The poly(ADP-ribose) polymerases (PARPs): new roles in intracellular transport

Post-transcriptional modification of proteins is crucial for balancing protein structure and function in many biological processes. The addition of polymers of adenosine diphosphate (ADP)-ribose (PAR), which are synthesized by PAR polymerases (PARPs) from nicotinamide adenine dinucleotide (NAD), is one such distinctive post-translational modification. PARP-1, the best characterized of the 17-member PARP family, is considered a key isoform responsible for poly(ADP-ribosyl)ation of several nuclear proteins. ADP-ribose polymers add a highly negative charge to their target proteins, resulting in a modification of their activities and functions. PARPs not only participate in regulating cell survival and cell death programs, but are also involved in other biological functions with which novel members of the PARP family have been shown to be involved. Among such functions are transcription regulation, telomere cohesion and mitotic spindle formation during cell division, and intracellular energy metabolism. Recent work from our laboratory and others has highlighted the novel role of PARP-1 in regulating the intracellular trafficking of key cellular proteins such as p53 and nuclear factor-kappa B (NF-κB). Recent literature has revealed that ADP-ribosylation reactions may play important roles in cellular trafficking during inflammation, cell death, and DNA repair. This review will summarize recent findings and concepts linking the role of PARP enzymes and their poly-ADP-ribosylation activity in the regulation of intracellular transport processes. A special focus is placed on the proposed molecular mechanisms involved in such transport processes as the functional significance of PARylation of p53, NF-κB, and high-mobility group protein box 1.