A Retroviral Promoter is Sufficient to Convert Proto-src to a Transforming Gene That is Distinct from the Src Gene of Rous Sarcoma Virus

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 1990 Dec 1

PMID 2174554

Citations 3

Authors

H Zhou

P H Duesberg

Affiliations

Soon will be listed here.

Abstract

The src genes of four natural isolates of avian sarcoma viruses differ from cellular proto-src in two genetic substitutions: the promoter of the cellular gene is replaced by a retroviral counterpart, and at least six codons from the 3' terminus are replaced by retroviral or heterologous cell-derived elements. Since virus constructs with a complete proto-src coding region failed to transform avian cells but acquired transforming function by point mutations of various codons, it has been proposed that point mutation is sufficient to convert proto-src to a transforming gene. However, promoter substitution is sufficient to convert two other proto-onc genes, proto-ras and proto-myc, to retroviral transforming genes. In view of this, we have reexamined whether promoter substitution, point mutation, or both are necessary to convert proto-src into a retroviral transforming gene. It was found that a recombinant virus (RpSV), in which the src gene of Rous sarcoma virus (RSV) was replaced by the complete coding region of proto-src, transformed quail and chicken embryo cells. The oncogene of RpSV differs from the src gene of RSV in three genetic properties: (i) it is weaker--e.g., transformed cells are flatter; (ii) it is slower--e.g., focus formation takes 9 to 12 days compared to 4 days for RSV; and (iii) its host range is narrower than that of RSV--e.g., only subsets of heterogeneous embryo cells are transformed by RpSV even after weeks or months. Replacement of the proto-src 3' terminus of RpSV by that of src from RSV generates a recombinant virus (RpvSV) that equals RSV in transforming function. It is concluded that a retroviral promoter, naturally substituted via illegitimate recombination with retroviruses, is sufficient to convert at least three proto-onc genes, src, myc, and ras, to retroviral transforming genes.

Citing Articles

Dominant transformation by mutated human ras genes in vitro requires more than 100 times higher expression than is observed in cancers.

Hua V, Wang W, Duesberg P Proc Natl Acad Sci U S A. 1997; 94(18):9614-9.

PMID: 9275171 PMC: 23234. DOI: 10.1073/pnas.94.18.9614.

Avian erythroblastosis virus E26: only one (myb) of two cell-derived coding regions is necessary for oncogenicity.

Wu Y, Duesberg P Proc Natl Acad Sci U S A. 1994; 91(9):4039-43.

PMID: 8171032 PMC: 43718. DOI: 10.1073/pnas.91.9.4039.

Unmutated proto-src coding region is tumorigenic if expressed from the promoter of Rous sarcoma virus: implications for the gene-mutation hypothesis of cancer.

Wu Y, Zhou H, Duesberg P Proc Natl Acad Sci U S A. 1992; 89(14):6393-7.

PMID: 1321438 PMC: 49507. DOI: 10.1073/pnas.89.14.6393.

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