SV40 T-antigen as a dual oncogene: structure and function of the plasma membrane-associated population.
SV40 T-antigen (T-ag) is localized in both the nucleus (nT-ag) and plasma membrane (pmT-ag) of cells and provides multiple functions necessary for cell transformation. The pmT-ag population is structurally very similar to the nT-ag. Transport to the cell surface is by an unknown mechanism that does not involve the secretory pathway. The disposition of T-ag in the membrane exposes both the amino and the carboxyl terminus on the exterior of the cell. Nuclear-transport-defective mutants of T-ag can transform established cells in culture, but not primary cells, suggesting that non-nuclear forms of T-ag may mediate some transformation-related process(es). A non-cytolytic protein extraction technique utilizing 1-butanol solubilized from SV40-transformed cells a multimeric complex composed of pmT-ag and at least five cellular proteins ranging in size from 35,000 (35K) to 60K M. Both amino- and carboxylterminal T-ag-specific monoclonal antibodies co-precipitated T-ag and the 35-60K Mr proteins, but antibodies against the internal portion of T-ag precipitated only uncomplexed T-ag. The growth state of the cells markedly influenced the expression of the T-ag-containing surface complexes; more complexes were recovered from actively dividing cells than from confluent cell cultures, and suspension cells yielded more complexes than cells on a substratum. The complex exhibited a highly dynamic association with the cell membrane, as demonstrated by pulse-chase analysis. The characteristics of growth-dependent expression and rapid turnover rate suggest a functional role for the membrane complex. The identities of the cellular proteins in the complex with pmT-ag are unknown, although one member (56K) is recognized by p53-specific monoclonal antibodies.
Butel
J S
JS
Division of Molecular Virology, Baylor College of Medicine, Houston, Texas 77030.
Jarvis
D L
DL
Maxwell
S A
SA
D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000235:genetics*; D002462:Cell Membrane / Q000276:immunology; D002471:Cell Transformation, Neoplastic; D006801:Humans; D009857:Oncogenes; D013539:Simian virus 40 / Q000235:genetics* / Q000276:immunology
D000952:Antigens, Polyomavirus Transforming