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.