The interplay between DNA topoisomerase 2α post-translational modifications and drug resistance.
Fiche publication
Date publication
février 2020
Journal
Cancer drug resistance (Alhambra, Calif.)
Auteurs
Membres identifiés du Cancéropôle Est :
Dr LAMOUR Valérie
Tous les auteurs :
Lotz C, Lamour V
Lien Pubmed
Résumé
The type 2 DNA topoisomerases (Top2) are conserved enzymes and biomarkers for cell proliferation. The catalytic activities of the human isoform Top2α are essential for the regulation of DNA topology during DNA replication, transcription, and chromosome segregation. Top2α is a prominent target for anti-cancer drugs and is highly regulated by post-translational modifications (PTM). Despite an increasing number of proteomic studies, the extent of PTM in cancer cells and its importance in drug response remains largely uncharacterized. In this review, we highlight the different modifications affecting the human Top2α in healthy and cancer cells, taking advantage of the structure-function information accumulated in the past decades. We also overview the regulation of Top2α by PTM, the level of PTM in cancer cells, and the resistance to therapeutic compounds targeting the Top2 enzyme. Altogether, this review underlines the importance of future studies addressing more systematically the interplay between PTM and Top2 drug resistance.
Mots clés
DNA topoisomerase, drug resistance, etoposide, post-translational modifications
Référence
Cancer Drug Resist. 2020 02 27;3(2):149-160