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

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dc.contributor.author Ali, Syed O.
dc.contributor.author Khan, Farhaan A.
dc.contributor.author Galindo-Campos, Miguel A.
dc.contributor.author Yélamos López, José
dc.date.accessioned 2017-03-14T12:07:41Z
dc.date.available 2017-03-14T12:07:41Z
dc.date.issued 2016
dc.identifier.citation Ali SO, Khan FA, Galindo-Campos MA, Yélamos J. Understanding specific functions of PARP-2: new lessons for cancer therapy. Am J Cancer Res. 2016 Sep 1;6(9):1842-1863.
dc.identifier.issn 2156-6976
dc.identifier.uri http://hdl.handle.net/10230/28225
dc.description.abstract 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.
dc.description.sponsorship 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.
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher e-Century Publishing
dc.relation.ispartof American Journal of Cancer Research. 2016 Sep 1;6(9):1842-63
dc.rights AJCR Copyright © 2016
dc.title Understanding specific functions of PARP-2: new lessons for cancer therapy.
dc.type info:eu-repo/semantics/article
dc.subject.keyword Poly(ADP-ribose) polymerases
dc.subject.keyword Poly(ADP-ribosyl)ation
dc.subject.keyword Cancer
dc.subject.keyword Isoform-selective inhibition
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/publishedVersion

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