Tankyrases as modulators of pro-tumoral functions: molecular insights and therapeutic opportunities
Abstract Tankyrase 1 (TNKS1) and tankyrase 2 (TNKS2) are two homologous proteins that are gaining increasing importance due to their implication in multiple pathways and diseases such as cancer. TNKS1/2 interact with a large variety of substrates through the ankyrin (ANK) domain, which recognizes a...
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| Format: | Article |
| Language: | English |
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BMC
2021-04-01
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| Series: | Journal of Experimental & Clinical Cancer Research |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13046-021-01950-6 |
| _version_ | 1818561784591679488 |
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| author | Esteban Zamudio-Martinez Ana Belén Herrera-Campos Alberto Muñoz José Manuel Rodríguez-Vargas F. Javier Oliver |
| author_facet | Esteban Zamudio-Martinez Ana Belén Herrera-Campos Alberto Muñoz José Manuel Rodríguez-Vargas F. Javier Oliver |
| author_sort | Esteban Zamudio-Martinez |
| collection | DOAJ |
| description | Abstract Tankyrase 1 (TNKS1) and tankyrase 2 (TNKS2) are two homologous proteins that are gaining increasing importance due to their implication in multiple pathways and diseases such as cancer. TNKS1/2 interact with a large variety of substrates through the ankyrin (ANK) domain, which recognizes a sequence present in all the substrates of tankyrase, called Tankyrase Binding Motif (TBM). One of the main functions of tankyrases is the regulation of protein stability through the process of PARylation-dependent ubiquitination (PARdU). Nonetheless, there are other functions less studied that are also essential in order to understand the role of tankyrases in many pathways. In this review, we concentrate in different tankyrase substrates and we analyze in depth the biological consequences derived of their interaction with TNKS1/2. We also examine the concept of both canonical and non-canonical TBMs and finally, we focus on the information about the role of TNKS1/2 in different tumor context, along with the benefits and limitations of the current TNKS inhibitors targeting the catalytic PARP domain and the novel strategies to develop inhibitors against the ankyrin domain. Available data indicates the need for further deepening in the knowledge of tankyrases to elucidate and improve the current view of the role of these PARP family members and get inhibitors with a better therapeutic and safety profile. |
| first_indexed | 2024-12-14T00:55:16Z |
| format | Article |
| id | doaj.art-3b1e510960404a79bb244905483cb9ff |
| institution | Directory Open Access Journal |
| issn | 1756-9966 |
| language | English |
| last_indexed | 2024-12-14T00:55:16Z |
| publishDate | 2021-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Experimental & Clinical Cancer Research |
| spelling | doaj.art-3b1e510960404a79bb244905483cb9ff2022-12-21T23:23:36ZengBMCJournal of Experimental & Clinical Cancer Research1756-99662021-04-0140111510.1186/s13046-021-01950-6Tankyrases as modulators of pro-tumoral functions: molecular insights and therapeutic opportunitiesEsteban Zamudio-Martinez0Ana Belén Herrera-Campos1Alberto Muñoz2José Manuel Rodríguez-Vargas3F. Javier Oliver4Instituto de Parasitología y Biomedicina López Neyra, CSIC, CIBERONCInstituto de Parasitología y Biomedicina López Neyra, CSIC, CIBERONCCentro de Investigación Biomédica en Red de Cáncer, CIBERONCInstituto de Parasitología y Biomedicina López Neyra, CSIC, CIBERONCInstituto de Parasitología y Biomedicina López Neyra, CSIC, CIBERONCAbstract Tankyrase 1 (TNKS1) and tankyrase 2 (TNKS2) are two homologous proteins that are gaining increasing importance due to their implication in multiple pathways and diseases such as cancer. TNKS1/2 interact with a large variety of substrates through the ankyrin (ANK) domain, which recognizes a sequence present in all the substrates of tankyrase, called Tankyrase Binding Motif (TBM). One of the main functions of tankyrases is the regulation of protein stability through the process of PARylation-dependent ubiquitination (PARdU). Nonetheless, there are other functions less studied that are also essential in order to understand the role of tankyrases in many pathways. In this review, we concentrate in different tankyrase substrates and we analyze in depth the biological consequences derived of their interaction with TNKS1/2. We also examine the concept of both canonical and non-canonical TBMs and finally, we focus on the information about the role of TNKS1/2 in different tumor context, along with the benefits and limitations of the current TNKS inhibitors targeting the catalytic PARP domain and the novel strategies to develop inhibitors against the ankyrin domain. Available data indicates the need for further deepening in the knowledge of tankyrases to elucidate and improve the current view of the role of these PARP family members and get inhibitors with a better therapeutic and safety profile.https://doi.org/10.1186/s13046-021-01950-6TNKS1/2Tankyrase binding motifProteasomal degradationScaffolding functionCancerInhibitors |
| spellingShingle | Esteban Zamudio-Martinez Ana Belén Herrera-Campos Alberto Muñoz José Manuel Rodríguez-Vargas F. Javier Oliver Tankyrases as modulators of pro-tumoral functions: molecular insights and therapeutic opportunities Journal of Experimental & Clinical Cancer Research TNKS1/2 Tankyrase binding motif Proteasomal degradation Scaffolding function Cancer Inhibitors |
| title | Tankyrases as modulators of pro-tumoral functions: molecular insights and therapeutic opportunities |
| title_full | Tankyrases as modulators of pro-tumoral functions: molecular insights and therapeutic opportunities |
| title_fullStr | Tankyrases as modulators of pro-tumoral functions: molecular insights and therapeutic opportunities |
| title_full_unstemmed | Tankyrases as modulators of pro-tumoral functions: molecular insights and therapeutic opportunities |
| title_short | Tankyrases as modulators of pro-tumoral functions: molecular insights and therapeutic opportunities |
| title_sort | tankyrases as modulators of pro tumoral functions molecular insights and therapeutic opportunities |
| topic | TNKS1/2 Tankyrase binding motif Proteasomal degradation Scaffolding function Cancer Inhibitors |
| url | https://doi.org/10.1186/s13046-021-01950-6 |
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