Human-Proto-Oncogene Nucleotide Sequences Corresponding to the Transforming Region of Simian Sarcoma Virus

Abstract

The nucleotide sequences of the six regions within the normal human cellular locus (c-sis) that correspond to the entire transforming region of the simian sarcoma virus (SSV) genome (v-sis) were determined. The regions are bounded by acceptor and donor splice sites and, except for region 6, resemble exons. Region 6 lacks a 3' donor splice site and terminates -5 base pairs from the 3' v-sis-helper-viral junction. This is consistent with a model proposing that SSV was generated by recombination between proviral DNA of a simian sarcoma associated virus and proto-sis and that introns were spliced out subsequently from a fused viral-sis messenger RNA. This also suggests that the 3' recombination occurred within an exon of the woolly monkey (Lagothrix) genome. The open reading frames predicting the v-sis and c-sis gene products coincide with the stop codon of c-sis located 123 nucleotides into the fifth region of homology. The overall nucleotide homology was 91 percent with substitutions mainly in the third codon positions within the open reading frame and with greatest divergence within the untranslated 3' portion of the sequences. The predicted protein products for v-sis and c-sis are 93 percent homologous. The predicted c-sis gene product is identical in 31 of 31 amino acids to one of the published sequences of platelet-derived growth factor. Thus, c-sis encodes one chain of human platelet-derived growth factor.

Highly purified fibroblast-derived growth factor, an SV40-transformed fibroblast-secreted mitogen, is closely related to platelet-derived growth factor.

“…To determine whether FDGF production represents the activation of a gene encoding PDGF in the SV28 line, poly(A)+ mRNA was isolated from SV28 and control cells, and hybridisations carried out using a DNA probe incorporating the region of the SSV oncogene (v-sis) which is almost identical to the Bchain of human PDGF Josephs et al, 1984;Chiu et al, 1984;Johnsson et al, 1984). Although v-sis is most closely related to sequences present in New World primates, it is derived from the highly conserved cellular c-sis gene, which occurs in a diverse range of mammalian species .…”

“…Similar observations with one glioma (Westermark and Wasteson, 1975;Heldin et al, 1980;Nister et al, 1982) and two sarcoma cell lines (Betsholtz et al, 1983;Nister et al, 1984) led to the same conclusions. Direct evidence has now established that the sis oncogene of simian sarcoma virus (SSV) encodes a protein which is structurally almost identical to the B-chain of PDGF Doolittle et al, 1983;Josephs et al, 1984;Chiu et al, 1984;Johnsson et al, 1984) and it is clear that cells transformed with this virus produce a factor(s) with some properties of PDGF Niman, 1984;Owen et al, 1984;Thiel and Hafenrichter, 1984;Niman et al, 1984). However this and other PDGF-like factors from various cell lines (Bourne and Rozengurt, 1976;Heldin et al, 1980;Betsholtz et al, 1983;Nister et al, 1984;BowenPope et al, 1984;Seifert et al, 1984;DiCorleto, 1984) have not been purified to homogeneity to establish their degree of similarity to PDGF.…”

Chondroprotective Effects of Taurine in Primary Cultures of Human Articular Chondrocytes

“…Moreover, the expression of collagen type X also disfavors further implantation, because its expression precedes the onset of endochondral ossification (Kwan et al 1997). One solution is the use of growth factors, but the application of growth factors in clinics is limited due to the following reasons: 1) growth factors may induce the formation of osteophyte, resulting in degeneration of articular cartilage (Hsieh et al 2003); 2) they may lead to tumorigenesis (Waterfield et al 1983;Josephs et al 1984;Downward et al 1984); and 3) they are generally expensive. Therefore, it is of significance to find other substance to substitute for growth factors in the restoration of defect.…”

Structural and functional aspects of platelet-derived growth factor

“…The PDGF B chain is almost identical to p28si q the transforming protein of simian sarcoma virus (SSV) (Waterfield et al, 1983;Doolittle et al, 1983; see further below). Analyses of cDNAs of the A (Betsholtz et al, 1986b) and the B (Josephs et al, 1984;Collins et al, 1985: Rao et al, 1986 figure). The dimers are held together by disulphide bonds.…”