Abstract
PARP-1 (poly(ADP-ribose)-polymerase 1), mainly known for its protective role in DNA repair, also regulates inflammatory processes. Notably, defects in DNA repair and chronic inflammation may both predispose to cancer development. On the other hand, inhibition of DNA repair and inflammatory responses can be beneficial in cancer therapy and PARP inhibitors are currently used for their lethal effects on tumor cells. Furthermore, excess of PARP-1 activity has been associated with many tumors and inflammation-related clinical conditions, including asthma, sepsis, arthritis, atherosclerosis, and neurodegenerative diseases, to name a few. Activation and inhibition of PARP represent, therefore, a double-edged sword that can be exploited for therapeutic purposes. In our review, we will discuss recent findings highlighting the composite multifaceted role of PARP-1 in cancer and inflammation-related diseases.
Highlights
Poly(ADP-ribose)-polymerases (PARPs), more recently named ADP-ribosyl-transferase diphtheria toxin-like (ARTDs), belong to an ancient evolutionary-conserved family of proteins involved in abiotic and biotic stress responses, DNA repair, cell death, division, and differentiation, as well as in inflammation and immune responses
NAD+ mimetics differing in specificity and potency that bind to the NAD+ site in the catalytic domain of PARP-1, preventing PARylation through catalytic inhibition
PARP-1 belongs to the DNA-dependent nuclear PARPs group whose catalytic
Summary
Poly(ADP-ribose)-polymerases (PARPs), more recently named ADP-ribosyl-transferase diphtheria toxin-like (ARTDs), belong to an ancient evolutionary-conserved family of proteins involved in abiotic and biotic stress responses, DNA repair, cell death, division, and differentiation, as well as in inflammation and immune responses. By mean of poly-ADP-ribosylation (PARylation), PARP-1 negatively regulates its own enzymatic activity [6] and modifies functions of acceptor proteins due to the high negative charge and complexity of ADP-ribose polymers (PARs) [3]. PARP-1 regulates target proteins through enzymatic modifications and by acting as a docking molecule. This occurs for transcription factors as it is the case of NF-κB [7], a transcription factor family linking PARP-1, DNA repair, and inflammation. PARP-1 regulates gene expression under basal as well as signal- and stress-activated conditions, at multiple levels: chromatin structure, methylation pattern, enhancer-binding, promoter co-regulation, activation of transcription factors, insulation, and post-transcriptional RNA modifications [13,14,15]. A brief account of PARPis counteracting the unwarranted activation of PARP-1 in cancer and non-cancer diseases and the consequent potential oncogenic risk of PARP inactivation is discussed
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
