Poly(ADP-ribose) makes a date with death.
Poly(ADP-ribose) polymerase (PARP) enzymes catalyze the conversion of NAD(+) to polymers of poly(ADP-ribose) (PAR). Although its role in the DNA-damage response has long been recognized, recent work indicates that PAR itself acts at the mitochondria to directly induce cell death through stimulation of apoptosis-inducing factor (AIF) release. This review discusses PAR synthesis and degradation, and the role of PAR misregulation in various disease states. Attention is given to opportunities for therapeutic intervention with small molecules that are involved in PAR signaling, with specific focus on poly(ADP-ribose) glycohydrolase (PARG) and AIF.
Heeres
James T
JT
Department of Chemistry, Roger Adams Laboratory, University of Illinois, Urbana, IL 61801, USA.
Hergenrother
Paul J
PJ
D000818:Animals; D051033:Apoptosis Inducing Factor / Q000378:metabolism; D016923:Cell Death / Q000502:physiology*; D006801:Humans; D011064:Poly Adenosine Diphosphate Ribose / Q000378:metabolism*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D015398:Signal Transduction
D051033:Apoptosis Inducing Factor; D011064:Poly Adenosine Diphosphate Ribose; D011065:Poly(ADP-ribose) Polymerases