Poly(ADP-ribose) polymerase-1 and its ambiguous role in cellular life and death

Authors:

Maria Castedo1,2, Antoine Lafarge1,2,3 and Guido Kroemer1,2,4
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Affiliations:

1 Equipe 11 labellisée par la Ligue contre le Cancer, Université de Paris Cité, Sorbonne Université, INSERM U1138, Centre de Recherche des Cordeliers, 75006 Paris, France.
2 Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Campus, Villejuif, France.
3 Faculté de médecine, Université de Paris Saclay, Kremlin Bicêtre, France.
4 Institut du Cancer Paris CARPEM, Department of Biology, Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris, Paris, France.

Keywords: 

PARP1 inhibition, DNA damage, parthanatos, cancer, neurological diseases, aging, cellular stress response.

Corresponding Author(s):

Maria Castedo, Equipe 11 labellisée par la Ligue contre le Cancer, Université de Paris, Sorbonne Université, INSERM U1138, Centre de Recherche des Cordeliers, 75006 Paris, France; maria.castedodelrieu@sorbonne-universite.fr Guido Kroemer, Equipe 11 labellisée par la Ligue contre le Cancer, Université de Paris, Sorbonne Université, INSERM U1138, Centre de Recherche des Cordeliers, 75006 Paris, France; kroemer@orange.fr

Conflict of interest statement:

GK has been holding research contracts with Daiichi Sankyo, Eleor, Kaleido, Lytix Pharma, PharmaMar, Sam-sara, Sanofi, Sotio, Vascage and Vasculox/Tioma. GK is on the Board of Directors of the Bristol Myers Squibb Foundation France. GK is a scientific co-founder of everImmune, Osasuna Therapeutics, Samsara Thera-peutics and Therafast Bio.

Please cite this article as:

Maria Castedo, Antoine Lafarge and Guido Kroemer (2023). Poly(ADP-ribose) polymerase-1 and its ambiguous role in cellular life and death. Cell Stress 7(1): 1-6. doi: 10.15698/cst2023.01.275

© 2023 Castedo et al. This is an open-access article released under the terms of the Creative Commons Attribution (CC BY) license, which allows the unrestricted use, distribution, and reproduction in any medium, provided the original author and source are acknowledged.

Abstract:

The deletion of the gene coding for poly(ADPribose) polymerase-1 (PARP1) or its pharmacological inhibition protects mice against cerebral ischemia and Parkinson’s disease. In sharp contrast, PARP1 inhibitors are in clinical use for the eradication of vulnerable cancer cells. It appears that excessive PARP1 activation is involved in a specific cell death pathway called parthanatos, while inhibition of PARP1 in cancer cells amplifies DNA damage to a lethal level. Hence, PARP1 plays a context-dependent role in cell fate decisions. In addition, it appears that PARP1 plays an ambiguous role in organismal aging.