Simian virus 40 gene A function and maintenance of transformation

Abstract

Transformants have been isolated after infection of rat embryo cells at 33 C with either wild-type simian virus 40 or with the temperature-sensitive gene A mutants, tsA7 and tsA28. Examination of properties usually associated with transformation such as growth in 1% serum, growth rate, saturation density, and morphology show that these properties are temperature dependent in the tsA transformants characterized, but are not temperature dependent in the wild-type transformants that have been examined. In the most thoroughly characterized tsA transformants the expression of T antigen also appears to be temperature dependent. These data suggest that an active A function is required for the maintenance of transformation in these cells. In the lytic cycle, the A function is involved in the initiation of DNA synthesis. Thus transformation by simian virus 40 may be the direct consequence of the introduction of the simian virus 40 replicon and the presence of its DNA initiator function, which causes the cell to express a transformed phenotype.

Subcellular distribution of simian virus 40 T antigen species in various cell lines: The 56K protein

“…The functions of these protein antigens are under intense investigation. Large T Ag binds to DNA (Jessel et al, 1975(Jessel et al, , 1976Tenen et al, 1975;Carroll et al, 1974a,b); this 94K dalton species in the nucleus is thought to be responsible for initiation of DNA synthesis (Kriegler et al, 1978;Jessel el al., 1976;Reed et al, 1975;Tegtmeyer, 1972) and induction and maintenance of the transformed state of the cell (Brugge and Butel, 1975;Martin and Chou, 1975;Osborne and Weber, 1975;Tegtmeyer, 1975). It has previously been shown (Anderson et al, 1977a,b, Chang et al, 1979aLuborsky et al, 1978) that partially purified SV40 T antigen preparations contain tumor-specific transplantation and surface antigen activities (TSTA and TSSA).…”

Detection of simian virus 40 surface‐associated large tumor antigen by enzyme‐catalyzed radioiodination

“…Cells either infected or transformed by tsA mutants of SV40, with few exceptions, express immunologically reactive nuclear T-ag at the nonpermissive temperature (Brugge and Butel, 1975;Osborn and Weber, 1975;Tegtmeyer, 1975;Noonan and Butel, 1978;Alwine and Khoury, 1980), indicating that the tsA lesion does not preclude transport of mutant T-ag to the nucleus. Since tsA T-ag was observed on the surface of tsA-infected cells at the nonpermissive temperature by surface iodination, it appears that transport of the molecule to the cell surface is likewise not abolished by the tsA lesion.…”

“…Members of one class of SV40 temperature-sensitive mutants map in the A cistron (tsA mutants) and exhibit altered thermal stability of immunological and biological properties of T-ag (Carroll et al, 1974;Alwine et al, 1975;Jessel et al, 1975;Tenen et al, 1975). The tsA mutants transform cells at a reduced efficiency at the nonpermissive temperature (Kimura and Dulbecco, 1972;Tegtmeyer, 1972) and most cells transformed at the permissive temperature by the tsA viruses are temperature-sensitive for many growth-related properties associated with the transformed phenotype (Brugge and Butel, 1975;Kimura and Itagaki, 1975;Martin and Chou, 1975;Osborn and Weber, 1975;Tegtmeyer, 1975). The role of small t-ag in cellular transformation is less clear.…”

In vivo and in vitro TSTA‐inducing activity of temperature‐sensitive (TS) mutants of SV40

“…With the use of SV40 ts A mutants, data demonstrating the necessity of A gene function for the maintenance of the transformed state have been presented (Tegtmeyer, 1975 ;Osborn and Weber, 1975;Martin and Chou, 1975;Brugge and Butel, 1975). Butel et al (1975) discovered that the expression of the S antigen in cells transformed with ts A mutants is temperature-dependent and that this antigen is not expressed at the non-permissive temperature.…”