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Lotz et al. Cancer Drug Resist 2020;3:149-60 I http://dx.doi.org/10.20517/cdr.2019.114 Page 157

investigations would be required to find if these positions are targeted by kinases in vivo and contribute to
the mechanism of resistance.

CONCLUSION
Most phosphorylations were found in the CTD of the Top2a isoform, related to its role in the cell cycle.
However, the conserved catalytic domains are also directly targeted by kinases and other modifying
enzymes introducing acetylations, SUMOylations, and ubiquitinations, interfering with the structure-
function properties of the Top2a isoform. Top2 PTM in cancer cells were mostly identified in targeted
studies analyzing their regulation and interactions with modifying enzymes during the cell cycle. Further
systematic analysis of Top2 PTM in cancer cells would be required to analyze the interplay between
PTM and compare their modulation in response to different compounds, in order to identify potential
biomarkers of cancer prognosis and drug resistance, as well as new therapeutic avenues targeting the Top2a
or modifying enzymes.

DECLARATIONS
Acknowledgments
We thank Robert Drillien for useful suggestions and proofreading the manuscript.

Authors’ contributions
Generated the figures: Lotz C
Wrote the manuscript: Lotz C, Lamour V

Availability of data and materials
Not applicable.

Financial support and sponsorship
This work was supported by the Fondation ARC and the grant ANR-10-LABX-0030-INRT (managed by
the Agence Nationale de la Recherche under the frame programme Investissements d’Avenir ANR-10-
IDEX-0002-02). The authors acknowledge the support and the use of resources of the French Infrastructure
for Integrated Structural Biology FRISBI ANR-10-INBS-05 and of Instruct-ERIC.

Conflicts of interest
All authors declared that there are no conflicts of interest.

Ethical approval and consent to participate
Not applicable.

Consent for publication
Not applicable.

Copyright
© The Author(s) 2020.

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