Ubiquitin‐specific protease 7 as a potential therapeutic target in dogs with hematopoietic malignancies
Aleksandra Pawlak , Joanna Bajzert , Katarzyna Bugiel , Beatriz Hernandez Suarez , Kutkowska Justyna , Andrzej Rapak , Wojciech Hildebrand , Bożena Obmińska-Mrukowicz , Raimundo Freire , Veronique A. J. Smits
AbstractBackground: Ubiquitin‐specific protease 7 (USP7) belongs to the group of deubiquitinating enzymes (DUBs), which remove ubiquitin which controls various cellular processes such as chromosome segregation, DNA repair, gene expression, protein localization, kinase activity, protein degradation, cell cycle progression, and apoptosis. It is critical for several important functions in the cell, and therefore dysregulation of USP7 can contribute to tumorigenesis. Objectives Alterations in the USP7 protein have been identified in various malignancies of humans. Our aim was to examine whether USP7 could be a potential therapeutic target in hematopoietic cancers of dogs. Methods: The expression level of USP7 in lymphocytes from healthy dogs and canine lymphoma cells was determined, and the effect of USP7 inhibition on the vital functions of canine cancer cells was examined. Results: We showed that USP7 was overexpressed in lymphomas in dogs. The USP7 inhibitor P5091 has selective cytotoxic activity in canine lymphoma and leukemia cell lines. Our results indicate that inhibition of USP7 leads to a disruption of cell cycle progression, and triggers DNA damage and apoptosis. The observed proapoptotic effect of the USP7 inhibitor most likely is not dependent on the p53 pathway. Conclusions and Clinical Importance: Our results suggest that USP7 could be explored as a potential therapeutic target in dogs with lymphoma. The effectiveness of USP7 inhibition in malignant cells is predicted to be independent of their p53 status.
|Journal series||Journal of Veterinary Internal Medicine, ISSN 0891-6640, e-ISSN 1939-1676, (N/A 200 pkt)|
|Publication size in sheets||0.5|
|Keywords in English||anticancer activity; canine hematopoietic cancers; deubiquitylases; deubiquitylases inhibitors|
|License||Journal (articles only); published final; ; with publication|
|Score||= 200.0, 28-04-2021, ArticleFromJournal|
|Publication indicators||= 0; = 1; : 2018 = 1.567; : 2019 = 2.194 (2) - 2019=2.533 (5)|
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