Fig. 8 | Signal Transduction and Targeted Therapy

Fig. 8

From: Conversion of Ku80 K568 crotonylation to SUMOylation facilitates DNA non-homologous end joining and cancer radioresistance

Fig. 8

Proposed model for PTM conversion of Ku80 K568 from crotonylation to SUMOylation to control DNA DSBs repair and radiosensitivity. The crotonylation of Ku80 Lysine 568 (K568cr), mediated by PCAF, is decrotonylated by HDAC8 upon DNA damage, which fosters the interaction of Ku80 and DNA-PKcs and also empties the room for the subsequent SUMOylation by CBX4 E3 ligase at the same site. Failure of K568cr decrotonylation hinders Ku80 SUMOylation. Ku80 K568 SUMOylation is obligated for activating DNA-PKcs S2056 autophosphorylation to promote DNA double-strand break repair. Prevention of K568cr decrotonylation by HDAC8-specific inhibitor PCI-34051, or blockage of K568 SUMOylation by suppressing CBX4 leads to DNA-PK inactivation and defective DNA DSBs repair, which can sensitize cancer cells to radiotherapy

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