Modification of SV40 T antigen by poly ADP-ribosylation.
The SV40 large T antigen is a multifunctional protein presumed to represent a single translation product of the early viral genes. A wide range of biological controls including the regulation of viral DNA replication, transcription and cell transformation has been attributed to T antigen. Previous evidence has indicated that large T antigen is modified in at least two ways, N-terminal acetylation and amino acid phosphorylation. In this study, we demonstrate a novel modification of a population of SV40 T antigen molecules by poly ADP-ribosylation. The covalent linkage of this oligonucleotide side chain to large T antigen, but not small t antigen, was demonstrated in experiments in which SV40-infected cells were labeled in vivo with 32P-orthophosphate or 14C-adenosine. Treatment of this labeled T antigen with snake venom phosphodiesterase released iso-ADP-ribose or treatment with ADP-ribose glycohydrolase released ADP-ribose. A method has been developed for the in vitro ADP-ribosylation of T antigen present in an infected cell nuclear extract with radiolabeled NAD. Since this type of modification is known to affect enzyme activity, its presence on T antigen suggests a similar role in the regulation of certain biological functions under the control of this protein.
D000818:Animals; D000951:Antigens, Neoplasm / Q000378:metabolism*; D000956:Antigens, Viral / Q000378:metabolism*; D000957:Antigens, Viral, Tumor; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D008970:Molecular Weight; D009243:NAD / Q000378:metabolism; D009702:Nucleoside Diphosphate Sugars / Q000378:metabolism*; D011064:Poly Adenosine Diphosphate Ribose / Q000378:metabolism*
D000951:Antigens, Neoplasm; D000956:Antigens, Viral; D000957:Antigens, Viral, Tumor; D009702:Nucleoside Diphosphate Sugars; D009243:NAD; D011064:Poly Adenosine Diphosphate Ribose