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Sci. Signal., 5 April 2011
Vol. 4, Issue 167, p. ra20
Scoring a PAR on Deaths Course
Overactivation of the DNA repair enzyme PARP-1 [poly(ADP-ribose) (PAR) polymerase-1] leads to "parthanatos," a form of cell death that is distinct from apoptosis and necrosis and that depends on release of apoptosis-inducing factor (AIF) from mitochondria. Here, Wang et al. showed that PAR bound directly to AIF, disrupting AIFs association with the mitochondria and allowing it to translocate to the nucleus to mediate cell death. Moreover, mutation of the PAR binding site of AIF enabled the authors to separate AIFs role in parthanatos from its function in mitochondrial respiration. Identification of AIF as a PAR-binding protein could potentially lead to the development of compounds that inhibit this interaction, protecting against parthanatos, or compounds that mimic it and thereby promote parthanatos as an agent of death in malignant cells.
Citation: Y. Wang, N. S. Kim, J.-F. Haince, H. C. Kang, K. K. David, S. A. Andrabi, G. G. Poirier, V. L. Dawson, T. M. Dawson, Poly(ADP-Ribose) (PAR) Binding to Apoptosis-Inducing Factor Is Critical for PAR Polymerase-1–Dependent Cell Death (Parthanatos). Sci. Signal.4, ra20 (2011).