 5 early region 1A (E1A) gene was introduced into neu-transformed B104-1-1 cells. Cells that expressed E1A possessed reduced transforming activity in vitro and reduced tumorigenicity in nude mice. These results demonstrate that the E1A gene products can act negatively to suppress the transformed phenotype in neu-transformed cells.

Adenovirus type 5 E1A gene products act as transformation suppressors of the neu oncogene

1991 ◽  
Vol 11 (3) ◽  
pp. 1745-1750
Author(s):  
D H Yu ◽  
K Scorsone ◽  
M C Hung
Keyword(s):  
Nude Mice ◽  
Adenovirus Type ◽  
Transformed Cells ◽  
Gene Products ◽  
Early Region ◽  
Transforming Activity ◽  
Neu Oncogene ◽  
E1a Gene ◽  
Adenovirus Type 5

The adenovirus type 5 early region 1A (E1A) gene was introduced into neu-transformed B104-1-1 cells. Cells that expressed E1A possessed reduced transforming activity in vitro and reduced tumorigenicity in nude mice. These results demonstrate that the E1A gene products can act negatively to suppress the transformed phenotype in neu-transformed cells.

scholarly journals A novel general approach to eucaryotic mutagenesis functionally identifies conserved regions within the adenovirus 13S E1A polypeptide.

1986 ◽  
Vol 6 (5) ◽  
pp. 1487-1496 ◽  
Author(s):  
D Kimelman
Keyword(s):  
Shuttle Vector ◽  
Point Mutations ◽  
Mutant Gene ◽  
Adenovirus Type ◽  
Cellular Morphology ◽  
Morphological Alteration ◽  
Morphological Alterations ◽  
E1a Gene ◽  
Adenovirus Type 5

A new approach to the isolation of mutations in mammalian genes was developed which permits both the selection of infrequently occurring mutants that alter the cellular morphology of recipient cells and the rapid reisolation of the mutant gene. The adenovirus type 5 13S early region 1a (E1a) gene was mutagenized in vitro with sodium bisulfite and then efficiently transferred into cells with a retrovirus shuttle vector. Three classes of mutants of the 13S E1a gene product were isolated, each of which induced a distinct morphological alteration. The mutant E1a gene was reisolated from each cell line, and the precise nucleotide changes were determined. The E1a-induced morphological alterations were further examined by the construction of single and double point mutations within different regions of the polypeptides by utilizing the amino acid substitutions obtained from the original mutants. The results suggest that each of the three regions of highly conserved amino acids within the E1a 13S polypeptide has a distinct role in the alteration of cellular morphology and the activation of gene expression.

scholarly journals Tumorigenicity of fibroblast lines expressing the adenovirus E1a, cellular p53, or normal c-myc genes.

1986 ◽  
Vol 6 (1) ◽  
pp. 7-14 ◽  
Author(s):  
A Kelekar ◽  
M D Cole
Keyword(s):  
Simian Virus 40 ◽  
Adenovirus Type ◽  
Simian Virus ◽  
Primary Cells ◽  
Adenovirus E1a ◽  
Immortalized Cells ◽  
Transforming Activity ◽  
E1a Gene

Cellular and viral oncogenes have been linked to the transformation of established cell lines in vitro, to the induction of tumors in vivo, and to the partial transformation or immortalization of primary cells. Based on the ability to cooperate with mutated ras oncogenes in the transformation of primary cells, the adenovirus E1a and cellular p53 genes have been assigned an immortalizing activity. It is demonstrated in this paper that the adenovirus type 5 E1a gene and simian virus 40 promoter-linked p53 cDNA are able to transform previously immortalized cells to a tumorigenic phenotype without a significant change in cell morphology. It is also shown that, when linked to a constitutive promoter, the normal mouse and human c-myc genes have the same transforming activity. Cells transformed by each of these oncogenes have an increased capacity to grow in the absence of growth factors and a limited anchorage-independent growth capability.

scholarly journals Individual adenovirus type 5 early region 1A gene products elicit distinct alterations of cellular morphology and gene expression.

