Identification of the ADP-Ribosylation Sites in the PARP-1 Automodification Domain: Analysis and Implications

摘要

The protein poly(ADP-ribosyl)ation reaction, where ADP-ribose polymers are attached to acceptor proteins (see Figure 1), is a unique posttranslational modification that affects many cellular processes and diseases including reperfusion injury, acute CNS disorders, inflammatory diseases, diabetes, cancers, etc. Most cellular poly-(ADP-ribosyl)ation reactions are catalyzed by poly(ADP-ribose) polymerase-1 (PARP-1), whose function is activated by binding with nicked DNA. Following its activation, PARP-1 modifies many nuclear proteins including histones, DNA repair enzymes, transcription factors, and even itself. PARP-1 can be dissected into six domains (domains A-F, see Figure 1) based on homology with identified functional modules.