A New Opportunity for “Old” Molecules: Targeting PARP1 Activity through a Non-Enzymatic Mechanism
In recent years, new therapies have been developed based on molecules that target molecular mechanisms involved in both the initiation and maintenance of the oncogenic process. Among these molecules are the poly(ADP-ribose) polymerase 1 (PARP1) inhibitors. PARP1 has emerged as a target with great th...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-05-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/10/8849 |
| _version_ | 1797599782652346368 |
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| author | Pablo Iglesias Marcos Seoane Irene Golán-Cancela Máximo Fraga Victor M. Arce Jose A. Costoya |
| author_facet | Pablo Iglesias Marcos Seoane Irene Golán-Cancela Máximo Fraga Victor M. Arce Jose A. Costoya |
| author_sort | Pablo Iglesias |
| collection | DOAJ |
| description | In recent years, new therapies have been developed based on molecules that target molecular mechanisms involved in both the initiation and maintenance of the oncogenic process. Among these molecules are the poly(ADP-ribose) polymerase 1 (PARP1) inhibitors. PARP1 has emerged as a target with great therapeutic potential for some tumor types, drawing attention to this enzyme and resulting in many small molecule inhibitors of its enzymatic activity. Therefore, many PARP inhibitors are currently in clinical trials for the treatment of homologous recombination (HR)-deficient tumors, BRCA-related cancers, taking advantage of synthetic lethality. In addition, several novel cellular functions unrelated to its role in DNA repair have been described, including post-translational modification of transcription factors, or acting through protein–protein interactions as a co-activator or co-repressor of transcription. Previously, we reported that this enzyme may play a key role as a transcriptional co-activator of an important component of cell cycle regulation, the transcription factor E2F1. Here, we show that PARP inhibitors, which interfere with its activity in cell cycle regulation, perform this without affecting its enzymatic function. |
| first_indexed | 2024-03-11T03:39:14Z |
| format | Article |
| id | doaj.art-0e79acad2b77416cb81f2433b484ceb6 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T03:39:14Z |
| publishDate | 2023-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-0e79acad2b77416cb81f2433b484ceb62023-11-18T01:43:03ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-05-012410884910.3390/ijms24108849A New Opportunity for “Old” Molecules: Targeting PARP1 Activity through a Non-Enzymatic MechanismPablo Iglesias0Marcos Seoane1Irene Golán-Cancela2Máximo Fraga3Victor M. Arce4Jose A. Costoya5Molecular Oncology Laboratory MOL, Departamento de Fisioloxía, Centro Singular de Investigación en Medicina Molecular e Enfermidades Crónicas (CiMUS), Facultade de Medicina, Universidade de Santiago de Compostela and Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS), 15782 Santiago de Compostela, SpainMolecular Oncology Laboratory MOL, Departamento de Fisioloxía, Centro Singular de Investigación en Medicina Molecular e Enfermidades Crónicas (CiMUS), Facultade de Medicina, Universidade de Santiago de Compostela and Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS), 15782 Santiago de Compostela, SpainMolecular Oncology Laboratory MOL, Departamento de Fisioloxía, Centro Singular de Investigación en Medicina Molecular e Enfermidades Crónicas (CiMUS), Facultade de Medicina, Universidade de Santiago de Compostela and Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS), 15782 Santiago de Compostela, SpainDepartamento de Anatomía Patolóxica e Ciencias Forenses, Universidade de Santiago de Compostela and Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS), 15782 Santiago de Compostela, SpainMolecular Oncology Laboratory MOL, Departamento de Fisioloxía, Centro Singular de Investigación en Medicina Molecular e Enfermidades Crónicas (CiMUS), Facultade de Medicina, Universidade de Santiago de Compostela and Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS), 15782 Santiago de Compostela, SpainMolecular Oncology Laboratory MOL, Departamento de Fisioloxía, Centro Singular de Investigación en Medicina Molecular e Enfermidades Crónicas (CiMUS), Facultade de Medicina, Universidade de Santiago de Compostela and Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS), 15782 Santiago de Compostela, SpainIn recent years, new therapies have been developed based on molecules that target molecular mechanisms involved in both the initiation and maintenance of the oncogenic process. Among these molecules are the poly(ADP-ribose) polymerase 1 (PARP1) inhibitors. PARP1 has emerged as a target with great therapeutic potential for some tumor types, drawing attention to this enzyme and resulting in many small molecule inhibitors of its enzymatic activity. Therefore, many PARP inhibitors are currently in clinical trials for the treatment of homologous recombination (HR)-deficient tumors, BRCA-related cancers, taking advantage of synthetic lethality. In addition, several novel cellular functions unrelated to its role in DNA repair have been described, including post-translational modification of transcription factors, or acting through protein–protein interactions as a co-activator or co-repressor of transcription. Previously, we reported that this enzyme may play a key role as a transcriptional co-activator of an important component of cell cycle regulation, the transcription factor E2F1. Here, we show that PARP inhibitors, which interfere with its activity in cell cycle regulation, perform this without affecting its enzymatic function.https://www.mdpi.com/1422-0067/24/10/8849poly(ADP-ribose) polymerase-1PARP inhibitorsneoplasmcanceranimal disease models |
| spellingShingle | Pablo Iglesias Marcos Seoane Irene Golán-Cancela Máximo Fraga Victor M. Arce Jose A. Costoya A New Opportunity for “Old” Molecules: Targeting PARP1 Activity through a Non-Enzymatic Mechanism International Journal of Molecular Sciences poly(ADP-ribose) polymerase-1 PARP inhibitors neoplasm cancer animal disease models |
| title | A New Opportunity for “Old” Molecules: Targeting PARP1 Activity through a Non-Enzymatic Mechanism |
| title_full | A New Opportunity for “Old” Molecules: Targeting PARP1 Activity through a Non-Enzymatic Mechanism |
| title_fullStr | A New Opportunity for “Old” Molecules: Targeting PARP1 Activity through a Non-Enzymatic Mechanism |
| title_full_unstemmed | A New Opportunity for “Old” Molecules: Targeting PARP1 Activity through a Non-Enzymatic Mechanism |
| title_short | A New Opportunity for “Old” Molecules: Targeting PARP1 Activity through a Non-Enzymatic Mechanism |
| title_sort | new opportunity for old molecules targeting parp1 activity through a non enzymatic mechanism |
| topic | poly(ADP-ribose) polymerase-1 PARP inhibitors neoplasm cancer animal disease models |
| url | https://www.mdpi.com/1422-0067/24/10/8849 |
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