Regulation of tumor antigen synthesis by simain virus 40 gene A

Abstract

Simian virus 40 gene A has previously been shown to promote the replication of viral DNA and the transcription of late viral RNA in productive infection and to maintain the growth characteristics of some transformed cells. The present study examines the effect of the A function on proteins synthesized during productive and transforming infections. Under restrictive conditions, temperature-sensitive A mutants induce the overproduction of a 100,000-dalton protein both in productively infected monkey cells and in transformed rabbit cells. Immunoprecipitation of the induced protein with antisera, prepared against simian virus 40-induced tumors in hamsters, was used to identify the induced protein as tumor antigen. The same protein can be precipitated from extracts of cells infected by wild-type virus but not from uninfected cells. Furthermore, the mutant-induced protein is more rapidly degraded in vivo and is less tightly bound to intranuclear components than the protein induced by wild-type virus. The presence of the same virus-induced protein in infected cells from different species and the altered behavior of that protein in mutant infection strongly suggest that the protein is virus coded. Because the protein is large enough to account for the entire coding capacity in the early region of the simian virus 40 genome, the 100,000-dalton protein may well be the primary product of the only early gene identified by complementation studies, the A gene. If the 100,000-dalton protein that is overproduced in mutant infection is the A protein and the only early protein, then functional wild-type A protein must regulate its own synthesis in both productive and transforming infections.

Transformation of Mouse Peritoneal Macrophages and Bone Marrow Cells by Simian Virus 40

“…Alternatively, the expression of SV40 T-antigen may be affected by the functional cellular states specific to macrophages. It has been postulated that synthesis and appearance of SV40 T-antigen are regulated by its own synthesis (29), by the SV40 D protein (21,24) by the cyclic nucleotide system (22) and by cultural conditions (23). It is generally considered that cell growth is inconsistent with differentiated cell function.…”

Immunogenic properties of a soluble tumor rejection antigen (TSTA) from a simian virus 40‐induced sarcoma

“…Recently T-ag from SV40 has been immunoprecipitated and shown to have a mol. wt of approximately 100,ooO daltons (Tegtmeyer et al, 1975;Livingston et al, 1974). Since a protein of this size accounts for the entire coding capacity of the early region (A gene) of the viral genome, the implication is that T-ag and TSTA are structural antigens of this polypeptide chain.…”

Polyoma genome transcription in transformed mouse cells growing in culture and as tumors in syngeneic mice

“…A portion of the genome of this size contains enough information to code for a polypeptide with a molecular weight of approximately 40,000. Current estimates of the molecular weight of T antigen are in the range of 70,000-100,000 daltons (Del Villano and Defendi, 1973;Tegtmeyer et al, 1975). Since both the PY AL/N cells and the concanavalin-A-selected revertant are T-antigen-positive, it is necessary to resolve the apparent discrepancy between the proportion of the polyoma genome transcribed and the size of T antigen.…”