17May 2023
A DNA-PK phosphorylation site on MET regulates its signaling interface with the DNA damage response

A DNA-PK phosphorylation site on MET regulates its signaling interface with the DNA damage response

This study presents the characterization of a previously unreported MET RTK phosphosite, Serine 1016 (S1016), that represents a potential DDR-MET interface. Furthermore, Phosphoproteomics unveils the impact of the S1016A substitution on the overall long-term cell cycle regulation following DNA damage. Accordingly, the abrogation of this phosphosite strongly perturbs the phosphorylation of proteins involved in the cell cycle and formation of the mitotic spindle, enabling cells to bypass a G2 arrest upon irradiation and leading to entry into mitosis despite compromised genome integrity. This results in abnormal mitotic spindles and a lower proliferation rate. The current data uncover a novel signalling mechanism through which the DDR uses a growth factor receptor system for regulating and maintaining genome stability.

  • #oncology

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