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The Role of PARPs in Cancer and Aging
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The Role of PARPs in Cancer and Aging

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Endocrinology and Metabolism".

Deadline for manuscript submissions: closed (28 February 2023) | Viewed by 8679

Special Issue Editors

Dr. Agnieszka Zdzislawa Robaszkiewicz

E-Mail Website
Guest Editor
Department of General Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, 90-236 Lodz, Poland
Interests: transcription; epigenetics; PARP1; SWI/SNF; EP300; differentiation; cancerogenesis; chromatin; transcription factors; transcription co-factors
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Andre Tremblay

E-Mail Website1 Website2
Guest Editor
Department of Biochemistry and Molecular Medicine, and Department of Obstetrics & Gynecology, Faculty of Medicine, University of Montreal, Montréal, QC H3T 1J4, Canada
Interests: nuclear receptor; transcription factor; cellular kinase pathway; estrogen receptor; upstream cellular signals; PPARs
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

PARP family members have been attracting the attention of researchers and clinicians due to the involvement of these proteins in a variety of intracellular processes, deregulation of which leads to pathological conditions. The contribution of PARPs to the development and progression of numerous diseases has been documented in the literature. Particular attention has been paid to the role of PARPs in cancer since the most frequently referred member of the family—PARP1—is responsible for the synthesis of approximately 80% of poly-ADP-ribose polymers under a stress condition, which are functionally linked with DNA repair. Changes in DNA structure, but also posttranslational modifications of PARPs and interaction with other proteins, lead to activation of mono- and poly-ADP-ribosylases, which affect metabolism, gene transcription, signaling cascades, and many other aspects. DNA damage frequently results from redox shift to an oxidative condition, which occurs in rapidly proliferating cancer cells but also accompanies senescence, but the two mentioned conditions are characterized by other alterations that induce PARP activity.

Our Special issue covers aspects regarding all factors that trigger enzymatically active PARPs, role of mono- and poly-ADP-ribosylation in cancer and aging, but also the contribution of non-enzymatic PARP family members to the two processes. We also invite submissions describing new concepts for the use of PARP inhibitors in anti-aging and anticancer approaches.

Dr. Agnieszka Zdzislawa Robaszkiewicz
Prof. Dr. Andre Tremblay
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

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Keywords

  • PARPs
  • Cancer
  • Aging
  • ADP-ribosylation
  • PARP inhibitors
  • Redox imbalance
  • DNA damage and repair
  • Transcription
  • Signaling
  • Metabolism

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Published Papers (2 papers)

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19 pages, 3611 KiB  
Article
Attenuation of Tumor Burden in Response to Rucaparib in Lung Adenocarcinoma: The Contribution of Oxidative Stress, Apoptosis, and DNA Damage
by Maria Pérez-Peiró, Paula Valentí-Serra, Blanca León-González, Coral Ampurdanés, Xavier Duran, José Yélamos and Esther Barreiro
Int. J. Mol. Sci. 2023, 24(3), 2580; https://doi.org/10.3390/ijms24032580 - 30 Jan 2023
Cited by 5 | Viewed by 2201
Abstract
In cancer, overactivation of poly (ADPribose) polymerases (PARP) plays a relevant role in DNA repair. We hypothesized that treatment with the PARP inhibitor rucaparib may reduce tumor burden via several biological mechanisms (apoptosis and oxidative stress) in mice. In lung tumors (LP07 lung [...] Read more.
In cancer, overactivation of poly (ADPribose) polymerases (PARP) plays a relevant role in DNA repair. We hypothesized that treatment with the PARP inhibitor rucaparib may reduce tumor burden via several biological mechanisms (apoptosis and oxidative stress) in mice. In lung tumors (LP07 lung adenocarcinoma) of mice treated/non-treated (control animals) with PARP inhibitor (rucaparib,150 mg/kg body weight/24 h for 20 day), PARP activity and expression, DNA damage, apoptotic nuclei, cell proliferation, and redox balance were measured using immunoblotting and immunohistochemistry. In lung tumors of rucaparib-treated mice compared to non-treated animals, tumor burden, PARP activity, and cell proliferation decreased, while DNA damage, TUNEL-positive nuclei, protein oxidation, and superoxide dismutase content (SOD)2 increased. In this experiment on lung adenocarcinoma, the pharmacological PARP inhibitor rucaparib elicited a significant improvement in tumor size, probably through a reduction in cell proliferation as a result of a rise in DNA damage and apoptosis. Oxidative stress and SOD2 also increased in response to treatment with rucaparib within the tumor cells of the treated mice. These results put the line forward to the contribution of PARP inhibitors to reduced tumor burden in lung adenocarcinoma. The potential implications of these findings should be tested in clinical settings of patients with lung tumors. Full article
(This article belongs to the Special Issue The Role of PARPs in Cancer and Aging)
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Review

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13 pages, 1579 KiB  
Review
A Double-Edged Sword: The Two Faces of PARylation
by Mincheol Kang, Seojin Park, Seong-Hoon Park, Hee Gu Lee and Jun Hong Park
Int. J. Mol. Sci. 2022, 23(17), 9826; https://doi.org/10.3390/ijms23179826 - 29 Aug 2022
Cited by 20 | Viewed by 5597
Abstract
Poly ADP-ribosylation (PARylation) is a post-translational modification process. Following the discovery of PARP-1, numerous studies have demonstrated the role of PARylation in the DNA damage and repair responses for cellular stress and DNA damage. Originally, studies on PARylation were confined to PARP-1 activation [...] Read more.
Poly ADP-ribosylation (PARylation) is a post-translational modification process. Following the discovery of PARP-1, numerous studies have demonstrated the role of PARylation in the DNA damage and repair responses for cellular stress and DNA damage. Originally, studies on PARylation were confined to PARP-1 activation in the DNA repair pathway. However, the interplay between PARylation and DNA repair suggests that PARylation is important for the efficiency and accuracy of DNA repair. PARylation has contradicting roles; however, recent evidence implicates its importance in inflammation, metabolism, and cell death. These differences might be dependent on specific cellular conditions or experimental models used, and suggest that PARylation may play two opposing roles in cellular homeostasis. Understanding the role of PARylation in cellular function is not only important for identifying novel therapeutic approaches; it is also essential for gaining insight into the mechanisms of unexplored diseases. In this review, we discuss recent reports on the role of PARylation in mediating diverse cellular functions and homeostasis, such as DNA repair, inflammation, metabolism, and cell death. Full article
(This article belongs to the Special Issue The Role of PARPs in Cancer and Aging)
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