Fig. 9: Schematic illustration of the mechanisms via which lysine methylation of PPP1CA by SUV39H2 promotes NPC senescence and IDD progression.

In normal NPCs, PPP1CA/PPP1R9B phosphatase complex binds and dephosphorylates TFEB to maintain proper autophagic activity. In degenerated NPCs, upregulated SUV39H2 interacts with and methylates lysine 141 of PPP1CA. K141 methylation of PPP1CA weakens the phosphatase activity of the PPP1CA/PPP1R9B complex that binds to TFEB, which results in decreased TFEB-regulated autophagy activity and NPC senescence.