Understanding specific functions of PARP-2: new lessons for cancer therapy.

Poly(ADP-ribosyl)ation (PARylation) is a widespread and highly conserved post-translational modification catalysed by a large family of enzymes called poly(ADP-ribose) polymerases (PARPs). PARylation plays an essential role in various cardinal processes of cellular physiology and recent approvals an...

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Authors: Ali, Syed O., Khan, Farhaan A., Galindo-Campos, Miguel A., Yélamos López, José
Format: article
Status:Published version
Publication Date:2016
Country:España
Institution:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repository:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:10230/28225
Online Access:http://hdl.handle.net/10230/28225
Access Level:Open access
Keyword:Poly(ADP-ribose) polymerases
Poly(ADP-ribosyl)ation
Cancer
Isoform-selective inhibition
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spelling Understanding specific functions of PARP-2: new lessons for cancer therapy.Ali, Syed O.Khan, Farhaan A.Galindo-Campos, Miguel A.Yélamos López, JoséPoly(ADP-ribose) polymerasesPoly(ADP-ribosyl)ationCancerIsoform-selective inhibitionPoly(ADP-ribosyl)ation (PARylation) is a widespread and highly conserved post-translational modification catalysed by a large family of enzymes called poly(ADP-ribose) polymerases (PARPs). PARylation plays an essential role in various cardinal processes of cellular physiology and recent approvals and breakthrough therapy designations for PARP inhibitors in cancer therapy have sparked great interest in pharmacological targeting of PARP proteins. Although, many PARP inhibitors have been developed, existing compounds display promiscuous inhibition across the PARP superfamily which could lead to unwanted off-target effects. Thus the prospect of isoform-selective inhibition is being increasingly explored and research is now focusing on understanding specific roles of PARP family members. PARP-2, alongside PARP-1 and PARP-3 are the only known DNA damage-dependent PARPs and play critical roles in the DNA damage response, DNA metabolism and chromatin architecture. However, growing evidence shows that PARP-2 plays specific and diverse regulatory roles in cellular physiology, ranging from genomic stability and epigenetics to proliferative signalling and inflammation. The emerging network of PARP-2 target proteins has uncovered wide-ranging functions of the molecule in many cellular processes commonly dysregulated in carcinogenesis. Here, we review novel PARP-2-specific functions in the hallmarks of cancer and consider the implications for the development of isoform-selective inhibitors in chemotherapy. By considering the roles of PARP-2 through the lens of tumorigenesis, we propose PARP-2-selective inhibition as a potentially multipronged attack on cancer physiology.The JY laboratory is supported by grants from Spanish Ministerio de Economía y Competitividad (SAF2014-53467-R), Fundació La Marató de TV3 (20134130), and CIBERehd.e-Century Publishing201720172016info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/28225reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésAmerican Journal of Cancer Research. 2016 Sep 1;6(9):1842-63AJCR Copyright © 2016info:eu-repo/semantics/openAccessoai:recercat.cat:10230/282252026-05-29T05:05:01Z
dc.title.none.fl_str_mv Understanding specific functions of PARP-2: new lessons for cancer therapy.
title Understanding specific functions of PARP-2: new lessons for cancer therapy.
spellingShingle Understanding specific functions of PARP-2: new lessons for cancer therapy.
Ali, Syed O.
Poly(ADP-ribose) polymerases
Poly(ADP-ribosyl)ation
Cancer
Isoform-selective inhibition
title_short Understanding specific functions of PARP-2: new lessons for cancer therapy.
title_full Understanding specific functions of PARP-2: new lessons for cancer therapy.
title_fullStr Understanding specific functions of PARP-2: new lessons for cancer therapy.
title_full_unstemmed Understanding specific functions of PARP-2: new lessons for cancer therapy.
title_sort Understanding specific functions of PARP-2: new lessons for cancer therapy.
dc.creator.none.fl_str_mv Ali, Syed O.
Khan, Farhaan A.
Galindo-Campos, Miguel A.
Yélamos López, José
author Ali, Syed O.
author_facet Ali, Syed O.
Khan, Farhaan A.
Galindo-Campos, Miguel A.
Yélamos López, José
author_role author
author2 Khan, Farhaan A.
Galindo-Campos, Miguel A.
Yélamos López, José
author2_role author
author
author
dc.subject.none.fl_str_mv Poly(ADP-ribose) polymerases
Poly(ADP-ribosyl)ation
Cancer
Isoform-selective inhibition
topic Poly(ADP-ribose) polymerases
Poly(ADP-ribosyl)ation
Cancer
Isoform-selective inhibition
description Poly(ADP-ribosyl)ation (PARylation) is a widespread and highly conserved post-translational modification catalysed by a large family of enzymes called poly(ADP-ribose) polymerases (PARPs). PARylation plays an essential role in various cardinal processes of cellular physiology and recent approvals and breakthrough therapy designations for PARP inhibitors in cancer therapy have sparked great interest in pharmacological targeting of PARP proteins. Although, many PARP inhibitors have been developed, existing compounds display promiscuous inhibition across the PARP superfamily which could lead to unwanted off-target effects. Thus the prospect of isoform-selective inhibition is being increasingly explored and research is now focusing on understanding specific roles of PARP family members. PARP-2, alongside PARP-1 and PARP-3 are the only known DNA damage-dependent PARPs and play critical roles in the DNA damage response, DNA metabolism and chromatin architecture. However, growing evidence shows that PARP-2 plays specific and diverse regulatory roles in cellular physiology, ranging from genomic stability and epigenetics to proliferative signalling and inflammation. The emerging network of PARP-2 target proteins has uncovered wide-ranging functions of the molecule in many cellular processes commonly dysregulated in carcinogenesis. Here, we review novel PARP-2-specific functions in the hallmarks of cancer and consider the implications for the development of isoform-selective inhibitors in chemotherapy. By considering the roles of PARP-2 through the lens of tumorigenesis, we propose PARP-2-selective inhibition as a potentially multipronged attack on cancer physiology.
publishDate 2016
dc.date.none.fl_str_mv 2016
2017
2017
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10230/28225
url http://hdl.handle.net/10230/28225
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv American Journal of Cancer Research. 2016 Sep 1;6(9):1842-63
dc.rights.none.fl_str_mv AJCR Copyright © 2016
info:eu-repo/semantics/openAccess
rights_invalid_str_mv AJCR Copyright © 2016
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv e-Century Publishing
publisher.none.fl_str_mv e-Century Publishing
dc.source.none.fl_str_mv reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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