Figure 2.

Post-translational modifications of the human Top2α. Phosphorylations and acetylations identified in the recombinant Top2α protein produced in yeast or mammalian cells are reported below the domain diagram (Bedez et al.^[16], 2018). Modifications identified in cancer cells as reported in the PhosphoSiteplus database are indicated above the domain diagrams (Horneck et al.^[40], 2014). Phosphorylation sites are colored in red, acetylation in blue, ubiquitination in yellow, and SUMOylation in green. To date, about 104 phosphorylation, 28 acetylation, 67 ubiquitination, and 15 SUMOylation sites have been identified. Twenty-six out of 29 phosphorylations in normal cells and 46 out of 75 phosphorylations in cancer cells were found in the CTD. Fifteen SUMOylation sites were identified in cancer cells, half on the DNA gate and C-gate, four in the N-gate, and five in the CTD. Thirteen acetylations on the CTD and two in the ATPase domain were reported in cancer cells. Two phosphotyrosines were identified in the N-gate, three in the DNA-gate, and one on the CTD in cancer cells. Positions are numbered as indicated in the NCBI gene ID:7153, which results in a +1 shift in the residue numbering for some positions compared with their numbering in articles (for example, Thr1342 appears in the present figure as Thr1343, and Ser1524 as Ser1525). Top2: type 2 DNA topoisomerase; CTD: C-terminal domain