Cell Transformation: A Study of Regulation with Types 5 and 12 Adenovirus Temperature-sensitive Mutants

Ginsberg, Harold S.; Ensinger, M J; Kauffman, Robert S.; Mayer, Allen; Lundholm, Ulla

doi:10.1101/sqb.1974.039.01.054

Cited by 118 publications

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“…Hence, the isolation and characterization of temperature-sensitive mutants of adenoviruses (7)(8)(9)(10) suggested that they, too, may be useful to identify the critical gene(s) involved in, and to detect the gene product(s) essential for, transformation. In contrast to our expectation from data obtained with Rous sarcoma (1) and SV40 (2) viruses, however, an adenovirus mutant defective in DNA replication (5), H5ts125, was discovered that transformed rat embryo cells at frequencies 3 to 8 times greater than wild-type 5 adenovirus at the nonpermissive (39.50) and semipermissive (36°) temperatures (11,12). This finding implies that a specific viral gene product affects transformation, perhaps by modulating against it, so that, when the viral protein is nonfunctional or functions aberrantly, transformation is less restricted.…”

contrasting

confidence: 54%

Persistence of type 5 adenovirus DNA in cells transformed by temperature-sensitive mutant, H5ts125.

Mayer¹,

Ginsberg²

1977

Proc. Natl. Acad. Sci. U.S.A.

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The characteristic of H5ts125, a temperaturesensitive DNA-minus mutant, to transform 3 to 8 times more rat embryo cells than wild-type 5 adenovirus was correlated with the persistence of an increased proportion of the viral genome in cells independently transformed at the nonpermissive (39.50) or semipermissive (360) temperature. Reassociation (3)(4)(5)(6). Hence, the isolation and characterization of temperature-sensitive mutants of adenoviruses (7-10) suggested that they, too, may be useful to identify the critical gene(s) involved in, and to detect the gene product(s) essential for, transformation. In contrast to our expectation from data obtained with Rous sarcoma (1) and SV40 (2) viruses, however, an adenovirus mutant defective in DNA replication (5), H5ts125, was discovered that transformed rat embryo cells at frequencies 3 to 8 times greater than wild-type 5 adenovirus at the nonpermissive (39.50) and semipermissive (36°) temperatures (11,12). This finding implies that a specific viral gene product affects transformation, perhaps by modulating against it, so that, when the viral protein is nonfunctional or functions aberrantly, transformation is less restricted. A single-strand specific DNA-binding protein has been identified as the viral protein encoded in the ts125-mutated gene (13)

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contrasting

confidence: 54%

Persistence of type 5 adenovirus DNA in cells transformed by temperature-sensitive mutant, H5ts125.

Mayer¹,

Ginsberg²

1977

Proc. Natl. Acad. Sci. U.S.A.

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“…However, ts mutants in viral DNA synthesis exist both for adenoviruses (13) and papovaviruses (14). Temperature-sensitive mutants in Ad DNA synthesis have been studied for Ad5 (15,16), Adl2 (17), and Ad31 (18). Thus far, three complementation groups have been defined among the various ts Ad DNA negative mutants.…”

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confidence: 99%

Temperature-sensitive replication of H5ts125 adenovirus DNA in vitro.

Horwitz¹

1978

Proc. Natl. Acad. Sci. U.S.A.

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A soluble adenovirus DNA replication system has been prepared in extracts of HeLa cells infected with the temrperature-sensitive mutant HMts125. These nuclear extracts synthesize full-sized viral DNA at 300 but are temperature sensitive in this function at 380. A 72,000-dalton DNA-binding protein purified from cells infected with wild-type virus complements the temperature-sensitive defect and restores viral DNA replication to 74% of normal values. We have recently described the preparation of a nuclear extract from adenovirus (Ad)infected cells that catalyzed the synthesis of viral DNA in a manner analogous to that used in whole cells (1). These extracts, which were free of chromosomal DNA, contained replicating Ad DNA and synthesized full-size viral DNA products. Similar approaches developed in prokaryotes and their infecting bacteriophages have allowed the analysis of various gene products required for DNA initiation and elongation (2)(3)(4)(5). The general approach has been to prepare extracts from bacterial cell mutants that are temperature sensitive (ts) in DNA synthesis and to use these extracts as a receptor to isolate biochemically complementing activity from wild-type

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“…It also appears to be involved at some step in the establishment of cell transformation, since temperature-sensitive mutants of the DNA-binding protein transform rat cells in culture with a higher efficiency than wild-type virus [18]. Cells transformed by these mutants contain extensive regions of the viral genome integrated into their chromosomes, whereas wild-type transformants do not [19].…”

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confidence: 99%

Protein Kinases Associated with the Adenovirus Single‐Stranded DNA‐Binding Protein

Cajean-Feroldi

Loeb

Meguenni

et al. 1981

European Journal of Biochemistry

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Protein kinase activities copurifying with the 7200‐MrDNA‐binding protein of adenovirus on DNA‐cellulose chromatography and gel filtration in acrylamide/agarose have been partially characterized and purified. One of these kinases was found to phosphorylate efficiently the viral DNA‐binding protein in vitro and to be stimulated severalfold by the addition of histones, protamine, or polyamines. The kinase does not, however, phosphorylate histones, protamine, casein, or phosvitin. A second protein kinase was also recovered from single‐stranded DNA‐cellulose which is able to phosphorylate the 72000‐Mr DNA‐binding protein, but which is inhibited by the addition of histones. Phosphorylation in vitro of the 72000‐Mr DNA‐binding protein from the ts125 mutants of adenovirus by the histone‐stimulated protein kinase was found to be thermosensitive.

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Cell Transformation: A Study of Regulation with Types 5 and 12 Adenovirus Temperature-sensitive Mutants

Cited by 118 publications

References 0 publications

Persistence of type 5 adenovirus DNA in cells transformed by temperature-sensitive mutant, H5ts125.

Persistence of type 5 adenovirus DNA in cells transformed by temperature-sensitive mutant, H5ts125.

Temperature-sensitive replication of H5ts125 adenovirus DNA in vitro.

Protein Kinases Associated with the Adenovirus Single‐Stranded DNA‐Binding Protein

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