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Beyond DNA Repair: Additional Functions of PARP-1 in Cancer
Poly(ADP-ribose) polymerases (PARPs) are DNA-dependent nuclear enzymes that transfer negatively charged ADP-ribose moieties from cellular nicotinamide-adenine-dinucleotide (NAD(+)) to a variety of protein substrates, altering protein–protein and protein-DNA interactions. The most studied of these en...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2013
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3841914/ https://www.ncbi.nlm.nih.gov/pubmed/24350055 http://dx.doi.org/10.3389/fonc.2013.00290 |
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author | Weaver, Alice N. Yang, Eddy S. |
author_facet | Weaver, Alice N. Yang, Eddy S. |
author_sort | Weaver, Alice N. |
collection | PubMed |
description | Poly(ADP-ribose) polymerases (PARPs) are DNA-dependent nuclear enzymes that transfer negatively charged ADP-ribose moieties from cellular nicotinamide-adenine-dinucleotide (NAD(+)) to a variety of protein substrates, altering protein–protein and protein-DNA interactions. The most studied of these enzymes is poly(ADP-ribose) polymerase-1 (PARP-1), which is an excellent therapeutic target in cancer due to its pivotal role in the DNA damage response. Clinical studies have shown susceptibility to PARP inhibitors in DNA repair defective cancers with only mild adverse side effects. Interestingly, additional studies are emerging which demonstrate a role for this therapy in DNA repair proficient tumors through a variety of mechanisms. In this review, we will discuss additional functions of PARP-1 – including regulation of inflammatory mediators, cellular energetics and death pathways, gene transcription, sex hormone- and ERK-mediated signaling, and mitosis – and the role these PARP-1-mediated processes play in oncogenesis, cancer progression, and the development of therapeutic resistance. As PARP-1 can act in both a pro- and anti-tumor manner depending on the context, it is important to consider the global effects of this protein in determining when, and how, to best use PARP inhibitors in anticancer therapy. |
format | Online Article Text |
id | pubmed-3841914 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-38419142013-12-13 Beyond DNA Repair: Additional Functions of PARP-1 in Cancer Weaver, Alice N. Yang, Eddy S. Front Oncol Oncology Poly(ADP-ribose) polymerases (PARPs) are DNA-dependent nuclear enzymes that transfer negatively charged ADP-ribose moieties from cellular nicotinamide-adenine-dinucleotide (NAD(+)) to a variety of protein substrates, altering protein–protein and protein-DNA interactions. The most studied of these enzymes is poly(ADP-ribose) polymerase-1 (PARP-1), which is an excellent therapeutic target in cancer due to its pivotal role in the DNA damage response. Clinical studies have shown susceptibility to PARP inhibitors in DNA repair defective cancers with only mild adverse side effects. Interestingly, additional studies are emerging which demonstrate a role for this therapy in DNA repair proficient tumors through a variety of mechanisms. In this review, we will discuss additional functions of PARP-1 – including regulation of inflammatory mediators, cellular energetics and death pathways, gene transcription, sex hormone- and ERK-mediated signaling, and mitosis – and the role these PARP-1-mediated processes play in oncogenesis, cancer progression, and the development of therapeutic resistance. As PARP-1 can act in both a pro- and anti-tumor manner depending on the context, it is important to consider the global effects of this protein in determining when, and how, to best use PARP inhibitors in anticancer therapy. Frontiers Media S.A. 2013-11-27 /pmc/articles/PMC3841914/ /pubmed/24350055 http://dx.doi.org/10.3389/fonc.2013.00290 Text en Copyright © 2013 Weaver and Yang. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Oncology Weaver, Alice N. Yang, Eddy S. Beyond DNA Repair: Additional Functions of PARP-1 in Cancer |
title | Beyond DNA Repair: Additional Functions of PARP-1 in Cancer |
title_full | Beyond DNA Repair: Additional Functions of PARP-1 in Cancer |
title_fullStr | Beyond DNA Repair: Additional Functions of PARP-1 in Cancer |
title_full_unstemmed | Beyond DNA Repair: Additional Functions of PARP-1 in Cancer |
title_short | Beyond DNA Repair: Additional Functions of PARP-1 in Cancer |
title_sort | beyond dna repair: additional functions of parp-1 in cancer |
topic | Oncology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3841914/ https://www.ncbi.nlm.nih.gov/pubmed/24350055 http://dx.doi.org/10.3389/fonc.2013.00290 |
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