1985 ◽  
Vol 56 (2) ◽  
pp. 404-413 ◽  
Author(s):  
B E Roberts ◽  
J S Miller ◽  
D Kimelman ◽  
C L Cepko ◽  
I R Lemischka ◽  
...  
Keyword(s):  
Gene Expression ◽  
Adenovirus Type ◽  
Cellular Morphology ◽  
Gene Products ◽  
Early Region ◽  
Adenovirus Type 5

A novel general approach to eucaryotic mutagenesis functionally identifies conserved regions within the adenovirus 13S E1A polypeptide

1986 ◽  
Vol 6 (5) ◽  
pp. 1487-1496
Author(s):  
D Kimelman
Keyword(s):  
Shuttle Vector ◽  
Point Mutations ◽  
Mutant Gene ◽  
Adenovirus Type ◽  
Cellular Morphology ◽  
Morphological Alteration ◽  
Morphological Alterations ◽  
E1a Gene ◽  
Adenovirus Type 5

A new approach to the isolation of mutations in mammalian genes was developed which permits both the selection of infrequently occurring mutants that alter the cellular morphology of recipient cells and the rapid reisolation of the mutant gene. The adenovirus type 5 13S early region 1a (E1a) gene was mutagenized in vitro with sodium bisulfite and then efficiently transferred into cells with a retrovirus shuttle vector. Three classes of mutants of the 13S E1a gene product were isolated, each of which induced a distinct morphological alteration. The mutant E1a gene was reisolated from each cell line, and the precise nucleotide changes were determined. The E1a-induced morphological alterations were further examined by the construction of single and double point mutations within different regions of the polypeptides by utilizing the amino acid substitutions obtained from the original mutants. The results suggest that each of the three regions of highly conserved amino acids within the E1a 13S polypeptide has a distinct role in the alteration of cellular morphology and the activation of gene expression.

scholarly journals The abundance and in vitro DNA binding of three cellular proteins interacting with the adenovirus EIIa early promoter are not modified by the EIa gene products.

1987 ◽  
Vol 7 (10) ◽  
pp. 3806-3817 ◽  
Author(s):  
P Jalinot ◽  
B Devaux ◽  
C Kédinger
Keyword(s):  
Binding Sites ◽  
Adenovirus Type ◽  
Specific Protein ◽  
Gene Products ◽  
Wild Type ◽  
Band Shift ◽  
Transcription Complexes ◽  
Adenovirus Type 5 ◽  
Band Shift Assay

Specific protein binding on the EIa-inducible adenovirus EIIa early (EIIaE) promoter was analyzed by the sensitive electrophoretic band-shift assay and by protection against DNase I digestion. Three factors were identified, and precise mapping of the cognate-binding sites revealed their correspondence to promoter elements essential for constitutive EIIaE transcription. One binds to the major upstream element located between -82 and -64 (with respect to the major EIIaE cap site), another appears to interact with sequences on either side of this region, and the last one binds to an element located further upstream. Comparison of the binding activities of the factors present in extracts from cells infected with wild-type adenovirus (adenovirus type 5) or with the EIa deletion mutant dl312 did not reveal striking differences. Not only were the general binding patterns indistinguishable, but the concentration of each of the identified factors as well as their affinity for the cognate-binding sites were unchanged. Our results suggest that the EIa-mediated activation of the EIIaE transcription complexes involves appropriate interactions between transcription factors, rather than their increased binding to DNA.

Tumorigenicity of fibroblast lines expressing the adenovirus E1a, cellular p53, or normal c-myc genes

1986 ◽  
Vol 6 (1) ◽  
pp. 7-14
Author(s):  
A Kelekar ◽  
M D Cole
Keyword(s):  
Simian Virus 40 ◽  
Adenovirus Type ◽  
Simian Virus ◽  
Primary Cells ◽  
Adenovirus E1a ◽  
Immortalized Cells ◽  
Transforming Activity ◽  
E1a Gene

Cellular and viral oncogenes have been linked to the transformation of established cell lines in vitro, to the induction of tumors in vivo, and to the partial transformation or immortalization of primary cells. Based on the ability to cooperate with mutated ras oncogenes in the transformation of primary cells, the adenovirus E1a and cellular p53 genes have been assigned an immortalizing activity. It is demonstrated in this paper that the adenovirus type 5 E1a gene and simian virus 40 promoter-linked p53 cDNA are able to transform previously immortalized cells to a tumorigenic phenotype without a significant change in cell morphology. It is also shown that, when linked to a constitutive promoter, the normal mouse and human c-myc genes have the same transforming activity. Cells transformed by each of these oncogenes have an increased capacity to grow in the absence of growth factors and a limited anchorage-independent growth capability.

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