Differential interaction of temperature-sensitive simian virus 40 T antigens with tumor suppressors pRb and p53.
Previous studies have shown that simian virus 40 large T antigen transforms cells by binding and inactivating suppressors of cell cycle progression and tumor formation. Here, we characterize the interactions of five temperature-sensitive T antigens with the tumor suppressor proteins pRb and p53. All five mutant T antigens bind pRb at the nonpermissive temperature with efficiencies similar to that of wild-type T antigen. A single transformation-competent mutant, with a substitution of amino acid 186, binds p53 at the nonpermissive temperature. Four transformation-defective mutants, with a substitution at T antigen position 357, 422, 427, or 438, are temperature sensitive for the binding and inactivation of p53. Our findings provide a basis for understanding the behavior of cells transformed by temperature-sensitive T antigens.
Ray
S
S
Department of Molecular Genetics and Microbiology, State University of New York, Stony Brook, New York 11794-5222, USA.
Anderson
M E
ME
Tegtmeyer
P
P
D000818:Animals; D000957:Antigens, Viral, Tumor / Q000378:metabolism*; D006801:Humans; D016160:Retinoblastoma Protein / Q000378:metabolism*; D013539:Simian virus 40 / Q000378:metabolism*; D013696:Temperature; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D000957:Antigens, Viral, Tumor; D016160:Retinoblastoma Protein; D016159:Tumor Suppressor Protein p53