The Krogan Lab researchers are currently performing mechanistic follow-up studies on a subset of the protein-protein interactions they identified.
“Our affinity purification mass spectrometry studies on sacsin have revealed a protein-protein
interaction with DAPK (Death-associated protein kinase)1/3, a positive mediator of gammainterferon
induced programmed cell death. Additionally, our analysis of the phosphorylation
landscape of WT and SACS-/- cell lines followed by bioinformatics analysis revealed that tau, a
known DAPK1 substrate, is differentially phosphorylated. To understand the role of sacsin in
DAPK1-mediated tau phosphorylation, we are currently overexpressing or inhibiting DAPK1. In
addition, to identify which region of the multi-domain protein sacsin is required to regulate tau
phosphorylation, we are expressing individual domains separately followed by analysis of tau
phosphorylation”.