O. Cohausz C. Blenn M. Malanga F. R. Althaus +41 44 6358 910 fra@vetpharm.uzh.ch Institute of Pharmacology and Toxicology University of Zurich-Vetsuisse Winterthurerstrasse 260 8057 Zurich Switzerland Department of Functional and Structural Biology University Federico II of Naples Via Cinthia, Monte S. Angelo 80126 Napoli Italy Abstract. Poly(ADP-ribose) (PAR) has been identified as a DNA damage-inducible cell death signal upstream of apoptosis-inducing factor (AIF). PAR causes the translocation of AIF from mitochondria to the nucleus and triggers cell death. In living cells, PAR molecules are subject to dynamic changes pending on internal and external stress factors. Using RNA interference (RNAi), we determined the roles of poly(ADP-ribose) polymerases-1 and -2 (PARP-1, PARP-2) and poly(ADP-ribose) glycohydrolase (PARG), the key enzymes configuring PAR molecules, in cell death induced by an alkylating agent. We found that PARP-1, but not PARP-2 and PARG, contributed to alkylation-induced cell death. Likewise, AIF translocation was only affected by PARP-1. PARP-1 seems to play a major role configuring PAR as a death signal involving AIF translocation regardless of the death pathway involved.
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The roles of poly(ADP-ribose)-metabolizing enzymes in alkylation-induced cell death
O., Cohausz; C., Blenn; M., Malanga; F., Althaus
Follow Cellular and Molecular Life Sciences
, Volume 65 (4)
Springer Journals – Feb 1, 2008
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