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PMID: 6308607 Published · ppublish English Comparative Study Journal Article Research Support, U.S. Gov't, P.H.S.

Structure and biological activity of v-raf, a unique oncogene transduced by a retrovirus.

Rapp UR, Goldsborough MD, Mark GE, Bonner TI, Groffen J, Reynolds FH, Stephenson JR

Abstract

We have molecularly cloned a unique acutely transforming replication-defective mouse type C virus (3611-MSV) and characterized its acquired oncogene. The viral genome closely resembles Moloney (M) murine leukemia virus (MuLV), except for a substitution in M-MuLV in the middle of p30 and the middle of the polymerase gene (pol). Heteroduplex analysis revealed that 2.4 kilobases of M-MuLV DNA were replaced by 1.2 kilobases of cellular DNA. The junctions between viral and cellular sequences were determined by DNA sequence analysis to be 517 nucleotides into the p30 sequence and 1,920 nucleotides into the polymerase sequence. Comparison of the transforming gene from 3611-MSV, designated v-raf, with previously isolated retrovirus oncogenes either by direct hybridization or by comparison of restriction fragments of their cellular homologs shows it to be unique. Transfection of NIH 3T3 cells with cloned 3611-MSV proviral DNA leads to highly efficient transformation and the recovered virus elicits tumors in mice typical of the 3611-MSV virus. Transfected NIH 3T3 cells express two 3611-MSV-specific polyproteins (P75 and P90), both of which contain NH2-terminal gag gene-encoded components linked to the acquired sequence (v-raf) translational product. The cellular homolog, c-raf, is present in one or two copies per haploid genome in mouse and human DNA.

MeSH Terms
Animals Cell Line Cells, Cultured Cloning, Molecular DNA Restriction Enzymes DNA, Viral/genetics Leukemia Virus, Murine/genetics Mice Moloney murine leukemia virus/genetics Mutation Oncogenes Rats Retroviridae/genetics Sarcoma Viruses, Murine/genetics Species Specificity Transduction, Genetic
Chemicals
DNA, Viral DNA Restriction Enzymes
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Rapp U R
Goldsborough M D
Mark G E
Bonner T I
Groffen J
Reynolds F H
Stephenson J R
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39 references, click to expand
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
Published
1983-07-00
Pages
4218-22
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC384008
Subset
IM
Grants
NCI NIH HHS · N01-CO-75380 · United States
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