Fig. 6: MARK2 inhibits CHIP-dependent ubiquitination of tauC3, in part, by phosphorylating serine 416.
From: Phosphorylation of tau at a single residue inhibits binding to the E3 ubiquitin ligase, CHIP
A In vitro phosphorylation of varying tau proteoforms by MARK2. Varying tau species were incubated overnight with recombinant MARK2, and relative phosphorylation of Ser416 was visualized by western blot. Ponceau S was used as loading control. Image is representative of duplicate experiments. B In vitro ubiquitination of unmodified tauC3 or MARK2-phosphorylated tauC3 by CHIP. Samples were collected at the denoted timepoints, quenched in SDS-PAGE loading buffer, and analyzed by western blot. C Quantification of unmodified tau remaining in (B). Samples were normalized to 0-min time point and curves were fit using one-phase exponential decay (n = 3 technical replicates). D Cartoon depicting the role of tau PTMs on interactions with CHIP and shuttling to various degradation pathways.
