TCDD-inducible poly(ADP-ribose) polymerase: A novel response to 2,3,7,8-tetrachlorodibenzo-p-dioxin

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) causes pleotropic effects in mam malian species through modulating gene expression. Here we analyzed TCDD-in duced mRNA expression by using mRNA differential display and report the clo ning of a novel TCDD-inducible poly(ADP-ribose) polymerase (TiPARP). TiPARP cDNA contains an open reading frame of 657 amino acid residues; the carbox yl half shares sequence similarity to the catalytic domain of PARP, a famil y of enzymes that catalyze poly ADP-ribosylation of proteins. Expression of the cDNA by in vitro transcription/translation reveals a protein of simila r to 75 kDa. The expressed TiPARP exhibits PARP activity toward histone. Ti PARP is highly homologous to RM1 which is induced during long-term potentia tion, a memory formation process, and to TIL which is induced in T cells in filtrating progressing tumors. TiPARP mRNA is expressed in a broad range of mouse tissues. Together, these data demonstrate that TiPARP is a novel tar get of TCDD that may contribute to multiple responses to TCDD by modulating protein function through Poly ADP-ribosylation. (C) 2001 Elsevier Science.