Cargando…

Tankyrases: Structure, Function and Therapeutic Implications in Cancer

Several cellular signaling pathways are regulated by ADP-ribosylation, a posttranslational modification catalyzed by members of the ARTD superfamily. Tankyrases are distinguishable from the rest of this family by their unique domain organization, notably the sterile alpha motif responsible for oligo...

Descripción completa

Detalles Bibliográficos
Autores principales: Haikarainen, Teemu, Krauss, Stefan, Lehtiö, Lari
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Bentham Science Publishers 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4262938/
https://www.ncbi.nlm.nih.gov/pubmed/24975604
http://dx.doi.org/10.2174/1381612820666140630101525
_version_ 1782348479642730496
author Haikarainen, Teemu
Krauss, Stefan
Lehtiö, Lari
author_facet Haikarainen, Teemu
Krauss, Stefan
Lehtiö, Lari
author_sort Haikarainen, Teemu
collection PubMed
description Several cellular signaling pathways are regulated by ADP-ribosylation, a posttranslational modification catalyzed by members of the ARTD superfamily. Tankyrases are distinguishable from the rest of this family by their unique domain organization, notably the sterile alpha motif responsible for oligomerization and ankyrin repeats mediating protein-protein interactions. Tankyrases are involved in various cellular functions, such as telomere homeostasis, Wnt/β-catenin signaling, glucose metabolism, and cell cycle progression. In these processes, Tankyrases regulate the interactions and stability of target proteins by poly (ADP-ribosyl)ation. Modified proteins are subsequently recognized by the E3 ubiquitin ligase RNF146, poly-ubiquitinated and predominantly guided to 26S proteasomal degradation. Several small molecule inhibitors have been described for Tankyrases; they compete with the co-substrate NAD+ for binding to the ARTD catalytic domain. The recent, highly potent and selective inhibitors possess several properties of lead compounds and can be used for proof-of-concept studies in cancer and other Tankyrase linked diseases.
format Online
Article
Text
id pubmed-4262938
institution National Center for Biotechnology Information
language English
publishDate 2014
publisher Bentham Science Publishers
record_format MEDLINE/PubMed
spelling pubmed-42629382014-12-11 Tankyrases: Structure, Function and Therapeutic Implications in Cancer Haikarainen, Teemu Krauss, Stefan Lehtiö, Lari Curr Pharm Des Article Several cellular signaling pathways are regulated by ADP-ribosylation, a posttranslational modification catalyzed by members of the ARTD superfamily. Tankyrases are distinguishable from the rest of this family by their unique domain organization, notably the sterile alpha motif responsible for oligomerization and ankyrin repeats mediating protein-protein interactions. Tankyrases are involved in various cellular functions, such as telomere homeostasis, Wnt/β-catenin signaling, glucose metabolism, and cell cycle progression. In these processes, Tankyrases regulate the interactions and stability of target proteins by poly (ADP-ribosyl)ation. Modified proteins are subsequently recognized by the E3 ubiquitin ligase RNF146, poly-ubiquitinated and predominantly guided to 26S proteasomal degradation. Several small molecule inhibitors have been described for Tankyrases; they compete with the co-substrate NAD+ for binding to the ARTD catalytic domain. The recent, highly potent and selective inhibitors possess several properties of lead compounds and can be used for proof-of-concept studies in cancer and other Tankyrase linked diseases. Bentham Science Publishers 2014-12 2014-12 /pmc/articles/PMC4262938/ /pubmed/24975604 http://dx.doi.org/10.2174/1381612820666140630101525 Text en © 2014 Bentham Science Publishers http://creativecommons.org/licenses/by-nc/3.0/ This is an open access article licensed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.
spellingShingle Article
Haikarainen, Teemu
Krauss, Stefan
Lehtiö, Lari
Tankyrases: Structure, Function and Therapeutic Implications in Cancer
title Tankyrases: Structure, Function and Therapeutic Implications in Cancer
title_full Tankyrases: Structure, Function and Therapeutic Implications in Cancer
title_fullStr Tankyrases: Structure, Function and Therapeutic Implications in Cancer
title_full_unstemmed Tankyrases: Structure, Function and Therapeutic Implications in Cancer
title_short Tankyrases: Structure, Function and Therapeutic Implications in Cancer
title_sort tankyrases: structure, function and therapeutic implications in cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4262938/
https://www.ncbi.nlm.nih.gov/pubmed/24975604
http://dx.doi.org/10.2174/1381612820666140630101525
work_keys_str_mv AT haikarainenteemu tankyrasesstructurefunctionandtherapeuticimplicationsincancer
AT kraussstefan tankyrasesstructurefunctionandtherapeuticimplicationsincancer
AT lehtiolari tankyrasesstructurefunctionandtherapeuticimplicationsincancer