Jade1S acts as SUMO ligase and chaperone to steer tau oligomers to proteasomal clearance
- Jade1S, a PHD zinc finger protein at a tauopathy risk locus, binds 0N4R tau through several redundant regions and acts as a SUMO E3 ligase on tau in vitro.
- In cells, tau and Jade1S stabilize each other, while Jade1S preferentially speeds clearance of insoluble tau and leaves the soluble monomer pool largely unchanged.
- SUMO2/3-modified tau oligomers are diverted from autophagy-lysosome handling toward proteasomal degradation, and Jade1S also shows chaperone activity against induced tau oligomerization in vitro.
- Unreviewed preprint using overexpression and in vitro systems; disease relevance remains untested.
💡 Points Based on the abstract
Selective clearance of insoluble tau without touching the soluble monomer is the profile you'd want, but I wouldn't move this forward on overexpression data alone. Mutual stabilization of tau and Jade1S could just as easily trap both in aggregates. The next step is a SUMO-site mutant tau and ligase-dead Jade1S in a seeded neuron model, with endogenous-level expression.
Jade1S SUMOylates tau and targets oligomers for degradation ↗